Physio Exam 3 Endocrine Flashcards
(475 cards)
1
Q
5 main groups of hormones
A
Derivatives of amino acids Small peptides Proteins Glycoproteins Steroids
2
Q
Ka=
A
[HR]/[H] [R]
3
Q
Kd=
A
1/KA= [H] [R]/[HR]
4
Q
what does Kd calculate?
A
receptor occupancy for any given [H]
5
Q
what activates adenylate cyclase?
A
alpha subunit bound to GTP
6
Q
what does the amount of active adenylate cyclase depend on?
A
rate of exchange of GTP for GDP and rate of hydrolysis of bound GTP
7
Q
what does cAMP do?
A
activates PKA
8
Q
what does activation of Gqa do?
A
activates PLC
9
Q
what does PLC do?
A
cleaves PIP2 into diacylglycerol and IP3
10
Q
what does IP3 do?
A
mobilizes Ca from vesicular storage sites
11
Q
what does diacylglycerol do?
A
activates PKC
12
Q
what does Gia do?
A
inhibits adenylate cyclase
activates K channels
13
Q
what does transducin/Gta do?
A
stimulates cGMP phophodiesterase in photoR
14
Q
what do serine/threonine kinases activate?
A
Smads
15
Q
what do Smads do?
A
move to the nucleus and participate with other gene regulatory proteins in influencing transcription
16
Q
what is the guanylate cyclase a receptor for?
A
ANP
17
Q
how do guanylate cyclase receptors work?
A
increase cGMP which activates PKG
18
Q
what do cytokine receptors activate?
A
JAKs
19
Q
what do JAKs do?
A
phosphorylate STATs
20
Q
what do STATs do?
A
move to nucleus and regulate transcription
21
Q
coated pits
A
where hormone-receptor complexes cluster in regions of the membrane
22
Q
coated vesicles
A
Coated pits invaginate and pinch off from the membrane
23
Q
what coats coated pits?
A
clathrin
24
Q
adaptins
A
found in the coat and recognize cytoplasmic domains of receptors to trap them in the pit
25
HRE
hormone response elements
| where steroid hormones interact with DNA
26
what kind of sequence do HREs have?
Palindromic sequences or direct repeats
27
3 structural domains of intracellular hormone receptors
c-term binding region
central DNA binding region
variable N-term
28
what is the sequence of the Central, highly conserved DNA binding domain of intracellular hormone R?
Rich in cysteine residues
29
role of Variable N-terminal domain of intracellular hormone R
Participates in recruitment of transcription factors
30
what do increases and decreases in carrier protein concentration cause?
reciprocal changes of free hormone levels
31
negative cooperativity
Increasing receptor occupancy decreases the affinity of remaining receptors for hormone
32
down regulation
Exposure of responsive cells to high concentrations of hormone can lead to a decrease the # of receptors
33
why are cells down regulated?
Protects cell from intense stimulation of chronically elevated hormone levels
34
Phosphorylation of cytoplasmic domains of the receptor decreases ___
affinity for G protein
35
what mediates uncoupling of receptors from G proteins
beta-ARK
36
beta arrestin
binds to the phosphorylated receptor and blocks the interaction with the G-protein
37
how are peptide hormones inactivated?
proteases on the cell membrane
38
how are steroid hormones inactivated?
enzymes in the liver
39
what does a hormone radioassay measure?
nanogram quantities of a hormone
40
Scatchard analysis
Determine binding constants of hormone-receptor interactions and the concentration of receptors in a preparation of cells or membrane fractions
41
what is the slope a the Scatchard analysis?
-Kd^-1
42
what is the x-intercept of the Scatchard analysis?
