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Flashcards in SM02 Mini4 Deck (413):
1

what are the primary endocrine organs?

  • pancreas
  • hypothalamus
  • pituitary gland
  • pineal gland
  • thyroid gland
  • parathyroid glands
  • thymus
  • adrenal (suprarenal) glands
  • ovaries/testes

2

what/how is an organ defined as a primary endocrine gland?

it's primary purpose is production & release of chemical messengers that travel throughout the body

3

what defines a secondary endocrine gland?

an organ that releases chemical messengers throughout the body, but this is not its primary function

primary function is associated with another organ system

4

what are the secondary endocrine glands?

  • heart
  • stomach
  • liver
  • adipose tissue
  • kidney
  • small intestine

5

what is a transient endocrine organ?

one that is not always found in the body

only one are placenta & corpus luteum

6

structurally, what are the classes of hormones?

  1. amines: epinephrine
    • hydrophilic or hydrophobic 
  2. peptides: oxytocin
    • usually 9 aa long
    • usually hydrophilic
  3. steroids: vitamin D
    • hydrophobic
  4. prostanoids
    • derived from fatty acids
    • most are cytokines
  5. gases: NO, CO, H2S

7

what functions are the prostanoids involved in?

infalmmation, chemotaxis, pain & immunity

8

what are the signaling routes utilized by hormones?

  1. endocrine (hemocrine)
  2. paracrine
  3. autocrine
  4. neurocrine: specific, directed targeting
  5. intracrine (second messengers)
  6. intercrine (uses gap junctions)
  7. juxtacrine: ex. antigen presentation
  8. solinocrine: secreted into lumen (not blood); ex. monitor 

9

how is the endocrine system controlled?

largely by the nervous system, but some of it is under autoregulation

10

which hormones are secreted and which are stored in vesicles?

  • water-soluble amines are stored in vesicles (ex. catecholeamines)
  • lipid-soluble (steroids or gases) are produced as they are needed
    • dependent on availability of precursors
    • activation of enzyme is control point

11

what are the patterns of hormone release?

  • episodic: insulin w/food release
  • pulsatile: regularly timed short bursts; ex. cortisol
  • circadian/larger-timed rhythms: released certain times of day (or cycle); ex. GH peaks at 12am (estrogen/progesterone)

12

when does episodic release of hormone end?

when stimulus for secretion ends

13

what are the types of hormone control?

  • homeostatic feedback
    • almost always negative 
    • hormone-hormone, mineral-hormone, substrate-hormone
  • neural control
    • adrenergic, cholinergic, serotoninergic
  • chronotropic
    • pulsitile, diurnal, menstral, seasonal, & developmental rhythms

14

what processes are driven by positive feedback?

labor &parturition (oxytocin)

 

15

what is a advantage of water-soluble hormones?

usually display fast effects

ie. phosphorylation or dephosphorylation of an enzyme

16

what is the advantage of the lipid-soluble hormones?

direct regulation of gene transcription→ slow to start, but slow to stop

17

why is hormone removal so important?

hormone signaling needs to be temporary so their effects can be measured or tolerance would be accomplished by teh target cells

18

what is MCR?

metabolic clearance rate

volume of plasma cleared of a hormone per unit time, usually mL/min

inversely related to half-life

19

what are the hypothalamic hormones that exert effects on the anterior pituitary?

thyrotropin releasing hormone

gonadotropin releasing hormone

corticotropin releasing hormone

growth hormone releasing hormone

somatostatin

dopamine

20

what hormone inhibits the release of growth hormone?

somatostatin

21

what is the function of dopamine on the mammotrophs?

to inhibit the release of prolactin

22

what is the difference between a tropic and trophic hormone?

  • tropic hormone target is another gland
    • hypothalamic and anterior pituitary hormones
  • trophic hormones stimulate growth & differentiation of target tissues
    • target tissues often undergo apoptosis in the absense of trophic hormones
  • some hormones are both
    • ex. TSH

23

what are common modifiers of pulsatile secretion patterns for hypothalamic & pituitary hormones?

circadian rhythym & menstrual cycle

may experience a episodic release due to stress

24

what hypothalamic hormone controls the secretion of insulin-like growth factors by the liver?

growth hormone releasing hormone increases their secretion

somatostatin decreases release of growth hormone which decreases the secretion of insulin-like growth factors

25

how do the hypothalamic hormones signal the pituitary cells?

via GCPRs

26

what dopamine receptor is found on mammotrophs?

D2

27

how does the ultra-short feedback loop function?

autocrine action

hormone secreted by the hypothalamus gives feed back to the hypothalamus

hard to assess 

relative importance is probably very minor

28

what is the most common feedback system in teh hypothalamic-pituitary axis?

long loop

peripheral hormones inhibit release of hypothalamic & pituitary hormones

29

describe short loop feedback in hypothalamic-pituitary axis.

pituitary hormones inhibit the release of their releasing hormones from the hypothalamus

30

what hormones normally exhibit short feedback loops?

growth hormone & prolactin

31

what hormones normally exhibit ultra-short feedback loops?

very rare

only seen in pathologies at very high concentrations of hormone

32

when would ACTH provide short-loop feedback to the hypothalamus?

Addison's disease or primary adrenal insufficiency

 

33

what hormone displays a positive feedback loop?

estradiol during a certain time during the ovarian cycle stimulates release of GnRH to increase LH & FSH further increasing estradiol

34

function of prolactin

causes milk production

also inhibits gonads to temporarily reduce fertility during breastfeeding

35

effects of V1 activation

smooth muscle contraction

Gq alpha pathway: phospholipase C as second messenger→ stimulates Ca2+ mobilization

associated with vasoconstriction

"vassopressin"

36

why is V2 considered a more sensitive receptor?

because V2 is activated by much lower plasma concentrations of vasopressin/ADH than V1 is

37

effects of V2 receptor activiation

ADH action

Gs alpha pathway: adenylyl cyclase activation→ increased cAMP is second messenger

associated with water retention

38

which G alpha subunit does ADH act thru?

Gs alpha

39

where does ADH exert its effects?

distal tubule & collecting duct

40

what is the molecular effects of ADH signaling in the kidneys?

increases # of aquaporin channels in collecting duct of nephron

increases water reabsorption

41

what is the difference between central & nephrogenic diabetes insipidus?

central is the inability of the body to make ADH

nephrogenic is when the kidneys are unable to respond to ADH

both result in polyuria

42

causes of central diabetes insipidus

trauma

tumors (pituitary or that put pressure on pituitary stalk)

sx

infection

congenital

43

causes of nephrogenic diabetes insipidus

renal dz

ADH-unresponsive kidney

drug side effects (ex. lithium)

44

cause of SIADH

syndrome of inappropriate ADH secretion

excess ADH secretion from posterior pituitary

OR

another source, most commonly lung carcinomas

45

where is oxytocin produced?

paraventricular nucleus of the hypothalamus

46

what signaling pathway is utilized by oxytocin?

Gq alpha GCPR: activaition of phospholipase C→ increase in intracellular calcium

47

target tissues & effect of oxytocin

targets: smooth muscle of uterus & mammary glands

stimulates MLCK (myosin light chain kinase) for smooth muscle contraction

results in milk ejection & myometrial contractions (during labor)

48

how does oxytocin work during labor?

positive feedback loop

stretch receptors in the uterus induce increasing levels of oxytocin over time

produces more frequent & stronger contractions until delivery

49

during a lifespan, when is GH at its peak?

puberty

IGF1 increases in parallel

50

what is the function of GH & IGF during adulthood?

regulate & maintain body mass

facilitate compensory grwoth

51

during a lifespan, when does GH rapid decrease?

60

so does IGF1

52

during a day, when is GH at its peak?

around midnight

this is why children literally do grow overnight

53

what is the general pattern of release that GH follows daily?

pulsatile

also chronotropic control w/circadian rhythm

54

what can stimulate an episodic release of GH?

hypoglycemia

protein deficiency

exercise

trauma

55

describe the regulation of GH-IGF axis.

  • GH exerts short loop negative feedback
    • high [GH]→ increasing somatostatin release from hypothalamus onto pituitary
    • high [GH]→ decreased GHRH from hypothalamus to pituitary
  • IGF produced by GH target tissue, liver exerts long loop negative feedback
    • high [IGF]→ increasing somatostatin release from hypothalamus onto pituitary
    • high [IGF]→ decreased GHRH from hypothalamus to pituitary

56

what factors can inhibit GH secretion?

hyperglycemia

high levels of insulin

high levels of free fatty acids

57

why does GH decrease when plasma energy stores are high, except when those stores are amino acids?

 GH will use amino acids for protein production & growth

58

how can teh # of GH receptors at target tissues be measured?

via growth hormone binding protein

since it is a cleaved deriative of the receptor

59

why is it odd that GH has a binding protein?

becuase it is water soluble

50% is bound in plasma

free GH half life= 20', but bound= 12-16hrs

60

desribe GH signal transduction

  • 2 GH binding sites required
  • dimerization of receptor
  • activates JaK
  • second messenger: ERK1/2 & STAT

effect: increases transcription of target genes

61

GH effects on carbohydrates

increases plasma glucose

generally works in opposite direction as insulin

62

GH effects on lipids

increases plasma triglycerides

generally works in opposite direction as insulin

63

GH effects on amino acids

uptake of amino acids

increased protein synthesis & growth

decreased protein catabolism

same direction as insulin

64

GH effects on adipose tissue

simulates lipolysis

inhibits glucose uptake

65

GH effects on liver

  • stimulates
    • protein synthesis
    • gluconeogenesis
    • glycogenolysis
    • IGF production & secretion
  • inhibits
    • glycogenesis

66

GH effects on muscle

  • stimulates 
    • protein synthesis
    • amino acid uptake
    • glycogenolysis
  • inhibits
    • glucose uptake

67

what is the difference between IGF1 & IGF2?

IGF2 is more important in fetal life

68

IGF1 acts as a partial agonist on which receptor?

insulin receptor

69

what type of receptor does IGF1 bind to and what signaling pathways does it activate?

tyrosine receptor kinase

multiple pathways: SH2 (src) pathway, PI3/PIP2 pathway, SH2 pathway

70

what growth effects does IGF1 have that are different than GH?

  • in liver: none
  • in muscle:
    • protein synthesis 
    • amino acid uptake
  • in chondrocytes
    • amino acids uptake
    • protein synthesis
    • RNA/DNA synthesis
    • collagen production
    • chondroitin sulfate
    • hyperplasia
    • hypertrophy

71

what is the result of GH deficiency?

pituitary dwarfism

72

what is the result of IGF1 formation failure?

African pygmy or Leci-Lorain dwarfism

73

what are the binding affinities of the thryoid hormones for the thyroid hormone receptor?

receptor affinity for T3 is 10x higher than for T4 & 100x higher than for reverse T3

74

why do the thyroid hormone have binding proteins?

the iodine atoms do not add to hormone water solubility

they are lipid soluble

75

explain the relationship between leptin & thyroid hormones.

  • leptin secreted bu adipose tissue
  • signals PVN & arcuate nucleus
  • arcuate nucleus indirectly increases TRH secretion 
    • increases TSH release
    • increases thryoid hormone release

76

what is the body's endocrine "buffer system?"

  • increases hormone-specific globulin→ less hormone bound to albumin→ less bioavailable hormone
  • vice versa: decrease hormone specific globulin→ more hormone bound to albumin→ more bioavailable hormone

77

what is the typical fate of hormone that binds to specific hormone binding globulins?

to be metabolized in the liver

conjugated with sulfate or glucuronide & excreted as bile or urine

78

relative bioavailabilities of thyroid hormones in serum

free > albumin-bound > transthyretin >> thyroid binding globulin

79

approximately how much thyroid hormone is bound to TBG?

80% of T3

75% of T4

80

how is T4 metabolized?

  • D3= 5-deiodinase (iodine in ring closer to amino group removed)
    • forms less reactive reverse T3
  • D1/D2= 5'-deiodinase (removed iodine in ring further from amino group)
    • forms more reactive T3
  • further removal of iodines to thyronine

81

which thyroid hormone has the longest half-life?

T4

7 days

due to very tight binding to TBG

82

what are the primary effects of thyroid hormone?

increases basal metabolism

  • increases oxygen consumption
  • increases protein metabolism
  • increases carbohydrate metabolism
  • increase lipid metabolism

83

what is a permissive hormone and its effects?

a hormone that augments the action of other hormones

helps primary hormone to maintain homeostatsis

84

why does thyroid hormone cause a increase in cardiac output?

because increased metabolic rate

increases oxygen consumption and CO2 production which required high cardiac output to clear CO2 & deliver more O2

85

what is the difference between direct & indirect effect of thyroid hormone?

direct effects are effects seen in cells or organs with thyroid receptors

indirect effects are those produced by body-wide effects of thyroid hormone in cells w/o thyroid receptors

86

what are some of the main direct effects of thyroid hormone?

  • increased Na+/K+ pump activity
  • increased urea production
  • increasing beta-adrenergic receptors 
  • increasing transport capability of other hormones
    • ex. ADH

87

direct effect of thyroid hormone on adipose

  • adipose cell differentiation
  • regulates rate of lipolysis & lipogenesis
  • increases responsiveness to beta-adrenergic receptors
  • may regulate leptin production/release
  • stimulates thermogenesis in brown adipose
    • increased amt of uncoupling protein

88

what is the role of thyroid hormone in carbohydrate metabolism?

to make sure that the receptors & enzymes for all other hormones (insulin, glucagon, cortisol, etc) are made, placed, & ready to activate

89

where is insulin secreted from & to?

by beta cells in the islets of Langerhans of the pancreas

into the venous blood of portal circulation

90

describe the insulin secretion pathway.

  • glucose enters beta cells via GLUT2 on arterial membrane
  • metabolism of glucose increases ATP & NADH levels
  • K+ channels close (ATP ligand gated) & Ca2+ channels open
    • depolarizes cell
  • Ca2+ binds transport proteins  for exocytosis of insulin

91

what other energy sources increase beta cell ATP levels?

fatty acids

leucine

arginine

92

how does parasympathetic nervous activation modulate insulin secretion?

  • ACh release
  • activates phospholipase C via Gq alpha
  • increases IP3/DAG
  • increases Ca2+ & protein kinase C
  • induces insulin release

93

how does cholecystokinin modulate insulin secretion?

  • activates phospholipase C via Gq alpha
  • increases IP3/DAG
  • increases Ca2+ & protein kinase C
  • induces insulin release

94

how does sympathetic activity module insulin secretion?

  • norepinephrine released
  • acts via alpha-adrenergic receptors
  • activates Gi alpha
  • decreases cAMP levels 
  • inhibits insulin secretion

95

how does somatostatin modulate insulin secretion?

  • activates Gi alpha
  • decreases cAMP levels 
  • inhibits insulin secretion

96

what substances increase cAMP pathway to stimulate insulin secretion?

glucagon

GLP-1

beta-adrenergic agonists (epinephrine, higher affinity here thus activated at lower plasma concentration)

97

what downstream molecules lead to insulin release?

protein kinase A

protein kinase C

Ca2+

98

what are the main factors in blood that stimulate insulin secretion?

inceased glucose

increased amino acids (especially arginine & leucine)

GI hormones (GLP-1: glucagon-like peptide 1)

99

why does insulin not increase as much when glucose is administered parenterally compared to orally?

incretins: class of GI-secreted hormones w/beta cells as their target (prime beta cells when food is in GI tract), such as...

primarily glucose-dependent insulinotropic polypeptide (GIP)

glucagon-like peptide 1

100

main function of the male reproductive system

germ cell (sperm) production & maturation

101

endocrine functions of male reproductive system

  • embryonic sexual differentiation
  • development of male internal & external genitalia
  • spermatogenesis
  • male secondary sex characteristics
  • control fo male reproductive neuroendocrine axis
  • sexuality
  • libido
  • erection

102

where are LH receptors found in males?

on Leydig cells

103

function of Leydig cells

produce testosterone

104

where are FSH receptors found in males?

on Sertoli cells

105

function of Sertoli cells

provide support for germ cell development

  • support spermatogonia
  • form blood-testes barrier
  • secrete Mullerian inhibiting substance (MIS)
  • secrete inhibin B
  • androgen binding protein production

106

what is the effect of LSH binding in Sertoli cells?

spermatogenesis & inhibin B secretion

107

function of inhibin B

peptide hormone

enters circulation

acts on anterior pituitary to inhibit FSH secretion

108

what is the effect of LH binding on Leydig cells?

testosterone secretion

enters circulation

acts on anterior pituitary to inhibit LH release

109

describe the hypothalamic-pituitary-testicular axis.