[Rt]- conc of total binding sites
43
sella turcica
pocket of bone at the base of the brain
44
neurohypophysis
posterior lobe of pituitary
45
what does the neurohypophysis secrete?
oxytocin
| ADH
46
adenohypophysis
anterior lobe of pituitary
47
what does the neurohypophysis develop from?
floor of brain
48
what does the adenohypophysis develop from?
roof of mouth
49
what artery supplies the posterior pituitary?
inferior hypophyseal artery
50
where are hormones from the anterior pituitary stored?
near median eminence, near cap plexus of superior hypophyseal artery
51
primary role of ADH
conserve body water and regulate the tonicity of body fluids
52
target cells of ADH
renal cells responsible for reabsorbing water
53
what stimulates ADH?
water deprivation
54
what does lack of ADH lead to?
diabetes insipidus
55
primary role of oxytocin
eject milk from lactating mammary glands
56
major stimulus of oxytocin
suckling by infant
57
effects of oxytocin
contraction of myoepithelial cells mammary gland and ejection of milk
58
stimulus of oxytocin during labor
dilation of cervix
59
effect of oxytocin during labor
positive feedback
| enhances muscle contraction
60
what is the most abundant pituitary hormone?
GH
61
what is prolactin secretion under the control of?
dopamine
62
what does prolactin do?
Induces synthesis of casein and lactalbumin in mammary glands
Stimulates breast development
63
what does excess prolactin cause?
galactorrhea
| inhibition of GnRH and menstruation
64
what does deficient prolactin cause?
failure to lactate
65
what is apart of POMC?
ACTH and β-lipotropin
66
β-lipotropin role
Induces pigmentation and affects adrenal steroid secretion
67
__ stimulates ACTH synthesis and secretion
CRH
68
half life of FSH, LH, TSH
30 min- 2 hrs
69
pituitary is under the influence of the ___
CNS
70
how does the hypothalamus influence the pituitary?
blood-borne factors called hypothalamic releasing hormones
71
where is GnRH concentrated?
medial basal hypothalamic nuclei
72
what does GnRH do?
Stimulates pituitary synthesis and secretion of LH and FSH
73
what modulates the response to GnRH?
sex steroid
74
high levels of GnRH ___
block steroidogenesis
75
what does GHRH do?
Stimulates GH synthesis and release from pituitary directly
76
what does somatostatin do?
inhibits release of GH
77
what does TRH do?
Stimulates pituitary synthesis and secretion of TSH and prolactin
78
TRH mechanism of action
Binds to specific receptors on thyrotropes and activates PLC
79
where is the highest conc of TRH?
hypothalamus
80
what does PIF do?
Tonically inhibits the secretion of prolactin
81
what does CRH do?
Stimulates pituitary ACTH synthesis and release
82
3 categories of endocrine disorders
hyposecretion
hypersecretion
hyporesponsiveness
83
primary hyposecretion
Endocrine target gland secretes too little hormone because its not functioning normally
84
secondary hyposecretion
Endocrine target gland is fine
| Tropic hormone produced by pituitary is too low
85
primary hypersecretion
Dysfunctional gland secretes too much hormone
86
secondary hypersecretion
Excessive stimulation by tropic hormone
87
hyporesponsiveness
Target cells don’t respond to the 3rd hormone
88
3 major causes of hyporesponsiveness
Lack or deficiency in receptors for the hormone
Post-receptor defect in target cell
Lack of metabolic activation of a hormone
89
how does GH act?
stimulates mitosis of many target tissues
90
what chemical messengers does GH mediate?
IGF-I, -II
91
what does plasma conc of IGF-I reflect?
availability of GH and/or the rate of growth
92
what kind of receptor is the IGF R?
tyrosine kinase
93
how does IGF-I act?
autocrine or paracrine
94
what is the main source of IGF-I?
liver
95
how is GH secreted?
episodic bursts
96
what is the primary drive for GH synthesis?
GHRH
97
what is the growth promoting hormone during fetal growth?
insulin
98
how do excess glucocorticoids effect GH secretion?
decrease
99
mid parental height
dad's height+mom's/2
| +2.5 for boys
100
excess of GH before puberty causes __
gigantism
101
excess of GH after puberty causes __
acromegaly
102
acromegaly symptoms
```
Disfiguring bone thickening
enlargement of hands and feet
protrusion of lower jaw
increased body hair
glucose intolerance
```
103
acromegaly treatment
somatostatin analogs
104
deficiency of GH symptoms
failure to grow
short stature
mild obesity
delayed puberty
105
what does the outer cortex of the adrenal gland produce?
steroid hormones
106
what does the inner medulla of the adrenal gland produce?