  • hypothalamus releases GnRH
  • GnRH stimulates release of LH & FSH from gonadotrophs in anterior pituitary
  • FSH acts on Sertoli cells to stimulate spermatogenesis & inhibin B secretion
    • Inhibin B enters circulation
    • inhibits release of LH from anterior pituitary
  • LH acts on Leydig cells to stimulate testosterone secretion
    • testosterone, DHT, & estrogen inhibit LH release from anterior pituitary
    • testosterone, DHT, & estrogen inhibit GnRH release from hypothalamus

110

where is GnRH secreted from?

arcuate & preoptic nuclei of hypothalamus

111

what signal transduction pathway is utilized by GnRH binding to gonadotrophs?

Gq alpha GCPR

  • activation of phospholipase C
  • hydrolyzes PIP2 into IP3 & DAG
  • DAG activates protein kinase C (PKC)
  • PKC phosphorylates transcription factors & stimulates LH & FSH transcription
  • IP3 stimulates Ca2+ release from ER
  • Ca2+ stimulates exocytosis of gonadotropins

112

what signaling pathway is utilized by LH hormone in Leydig cells? 

Gs alpha GCPR

  • activation of adenylate cyclase 
  • increased cAMP activates protein kinase A
  • phosphorylates substrate proteins that simtulate gene transcription of testicular growth & development, steroidogenesis, & protein synthesis

common signal transduction pathway for FSH, hCG, & TSH

113

describe the structure of the gonadotropins

alpha & beta subunits

alpha subunit is common

beta subunit confers hormone specificity & function

114

what secretion pattern does GnRH follow?

pulsatile

approximately every 90-120 minutes in adult males

115

what are the modulators of GnRH secretion?

  • normal negative feedback
    • testosterone
    • estrogen
    • DHT
  • others
    • leptin stimulates GnRH release
    • prolactin inhibits GnRH release

116

how does GnRH pulsation determine gonadotropin release?

frequent release of GnRH leads to increased LH & decreased FSH release

less frequent release of GnRH leads to decreased LH & increased FSH release

117

how is LH inhibition mediated?

decreased gonadotropin-specific beta-subunit synthesis in the anterior pituitary

118

what is normal testicular size?

4.1-5.2 cm in length

2.5-3.3 cm in width

119

where is aromatase found in males?

aka CYP19

Sertoli cells

converts androgens to estrogens

also found in adipose, skin, & muscle

120

where is 5-alpha reductase found?

Sertoli cells

responsible for conversion of testosterone to DHT

also found in urogenital tract, skin, hair follicles, & liver

121

why would an inhibin B level be used for?

index of Sertoli cell fucntion & spermatogenesis

increased inhibin B correlates to increased total sperm count & testicular volume

122

what is inhibin A?

heterodimer glycoprotein

shares same alpha subunit as inhibin B

unknown role in males

123

cryptorchidism

incomplete descent of testes from abdominal cavity

effects:

  • impaired spermatogenesis
  • if bilateral
    • decreased testosterone
    • decreased inhibin B
    • increased LH
    • increased FSH

124

what happens to testosterone that diffuses across the blood-testes barrier?

enters Sertoli cells and binds nuclear androgen receptor

regulates spermatogenesis

or gets metabolized to DHT or estradiol

125

where does the majority of plasma hormone levels come from in males?

  • testosterone→ testes
  • DHT→ peripheral conversion of precursors (mostly skin, but also liver, hair follicles, urogenital tact)
  • estrdiol (E2)→ peripheral conversion of precursors (adipose, skin, muscle)
  • estrone (E1)→ peripheral conversion of precursors
  • dehydroepiandrosterone sulfate (DHEAS)→ adrenal secretion

126

what serum proteins bind testosterone and their affinity?

sex hormone binding globulin→ binds 44% of circulating testosterone

albumin: 1000x low affinity→ binds 54% of testosterone in circulation

127

where is androgen binding protein found?

only in Sertoli cells

it is not secreted into circulation→ creates reservoir of testosterone & keeps it in the cell (since it is a steroid that would otherwise freely diffuse out of the cell)

128

why does albumin bind more testosterone in circulation than SHBG?

b/c albumin is plasma concentration is so much high than SHBG

129

what is the relative binding affinities for SHBG's different ligands?

DHT> testosterone> androstenedione> estradiol> estrone

130

what is the fate of hormones bound to SHBG?

liver metabolism

followed by excretion in bile

OR

conjugation to glucuronide or sulfate, returned to circulation, & excreted in urine

131

where is SHBG produced?

liver

132

how is SHBG production influenced by the sex hormones?

increased by estrogens

decreased by testosterone

thus higher levels are normal in women & seen in hypogonadal men

lower levels found in hypothyroidism, obesity, & acromegaly

133

why must DHT be converted in its target tissue to exert its effects?

b/c SHBG binding affinity for DHT is so high in circulation that is almost completely unavailable

134

role of testosterone in fetal life

differentiation of fetal genitourinary tract

masculinization of male genitalia

135

role of testosterone at puberty

development of male genitalia

initiation of spermatogenesis

136

role of testosterone in adulthood

stimulates & maintains muscle mass accumulation

sustains spermatogenesis

drives male libido

137

what happens to testosterone with age?

declines 1% per year after age 30

and more steeply after 60yo

resulting in loss of libido, reduced muscle and bone mass

138

other than adolescence & elderly when does male testosterone levels decline?

at parturition

139

where are AR & ER found?

adrogen & estrogen receptors

bound to heat shock proteins in the cytosol

140

function of DHT

  • embryonic development of scrotum, penial urethra, & prostate
  • prostate differentiation & growth
    • secretion of PSA
  • pubertal development of facial, pubic, & underarm hair
  • pubertal penis growth
  • pubertal differentiation & activation of prostate
  • sebaceous gland activity
  • male-pattern hair-growth & balding

141

estradiol function in males

  • feedback regulation of LH secretion
  • bone growth & epiphyseal closure
  • brain masculinization & sexual behavior
  • regulation of fluid in ejaculate

142

direct actions of testosterone in males

  • embryonic development of Wolffian duct-derived structures
  • pubertal growth of penis, testes, larynx (deepening of voice)
  • spermatogenesis
  • anabolic effects on skeletal muscle & erythropoiesis
  • libido & erectile function
  • inhibits breast developmen
  • stimulates aggressive behavior
  • increases VLDL & LDL
  • increases central obesity

143

can testosterone administration to adult males increase penis size?

NO

the penis does not express androgen receptor after puberty

144

what is the effect of loss of action of estradiol action on the ERalpha in males?

normal binding and downstream action results in 90% of fluid reabsorption in rete testes

loss of this action leads to defective reabsorption & infertility

145

why does gonadotropin secretion steeply decline after midgestation?

b/c the male fetus has synthesized measureable amounts of testosterone to inact normal negative feedback

146

why are adolescent levels of the gonadotropins low in males?

unknown mechanism

may involve CNS restraint in GnRH secretion

147

what marks gonadarche?

testes enlargement

148

what is adrenarche?

1-2 years before puberty in males

rise in adrenal DHEA, DHEAS, & androstenedione

149

pubarche

pubic hair growth

150

spermarche

initiation of spermatogenesis

151

what defines percocious puberty?

puberty beginning before 9 in boy & before 6-8 in girls

152

Tanner Stages of development for males

  1. preadolescent: testes, scrotum & penis are approx. same size & no pubic hair
  2. scrotum & testes enlargement w/some scrotal reddening; no penial enlargement; sparse pubic hair growth (base of penis)
  3. penis growth; further growth of testes & scrotum; hair becomes darker, coarser & curlier
  4. development of glans; scrotal skin has darkened; hair is adult type
  5. adult genitalia in size & shape; hair spread to medial surface of thighs

153

how does SHBG level change with age in males?

increases

thus enhancing the effect of the already decreased levels of testosterone

154

primary hypogonadism

testicular dysfunction

155

secondary hypogonadism

hypothalamic/pituitary dysfunction

156

effects of hypogonadism in male fetus

ambiguity of genitalia

157

effects of hypogonadism in pubescent males

poor secondary sexual development

158

effects of hypogonadism in adult males

  • reduced libido
  • erectile dysfunction
  • muscle atrophy
  • infertility

159

causes of primary hypogonadism in males

impaired testicular development

gonadal dysgenesis

crytorchidism

enzyme defects in testosterone biosynthesis

LH receptor defects

testicular damage

160

causes of secondary hypogonadism

Kallmann syndrome: genetic disorder characterized by failure of GnRH secreting neurons to migrate to hypthalamus→ reduced GnRH→ delayed or absent puberty

mutated GnRH receptor

pituitary tumor

trauma

sx

hyperprolactinemia: inhibits GnRH release

161

pathological causes of male gynecomastia

  • androgen deificency: estrogen form adrenals
  • androgen insensitivity
  • increased estrgen production: Sertoli cell tumor
  • increased androgen to estrogen conversion: increased levels of aromatase
  • drug side effect

162

biochemical cause of male gynecomastia

decrease in androgen to estrogen ratio

163

presentation of androgen insensitivity syndrome

amenorrhea

no pubic or axillary hair

blind vaginal pouch/no uterus or cervix

undescended teses

elevated testosterone, DHT, estrogen, & LH 

may also present pre-puberty w/testis-like mass in inguinal canal or labia

**genetic male that develops as phenotypic female**

164

tx of complete androgen insensitivity syndrome

testes removal

estrogen therapy to prevent osteoporosis

165

presentation of 5alpha-reductase deficiency

ambiguous or female genitalia at birth

"penis at 12" due to increased testosterone at puberty

may have blind vaginal pouch

elevated testosterone to DHT ratio

**autosomal recessive⇒ very rare**

166

tx of 5alpha-reductase deficiency

gender reassignment sx

followed by hormone replacement therapy for chosen sex

167

causes of androgen excess

hypothalamic tumor

androgen producing tumors

adrenal hyperandrogenism

anabolic steroid use

168

why is does anabolic steroid used cause testicular atrophy?

because anabolic steroids inhibit the release of LH & FSH via negative feedback

w/o FSH, Sertoli cells do not produce androgen binding protein (ABP) to retain testosterone in the cell for spermatogenesis & testicular growth/maintenance

169

alopecia is less common in males of what descent?

Asian & African-American

170

name two medical problems that 5-alpha reductase inhibitors are used to treat.

alopecia & benign prostatic hyperplasia

171

tx of precocious puberty

GnRH

constant GnRH stimulation leads to downregulation of GnRH receptors→ reduced LH & FSH secretion

172

173

what hormones are highest during the follicular phase of the mestrual cycle?

FSH & estrogen 

174

what hormones are highest during the luteal phase of menstrual cycles?

progesterone & mildly LH

175

what hormone triggers ovulation?

LH

w/a midcycle peak

176

describe the hypothalamic-pituitary-ovary axis.

  • hypothalamus stimulates pituitary w/GnRH
  • pituitary releases LH & FSH
  • ovary stimulated by LH & FSH releases estradiol, progesterone, inhibin, & testosterone
  • estradiol (E2), progesterone, & inhibin negatively feedback on hypothalamus & pituitary to inhibit release of GnRH and FSH & LH respecitvely
    • testosterone does NOT feedback in females
    • E2 also has + feedback mechanism

177

in females, what signal tranduction pathway is activated by GnRH binding?

Phospholipase C

PIP2→ IP3 + DAG

178

in females, what signal transduction pathway is activated by FSH binding?

Gs alpha

increases cAMP

protein kinase A activation

179

in females, what signal transduction pathway is actived by LH binding?

Gs alpha

increases cAMP

protein kinase A activation

180

what modulators decrease GnRH pulsation?

  • low levels of estrogen
  • progesterone
  • CRH (corticotropin-releasing hormone)
  • endorphins
  • dopamine
  • prolactin

181

what modulators increase GnRH pulsation?

  • high levels of estrogen
    • positive feedback that lead to high levels of LH pre-ovulation
  • kisspeptin
  • leptin

182

what is the proposed link between puberty & obesity in females?

increased leptin release from adipose

leptin enhances GnRH pulsatile release

early onset of FSH & LH release

causing early onset of puberty

183

what is kisspeptin?

polypeptide secreted from kisspeptin neurons in arcuate nucleus of hypothalamus

184

what effects kisspeptin expression?

leptin

thus when leptin is low, so is kisspeptin

may help explain decreased fertility in hypoleptinemia & underweight females

185

high frequency, low amplitude GnRH pulsation stimulates the anterior pituitary to release?

LH

approximately every 60'

186

low frequency, high amplitude GnRH pulsation stimulates gonadotrophs to release?

FSH

approximately every 200' (3+ hrs)

187

during what part of the cycle is FSH release favored over LH release?

late luteal phase

critical for initiation of follicular recruitment during early follicular phase of next cycle

188

during what phase does high level of estrogen exhibit positive feedback on teh hypothalamus & pituitary?

late follicular phase ONLY

189

primordial follicles grow into primary follicles on their own schedule because?

they are not dependent on gonadotropins

190

what are the types of granulosar cells found in a Graafian follicle?

  • cumulus: surround the oocyte
    • cumulus oophorus: oocyte & surrounding cells that project into the antrum
  • mural: surround the antrum

191

how long does it take a primordial follicle to become a primary follicle?

150 days after recruitment into frowing pool

192

how long does it take a primary (unilaminar) follicle to become a secondary (mulitlaminar) follicle?

120 days

193

how long is the typical antral stage of follicular development?

60 days

194

how long does it take an antral follicle to become a Graafian follicle?

about 10 days for dominant follicle selection from cohort (others undergo atresia)

additional 10 day maturation before ovulation

 

195

function of FSH in females

stimulates ovarian follicle growth

required for ovarian hormone synthesis & secretion

196

function of LH in females

stimluates ovulation

formation of corpus luteum

required for ovarian hormone synthesis & secretion

197

describe the secretion & function of inhibin B in females.

  • secreted by granulosa cells of small antral follicles
  • during follicular phase
  • production & secretion stimulated by FSH
  • inhibits pituitary FSH synthesis & secretion

198

describe the secretion & function of inhibin A in females.

  • secreted by granulosa luteal cells of corpus luteum
  • production & secretion stimulated by LH 
  • during luteal phase
  • inhibits pituitary FSH synthesis & secretion

199

what cells secrete AMH?

anti-Mullerian hormone aka Mullerian inhibiting substance

granulosa cells of antral follicles

200

what is serum AMH used for?

marker of ovarian reserve & reproductive lifespan

proportional to # of developing follicles in ovaries (decreases over reproductive life)

201

which ovarian cells produce estrogens?

granulosa cells produce estrone & estradiol

b/c they have CYP19 & theca cells do not

202

which ovarian cells produce progesterone?

theca & granulosa cells

203

how does the shift from the delta5 hormone synthesis pathway to delta4 pathway make a difference when they both lead to the same end products?

theca cells complete delta5 which leads to DHEA→ androstenedione→ testosterone

theca luteal cells complete delta4 pathway which produces progesterone along the way→ progesterone is important/main hormone of luteal phase

204

how is progesterone increased during the luteal phase of menstruation?

  1. theca cells→ theca luteal cells
    • delta5 hormone synthesis pathway→ delta4
  2. 3beta-HSD (hydroxysteroid dehydrogenase) upregulation in granulosa luteal cells

205

what enzyme do theca cells lack for estrogen synthesis?

aromatase (CYP19)

theca cells cannot convert androstenedione to estrone or testosterone to estradiol

206

what enzyme do granulosa cells lack for estrogen synthesis directly from cholesterol?

CYP17 (w/17alpha hydroxylase & 17-20-lyase activity)

granulosa cells cannot convert pregnenolone to DHEA

207

which receptors are found on theca cells?

LHR

208

which receptors are found on granulosa cells?

LHR & FSHR

209

what hormone stimulates androgen production in the ovaries?

LH

210

what hormone stimulates estrogen production in the ovaries?

FSH

211

what are the downstream effects of FSH binding on granulosa cells?

  • stimulation of granulosa cell mitosis
  • antrum formation
    • via follicular fluid formation
  • inhibin B production & secretion
  • upregulation of aromatase & 17beta-HSD (hydroxysteroid dehydrogenase)
    • enhances estradiol synthesis

212

what is the product of luteinization?

corpus luteum formation from ruptured follicle post ovulation

213

how is the rich vascular network formed in the corpus luteum?

granulosa cells release VEGF under the control of LH

214

why is corpus luteum vascularization important?

because it needs to survive as it is the main producer of progesterone during the luteal phase of mestruation

if conception occurs, it will survive longer under direction of hCG as continued progesterone is needed in early pregnancy until the placenta starts to make it

215

how long does the average corpus luteum survive before luteolysis?

14 days +/- 2days

216

how do granulosa cells change after ovulation?

  • become granulosa luteal cells
  • grow much larger
  • increased levels of StAR, P450scc, 3beta-HSD, & aromatase enzymes
    • high capacity for progesterone & estrogen production

217

how do theca cells change after ovulation?

  • become theca luteal cells
    • smaller than GLCs
  • strongly express androgen biosynthetic pathway enzymes
  • change from delta5 to delta4 hormone synthesis pathway
    • higher production of progesterone

218

how is DHEAS converted?

DHEAS is converted to DHEA

by sulfatase

found in adrenals, liver, & small intestine

219

what fates does androstenedione have? and how?

  • testosterone
    • via 17beta-HSD
    • skin & adipose
  • estrone
    • CYP19
    • adipose, skin, bone, & brain

220

what fates does testosterone have in females? how?

  • estradiol
    • CYP19
    • granulosa cells of ovarian follicles, adipose, skin, bone, & brain
  • DHT 
    • 5-alpha reductase
    • skin

221

DHEAS is produced solely in?

adrenals

222

where is the AR found in females?

adipose, skin, placenta, CV system, bone, brain, GU tract, GI tract, & skeletal muscle

223

physiological functions of androgens in females

substrate for estrogen synthesis in utero, reproductive life, menopause

adrenache (pre-pubertal maturation of adrenals)

pubarche (development of pubiv hair, axillary hair, & adult sweat glands)

224

in females, what factors increase SHBG?

estrogen

pregnancy

hyperthyroidism

225

in females, what factors decrease SHBG?

androgens

obesity

hypothyroidism

glucocorticoid excess

high insulin

high GH

high prolactin

226

causes of Hirsutism

  • excess adrenal or ovarian androgen secretion
  • decreased SHBG
    • increases testosterone bioavailability
      • high insulin
      • high GH
      • high androgens
      • high prolactin
      • hypothyroidism
      • obesity

227

how is PCOS characterized?

PCOS= polycystic ovarian syndrome

hyperandrogenemia (over secretion og androgens by theca cells)

polycystic ovaries (many follicles arrested in antral stage

little to no ovulation→ no peak in estrogen levels to stimulate ovulation

228

how is the origin of androgen excess determined?

testosterone created by both adrenals & ovaries

DHEAS only by adrenal→ plasma levels elevated if adrenal origin

229

where is estriol produced?

by the placenta

and periphery form esterone

230

when is estrone produced?

menopause

231

where is estradiol produced?

granulosa cells

corpus luteum

peripheral conversion of testosterone

232

when is estriol secreted?

pregnancy

233

when is estradiol secreted?

reproductive life

234

how is estriol synthesized?

metabolite of estrone

via 17beta-HSD

235

how is estradiol synthesized?

aromatization of testosterone

236

how is estrone synthesized?

peripheral conversion fo estradiol

by 17beta-HSD

or aromatization of androstenedione

237

where is estrone produced?

adipose

skin

granulosa cells

238

which estrogen is mos abundant is in urine?

estriol

b/c it is a metabolite of estrone & weakest estrogen (very little binding to receptor)

239

why is circulation estrogen typically bound to albumin instead of SHBG?

because it has a lower binding affinity to SHBG than the androgens

240

where is the ERalpha found?

reproductive organs

cytosolic & nuclear

241

where is ERbeta found?

granulosa cells & non-reproductive organs

cytosolic & nuclear

242

estrogen effects on breasts

proliferation of mammary ducts

prigmentation of areolas

243

estrogen effects on cervix

thin, non-viscous, elastic, alkaline mucus secretion

244

effects of estrogen on uterus

increases VEGF→ increase angiogenesis

245

effects of estrogen on endometrium

proliferation, thickening, lengthening of uterine glands

increases expression of ERalpha & progesterone receptor

246

effects of estrogen on myometrium

increases contractility

increases responsiveness to oxytocin

247

effects of estrogen on Fallopian tubes

increases # of ciliated & secretory cells

increases rate of ciliary beating for egg transport

increases tubal secretions for sperm transport

248

effects of estrogen on vagina

cornification & accumuluation ofglycogen in epithelium

increases vaginal secretion w/high pH

249

what is the effect of chronic high estrogen exposure on the endometrium?

hypertrophy & hyperplasia

may progress to endometrial cancer if unopposed by progesterone

250

what causes premenstrual bloating?

estrogen stimulates Na+ reabsorption in the kidneys

causes water retention

251

effects of estrogen on bones

increases osteoblasts

decreases osteoclast formation & activity

preserves bone density

leads to epiphyseal closure

252

why are estrogens considered vasodilatory?

increase local release of NO, prostaglandin E2, & prostacyclin

decrease production or activity of endothelin 1 (vasoconstrictor)

253

symptoms of estrogen deficiency

  • vaginal atrophy
  • hot flashes
  • reduced libido
  • dyspareunia: difficult or painful sex
  • decreased bone density
  • osteoporosis
  • decreased endometrial proliferation
  • increased CV risk
  • increased LH & FSH: due to decreased negative feedback

254

causes of estrogen deficiency

  • menopause
  • premature ovarian failure
  • reduced pituitary/hypothalamic stimulation

255

causes of excess estrogen

  • obesity
  • ovarian tumor
  • exogenous estrogen

256

symptoms of excess estrogen

  • increased endometrial proliferation
  • increased venous thrombosmebolic events
  • increased risk of endometrial & breast cancer
  • decreased LH & FSH: due to strong negative feedback

257

why aren't menopausal women treated with estrogen?

b/c estrogen replacement therapy can lead to increased risk of breast & uterine cancers

258

how is progesterone synthesized?

from pregnenolone

by 3beta-HSD

259

how is progesterone biosynthesis controlled?

LH causes an upregulation of expression & activity of enzymes needed for progesterone synthesis

namely: StAR, CYP11A1, & 3beta-HSD

in corpus luteum

260

where is the progesterone receptor found?

uterus

Fallopian tubes

Kisspeptin neurons

gonadotrops

breast

brain

adipose

261

what compound is produced by the corpus luteum but not the placenta?

17alpha-hydroxyprogesterone (another progestogen)

less potent than progesterone, but measureable

262

other than albumin, what plasma binding protein may carry progesterone?

cortisol-binding globulin

263

effects of progesterone on the brain

negative feedback on hypothalamus & pituitary

increases body temperature (approx. 0.5ºF)

264

effects of progesterone on breasts

stimulates growth of lobules & alveoli

pre-menstrual breast tenderness

265

effects of progesterone on myometrium

decreases Ca2+ uptake→ decreases contractility

266

effect of progesterone on endometrium

  • increases vascularization (extension of spiral arteries)
  • increases coiling & toruosity of glands
  • increases gland secretions
  • stromal edema & differentiation

267

effects of progesterone on Fallopian tubes

increases ciliary beating in direction of uterus

increases tubal secretions for nourishment of embryo

268

effects of progesterone on vagina

decrease of epithelial cornification

decrease in vaginal secretions w/low pH→ stops late fertilization

269

effects of progesterone on cervix

thick, non-elastic, tenacious, viscous cellular cervical mucus secretion→ stops late fertilization

270

when does cervical mucus form a fern-pattern when dried on a glass slide?

when it is under estrogen stimulation

mostly around the time of ovulation

271

what is the size of a follicular cohort predictive of? 

ovarian reserve or PCOS

272

when are preantral follicles recruited?

during the late luteal phase of the cycle 3 before ovulation

273

when is the dominant follicle selected?

late luteal phase of menstrual cycle 3 to be ovulated in the following cycle

274

what stimulates menstruation?

withdrawl of progesterone

275

progesterone withdrawl mechanism of stimulating menses

  • 24hrs before menses, progesterone withdrawl
  • induces release of extracellular matrix degrading enzymes & vasoconstrictive substances 
    • matrix metalloproteinases (MMPs) & prostaglandins (PGs)
  • vasoconstriction→ ischemia & necrosis in spiral arteries & endometrium
  • necrotic blood vessels rupture→ hemorrhages grow over 24-36hrs
  • necrotic endometrial tissue separates from uterus
  • desquamated tissue & blood stimulate uterine contractions→ expel uterine contents

276

why is menstrual fluid usually non-clotting?

release of fibrinolysin

277

what are the ovarian causes of amenorrhea?

PCOS (increased androgen, estrogen & LH)

depletiono of follicles (estrogen deficient, increases LH & FSH)

278

pituitary cause of amenorrhea

hyperprolactinema (30% of cases)

increased prolactin is inhibiting GnRH, LH, & FSH

279

metrorrhagia

intermenstrual uterine bleeding

280

menometrorrhagia

heavy, prolonged, irregular bleeding at frequent irregular intervals

causes: hormonal imbalance, endometriosis, cancer

281

polymenorrhea

frequent, regular episodes of uterine bleeding at intervals less than 21 days

282

oligomenorrhea

infrequent or irregular bleeding occurring at prolonged intervals greater than 35 days

283

what reactives GnRH release during puberty?

mechanism unknown, but appears to involve reduced sensitivity to steroid negative feedback

decreased GABA inhibition, increased glutamate expression, & increased kisspeptin expression

284

thalarche

breast bud development

285

Tanner Stages in females

  1. preadolescent: elevation of papilla; no pubic hair
  2. breast bud development; long downy pubic hair near labia
  3. enlargement of breasts; increase in amt & picment of pubic hair
  4. areola & nipple for secondary mound above breast; pubic hair is adult in type not distribution
  5. large breasts w/single contour; adult pubic hair type & distribution

286

what is the most clinically relevant hormone to measure for identification of menopause?

FSH

measured at during early follicluar phase of menstrual cycle

>2 standard deviations about the mean is a marker of impending menopause

287

what changes occur to the endometrium in preparation for receipt of a fertilized egg during the luteal phase of the menstrual cycle?

estradiol promotes:

  • growth & repair of luminal epithelium
  • induces expression of progesterone receptor
  • stimluates stromal & glandular epithelial cell proliferation
  • blood vessel elongation
  • growth of tubular glands

288

during the periovulatory period, increased estrogen levels lead to a surge in which hormones?

gonadotropins (LH & FSH)

due to positive feedback of estradiol at this time

289

at what stage of the menstrual cycle is a dominant follicle selscted to become the follicle that will be ovulated?

late luteal stage of preceeding cycle

290

which enzyme is primarily responsible for sperm penetration of the zona pellucida?

acrosin

released from acrosome upon SP recptor binding to ZP3 of zona pellucida

291

what is the time between the onset of the luteal phase of the menstural cycle and the onset of menses?

14 days

luteal phase is not as variable as the follicular phase

292

what cause basal body temperature to increase during the luteal phase of menstrual?

progesterone acting on the hypothalamus

293

how does the consistency of the cervical mucus change during the periovulatory period?

it becomes tinner

allows sperm easier passage for fertilization

294

where in the Fallopian tube does fertilization occur?

ampulla

295

where does the majority of sperm attrition occur?

vagina

94% lost to leakage

296

what effect does prolactin have on ovulation?

suppresses it

297

What is the primary enzyme released during the acrosome reaction?

acrosin

298

what is the zona pellucida protein to which sperm binds before the acrosome reaction?

ZP3

299

What makes a dominant follicle dominant?

exact mechanism is unknown

  1. high rate of granulosa cell mitosis
  2. enhanced vascular system
    • permits enhanced delivery of  FSH
  3. more FSH receptors 
    • responds more strongly to FSH
  4. increased aromase activity
  5. enhanced estradiol secretion

300

what is the primary function of matrix metalloproteinases in ovulation?

breakdown of collagen in basement membrane & theca externa for follicular rupture

301

Which granulosa cells produce progesterone and express LH receptors for the first time immediately prior to ovulation? What hormone is responsible?

mural granulosa cell: on basal lamina, most external layer from ooctye

FSH produces this change

302

Which enzyme is primarily responsible for penetration of cumulus cells?

hyaluronase

303

Many women experience lower abdominal & pelvic pain midway through their menstrual cycle. What is the name of this process?

Mittelschmerz

304

What is primary amenorrhea?

 failure of menses to occur by age 16 years, in the presence of normal growth and secondary sexual characteristics

305

What is secondary amenorrhea?

absence of menstrual bleeding in a woman who had been menstruating but stops menstruating for 3+ months in absence of pregnancy, lactation, cycle suppression with systemic hormonal contraceptive pills, or menopause

306

What is the revelance of polyspermy block?

prevents trichromy

prevents two sperm from fertilizing the same egg

307

What is the relevance of sperm hyperactivation?

increases motility

helps sperm reach follicle & through the cumulus cells to the oocyte

308

In what way could administration of inhibitors of prostaglandin synthesis affect ovulation?

NSAIDs, prostaglandin synthase inhibitors, COX2 inhibitors, MMP inhibitors, VEGF inhibitors may inhibit ovulation

b/c PGE2 activates plasminogen activator & determines site of stigma and PGF2alpha is involved in stigma formation & ovarian smooth muscle contraction during oocyte expulsion

309

Which hormone is responsible for oocyte meiosis resumption at ovulation?

LH

  • acts on mural granulosa cells
  • increased EGF-like factors 
  • factors act on cumulus cells to close gap junctions to oocyte
  • decreased cGMP
  • increases phosphodiesterase activity
  • decreases cAMP levels
  • decreases protein kinase A activity
  • activates MPF (Maturation Promoting Factor)
  • resumption of meiosis

310

main steps of ovulation

  1. dominant follicle selection
  2. increased estradiol secretion & + feedback to HP axis
  3. gonadotropin surge: LH & FSH
  4. resumption of meiosis in oocyte
  5. cumulus cell expansion
  6. breakdown of follicle wall
  7. oocyte release

311

how long is the cumulus oocyte complex viable for fertilization?

12-24 hrs

312

how does increased estradiol of the dominant follicle lead to atresia in the other follicles of the cohort?

  • increases estradiol 
  • - feeback on HP axis
  • decreased FSH
  • causes subordinate follicles can no longer support growth​
    • increased FSHR on dominant follicle
  • subordinate follicles undergo atresia

313

what is responsible for shutting off granulosa cells mitosis? and when does this occur?

preovulatory LH surge

314

when does estradiol + feeback occur?

48-96 hrs before ovulation (induces it)

315

when does the gonadotropin surge occur?

30-36 ours prior to ovulation

LH peak is 10-12hrs before ovulation

316

what occurs in the follicle in response to the gonadotropin surge?

meiosis resumption

 cumulus cell expansion

follicle wall breakdown

317

primary oocytes are arrested in....

prophase of meiosis I

318

how are primary oocytes arrested?

  • constitutively active cAMP producing GCPR in oocytes
  • phosphodiesterase in oocyte to inactivate cAMP
  • cGMP enters oocyte via gap junctions from cumulus cells→ inactivates phosphodiesterase
  • cAMP activates protein kinase A
  • protein kinase A phosphorylated/inactivates mitosis promoting factor (cycB/cdk1)

high cAMP in oocyte= cell cycle arrest

319

layers the follicle must breach during ovulation

from COC to outside ovary

  • stratum granulosum
  • basement membrane
  • theca interna: steroid secreting & follicular capillary network
  • theca externa
  • tunica albuginea
  • surface epithelium of ovary

320

how does FSH mediate follicle wall rupture?

increases production of plasminogen activator from mural granulosa cells→ plasmin activates collagenases

increases production of VEGF from granulosa cells

321

how does LH mediate follicle wall rupture?

increases production of matrix metalloproteins, espcially collagenases

increases production of COX2→ 100x increase in prostaglandin synthesis→ PGE2 determines site of stigma & PGF2alpha ovarian smooth muscle contraction

322

low serum levels of estradiol, LH, & FSH are associated with?

hypogonadotropic hypogonadism & hyprolactinemia (causes inhibition of GnRH)

323

high serum androgen, estradiol, & LH are associated with?

PCOS

causes no estrogen surge→ no LH surge→ no ovulation

324

most common causes of anovulation

hypogonadotropic hypogonadism

hyperprolactinemia

PCOS

premature ovarian failure

325

low serum estradiol and high serum LH & FSH is associated with?

premature ovarian failure or menopause

326

steps sperm must undergo to fertilize oocyte

  1. capacitation in uterus
  2. hyperactivation
    • allows for penetration of cumulus matrix
    • also hyaluronidase
  3. binding to zona pellucida (ZP3 on oocyte)
  4. acrosome reaction
    • acrosin allows for penetration of zona pellucida to perivitelline space
  5. cortical reaction: cortical granules released from oocyte upon membrane fusion

327

what is the fertilizable life span of sperm?

48-72 hours

328

where is sperm stored until ovulation?

fundus of uterus

329

the secondary oocyte is arrested in

metaphase II of meiosis

330

Human chorionic somatomammotropin (hCS) is produced by which cell types of the placenta?

syncytiotrophoblasts

have pituitary-like secretions of hCS, hCG, human growth hormone-variant, & adrenocorticotropic hormone (ACTH)

331

How is the fetus protected from over exposure to androgens and estrogens?

placenta & fetus lack enzymes to synthesize estrogen & prgesterone

placenta lacks 17alpha-hydroxylase & 17, 20-desmolase (together=CYP17) and 16alpha-hydroxylase

fetus lacks 3beta-hydroxysteroid dehydrogenase & aromatase

**steroids are sulfated by fetus & shunted to maternal circulation to protect fetus**

332

If fertilization does not occur, the serum concentration of which two hormones decreases abruptly?

estradiol & progesterone

333

What is the rate of increase in hCG levels during early pregnancy?

rises exponentially during first 4-7 weeks

doubles every 48-72 hours

334

What cells of the endometrium are involved w/decidualization?

fibroblast-like endometrial stromal cells

under the stimulus of progesterone

335

in a normal 28-day menstrual cycle, on what days is the endometrium most receptive to implantation?

days 19-24

end of secretory phase & before decidualization

336

WHat fetal derived cells are involved inspiral artery remodeling?

extravilous trophoblasts

differentiate from cytotrophoblasts under low O2 conditions

aggressively infiltrate decidua to remodel spiral arteries

337

What cells secrete hCG? What cells secrete hyperglycosulated hCG?

  1. syncytiotrophoblasts
  2. extravillous trophoblasts during first 2 weeks of pregnancy 
    • elevated after W20→ Downs Syndrome

 

338

at what gestational stage is hCG detectable in maternal serum and when does the concentration of maternal hCG peak?

  1. 8-10 days after fertilization
  2. peaks around 8-11 weeks

339

What is the major placental estrogen?

estriol is mostly found during pregnancy, but estradiol levels are usually still higher

340

to what receptor does hCG bind on the corpus luteum?

LH receptor

341

What androgen is the precursor for placental estradiol synthesis?

DHEA

342

What is the primary stimulus for the increased prolactin secretion during pregnancy?

estrogen

increases sensitivity of lactotrophs to TRH

decreases sensitivty of lactotrophs to dopamine→ reduces inhibition by dopamine

343

What are the primary functions of progesterone & estrogen during pregnancy?

  • progesterone
    • transforms endometrium into receptive tissue for supporting invading blastocyst
    • stimulates stromal secretion→ embryo food
    • suppresses myometrial contrractility
    • inhibits ovulation 
    • stimulates breast alveoli & inhibits lactation
  • estrogen
    • steroidogenesis
    • uterine artery blood flow
    • growth of breast, pitutary & myometrium
    • prolactin secretion, prolactin receptor expression, myometrial gap junction

344

What hormone "rescues the corpus luteum"?

hCG

345

the placenta lacks CYP17; therefore, it lacks teh ability to convert what to what?

pregnenolone sulfate to DHEAS

346

What are the primary functions of hCS during pregnancy?

binds to prolactin & growth hormone receptors

diabetogenic effects on mother

  • stimulates pancreatic insulin secretion
  • hyperinsulin response to glucose
  • increases lipolysis
  •  increases proteolysis
  • increases free fatty acids
  • minimal lactogenic fucntion
  • **not essential for fetal development**

347

Which hormone is primarily responsible for enhanced uterine blood flow during pregnancy?

estrogens

348

What is the concentration of hemoglobin in fetal blood?

15g/dL

349

What is the primary function of prolactin during pregnancy?

mammogenesis: prepare the breast for lactation

also acts w/hCS 7 hGH-V to mobilize mother's nutrients to fetus

350

at what stage of gestation does the fetus gain the most weight?

3rd trimester

351

carbohydrate intolerance that develops w/the onset of prenancy or is first recognized during pregnancy is termed what?

gestational diabetes mellitus

352

during pregnancy, how are total blood volume, RBC mass, & plasma volume altered?

all are increased

20% increase of RBC volume

45-55% increase in plasma volume

40-45% increase in total blood volume

353

what are the major changes to lung volumes & capacities that occur during pregnancy?

functional residual capacity decreases→ due to decreases in both expiratory reserve & residual volume

inspiratory capacity stays the same→ increase in tidal volume (more gaseous exchange) & decrease in inspiratory reserve

354

The PCO2 of the umbilical vein is greater than the PCO2 in the uterine vein. True or False?

False

umbilical vein (40mmHg) is oxygenated blood from mother to fetus

uterine vein is 45mmHg

355

Fetal Hb has a lower P50 than adult HbA. What is the primary consequence of this difference?

at any given PO2, HbF will bind more O2 than HbA

favors transfer of O2 from maternal to fetal blood

356

What is macrosomia?

caused by increased fetal insulin

increases fat deposition

causes birth weights over 4.5kg (9.9lbs) & altered organ development (megalies)

15-45% of diabetic pregnancies

may lead to birth injuries, shoulder dystocia, preterm birth, child obesity, T2DM in child

357

The umbilical artery has a higher oxygen saturation than the umbilical vein. True or false?

False

umbilical vein transports oxygenated blood to fetus

umbilical arteries transport deoxygenated blood from the fetus

358

total peripheral resistance falls during pregnancy, but mean arterial pressure remains relatively unchanged. How?

cardiac output increases

MAP= CO x TPR

359

how does renal blood flow change during pregnancy?

increases due to increased plasma volume & decreased renal vascular resistance

360

GFR increases during pregnancy. True or False?

increases due to increased renal blood flow 

361

Name 2 factors involved in the maintenance fo oxygen delivery to the fetus.

  • increased maternal blood supply to placenta
  • PaO2 & PaCOof maternal & fetal blood
  • higher Hb concentration in fetal blood
  • presence of HbF
  • double Bohr effect
  • double Haldane

362

According to the Pedersen hypothesis, what is the principal cause of LGA infants?

maternal hyperglycemia

363

what part of the nervous system controls emission?

point (erection)→ parasympathetic nervous system

shoot (emission)→ sympathetic nerous system

score (ejaculation)→ somatic nervous system

364

Name two neurotransmitters that cause erection.

ACh & NO

365

Name a neurotransmitters that cause emission.

Norepinephrine

366

The autonomic innervation of the penis can be remembered by the mnemonic "point, shoot, and score." which branches of the nervous system account for each stage of the male sexual response?

point (erection)→ parasympathetic

shoot (emission)→ sympathetic

score (ejaculation)→ somatic 

367

What is the primary physiological component of orgasm in men and women?

rhythmic contractions of genital muscles (?)

368

what neurotransmitters can be used to treat priaprism

epinephrine

norepinephrine

phenylephrine

369

Name two physiological changes which occur during the resolution phase in men & women.

blood pressure & respiratory rate return to normal

370

What happens during the excitement phase in men & women?

blood pressure starts to increase

respiratory rate starts to increase

pelvic congestion begins

371

in addition to the desire phase, what are the other 4 phases of teh sexual response cycle?

  1. excitement
  2. plateau
  3. orgasm
  4. resolution

372

erectile dysfunction has been recognized as a clinical marker for detection of what?

cardiovascular disease

373

Name 3 factors that increase prevalence of erectile dysfunction.

age

diabetes

obesity

heart disease

HTN

dyslipidemia

374

define retrograde ejaculation.

when ejaculate travels backward & up into the bladder

when ejaculate is detected in urine directly after ejaculation

375

define premature ejaculation.

ejaculation w/minimal sexual stimulation & before the individual wishes it to occur

29% prevalence

most common male sexual dysfunction

376

in relation to the sexual response cycle, what is the refractory period?

span of time after ejaculation characterized by inability to repeat orgasm

usually does not apply to women

377

in relation to the sexual response cycle, the refractory period is longer in women than in men. true or false.

False

women have little to no refractory period

378

how does breastfeeding affect gonadotropin release?

suppresses it

prolactin is released during breastfeeding that inhibits GnRH release→ decreasing release of Lh & FSH

379

what are the primary effects of estrogen on the breast during gestation?

ductal proliferation & branching

also stimulates synthesis & release of prolacting

high plasma estrogen & progesterone inhibit active secretory effects of prolactin on mammary alveolar epithelium

380

which hormone stimulates milk ejection?

oxytocin

381

Which hormone stimulates milk production?

prolactin

382

what does the term "functional progesterone withdrawl" mean?

in late term pregnancy, progesterone receptors decline in #

so progesterone produces less effect b/c there are less receptors

383

which hormone is primarily responsible for galactopoeisis?

prolactin

384

what is the Ferguson reflex?

neuroendocrine + feedback loop that regulates parturition

  1. mechanical stretch of cervix
  2. increases oxytocin release
  3. increases uterine contractions→ back to 1

385

Which prostaglandin stimulates smooth muscle contraction?

  • PGF2alpha→ 
    • from maternal decidua
    • myometrial FP receptors
    • promote uterine contractions
  • PGE2
    • fetoplacental origin
    • myometrial EP1 & EP3 receptors→ uterine contraction
    • myometrial EP2 & EP4→ uterine relaxation

386

which prostaglandin stimulates cervical ripening & dilation?

PGE2

fetoplacental origin

acts on EP2 & EP4 receptors

387

stimulation of which prostaglandin receptors mediate smooth muscle relaxation?

EP2 & EP4

388

what happens during the latent phase of Stage 1 of labor?

cervical effacement & dilation to 3cm

389

activation of which fetal endocrine axis appears to be a key factor in initiating phase 2 of parturition?

ferguson reflex: + feedback of oxytocin

390

uterine oxytocin receptor number reaches a maximum in phase 2 of parturition. true or false?

true

391

cervical effacement occurs during phase 1 or parturition. true or false?

true

latent stage of phase 1

392

administration of NSAIDs to a woman in labor inhibits contractions. How?

NSAIDs inhibit COX enzyme

COX enzyme synthesizes prostaglandins

prostaglandins control uterine contractions during parturition

393

target tissues for insulin

hepatocytes

skeletal muscle cells

adipocytes

394

where is GLUT-3 found?

neurons & erythrocytes

395

why is it important to tightly control blood glucose levels?

b/c neurons & erythrocytes have insulin-independent GLUT-3 transporters

these cells will die if they get too much or too little glucose

neurons would become overactive & burnout with too much glucose

396

actions of insulin

  • lowers blood glucose
  • lowers blood levels of fatty acids
  • lowers blood levels of amino acids 
  • promotes storage of
    • glucose→ glycogen
    • fatty acids→ triglycerides
    • amino acids→ proteins
  • increases expression of enzymes needed for above

397

what type of receptor does insulin bind to?

insulin receptor is a tyrosine kinase receptos

alpha-subunit binds insulin extracellularly

beta-subunit: transmembrane, ATP-binding site, & tyrosine kinase domains

homodimers via disulfide bond

398

SGLUT-1

  • found in: intestinal mucosa & kidney tubules
  • function: 
    • cotransports one molecules of glucose or galactose w/2 Na+

399

GLUT-1

  • found in: brain, erythrocytes, endothelial cells, fetal tissues
  • function: 
    • high affinity glucose transport & galactose

400

GLUT-2

  • found in: liver, pancreatic beta cells, small intestine, & kidney
  • function
    • transports glucose, galactose, & fructose
    • low affinity, high capacity
    • "glucose sensor" in pancreatic beta cells
    • co-directional: how liver releases glucose to blood

401

what are the class I glucose transporters?

GLUT-1

GLUT-2

GLUT-3

GLUT-4

402

GLUT-3

  • found in: brain, placenta, & testes
  • function:
    • high affinity glucose transport & galactose
    • primary for neurons

403

GLUT-4

  • found in: skeletal muscle, cardiac muscle, & adipocytes
  • function
    • insulin-dependent high affinity glucose transport

404

GLUT-5

  • found in: small intestines & sperm
    • lesser extent in: brain, kidney, adipocytes, & muscle
  • function
    • fructose transport
    • Class II transporter

405

what hormones can increase blood glucose?

glucagon

cortisol

epinephrine

growth hormone

thyroid hormone

406

how does amino acid levels affect glucagon release?

high amino acids increase glucagon secretion

for gluconeogenesis of amino acids

407

what substances can modulate glucagon secretion?

  • catecholamines→increases cAMP→ increase secretion
  • somatostatin→ reduces cAMP→ inhibits secretion
  • GABA→ alters cell membrane potential→ inhibits release
  • insulin→ inhibits release
  • zinc, gastrin, & CCK but not understood how

408

what is the second messenger of glucagon?

increases cAMP leves

409

actions of glucagon

  • increases gluconeogenesis
  • induces glycogenolysis
  • decreases glycogenesis
  • stimulates lipolysis
  • inhibits triglyceride synthesis
  • inhibits protein synthesis in liver
  • stimulates protein breakdown IN LIVER
  • increases ketoacid formation from free fatty acids in liver

410

function of somatostatin within the pancreas

prevent oversecretion of glucagon & insulin

prevents "burnout" of alpha & beta cells

411

what triggers hunger?

release of Ghrelin form stomach

stimulates GHRH  & neuropeptide Y in hypothalamus to stimulate appetite & eating

412

how does leptin affect eating?

secreted from adipose during absorptive state

suppresses neuropeptide Y & GHRH

stimulates hypothalamic production of somatostatin

413

how is blood glucose maintained in chronic fasting?

  • cortisol secretion begins
  • promotes protein wasting for energy source
  • muscles use fatty acids & ketone bodies as major feul
  • glucose is reserved for brain