epi
| NE
107
layers of adrenal cortex
Zona glomerulosa
Zona fasciculata
Zona reticularis
108
Zona glomerulosa produces
aldosterone
109
Zona fasciculata produces
cortisol
110
Zona reticularis produces
cortisol
| androgens
111
main mineralocorticoid
aldosterone
112
main glucocortiocoid
cortisol
113
what does the medulla arise from embryonically?
neuroectoderm
114
what are all adrenal cortical hormones derived from?
cholesterol
115
rate limiting step of adrenal hormone synthesis
cholesterol to pregnenolone
| first step
116
StAR role
stimulates transport of cholesterol from cytosol to mitochondria
117
are glucocorticoids or aldosterone favored to bind to albumin?
glucocorticoids
118
which receptors do mineralocorticoids bind to?
type I in cytoplasm
119
which receptors do glucocorticoids bind to?
type II
120
what is the controlling factor of cortisol and androgen synthesis?
ACTH
121
Stimulation of ACTH leads to a rise in steroid hormone secretion within __ minutes
1-2
122
when does ACTH secretion peak?
early morning
123
high levels of cortisol cause
```
increased blood glucose
promotes catabolism
decreased glc use
decreased pro synth
altered fat metab
```
124
how does cortisol promote catabolism?
Facilitates breakdown of protein from muscle and CT to increase AA used in gluconeogenesis
Stimulates production of gluconeogenic enzymes in the liver
125
how does cortisol decrease glc use?
Inhibits glucose transport into cells except for brain
126
how does cortisol alter fat metabolism?
Increases rates of peripheral fat breakdown → liberate FA and glycerol for gluconeogenesis
Increases central fat deposition
127
CNS effects of cortisol
Feedback inhibition of CRH and ACTH
Affects perception
Initial euphoria followed by depression
128
CVS effects of cortisol
Maintains sensitivity to epinephrine and norepinephrine in vasculature
129
developmental effects of cortisol
Permissive role in maturation of fetal organ systems, intestinal enzymes, surfactant
130
renal effects of cortisol
Cortisol exerts feedback inhibition on secretion of CRH and ADH
131
bone effects of cortisol
Promotes bone breakdown by increasing osteoclast activity
132
immune function of cortisol
suppresses body's inflammatory response
133
what does prolonged administration of glucocorticoids cause?
feedback inhibition of ACTH production, atrophy of adrenal cells, reduced ability to produce cortisol
134
how is cortisol eliminated by the body?
Filtered by glomerulus and appears in the urine
| Enzymatically reduced in the liver
135
when are adrenal androgens critical?
fetal development
136
primary function of aldosterone
increase sodium reabsorption in the distal nephron
137
what is the production of aldosterone under control of?
AII
plasma K
ACTH
138
what is the consequence of increased aldosterone during pregnancy?
expanded ECF
139
what are the cells of the adrenal medulla?
chromaffin
140
ratio of catecholamines in chromaffin cells
5 epi:1 NE
| 1ATP:4 catecholamines
141
what are catecholamines made from?
tyrosine
142
what enzyme catalyzes the conversion from epi to NE?
PMNT
143
what stimulates release of chromaffin granules?
sympathetic cholinergic stimulation
144
half life of catecholamines
10-15 seconds
145
B cell of pancreas role
produces insulin
146
A cell of pancreas role
releases glucagon
147
D cell of pancreas role
releases somatostatin
148
PP cell of pancreas role
releases pancreatic polypeptide
149
pancreatic polypeptide role
Inhibition of gallbladder contraction
| pancreatic enzyme secretion
150
how does blood flow in the pancreatic islet?
center outwards
151
what do Sulfonylureas do?
stimulate insulin secretion
152
how does glucose enter the beta cell?
GLUT2
153
how does increased glc cause insulin release from the beta cell?
Increased glucose metabolism → increased ATP/ADP ratio → close ATP sensitive membrane K channel → membrane depolarization → opens voltage sensitive Ca channel → Ca enters cell → exocytosis of secretory granules
154
2 functions of insulin R
Recognize and bind insulin with high affinity and specificity
Generate the signals that modulate insulin’s effector function
155
insulin R structure
glycoprotein with 2 alpha and 2 beta subunits linked by disulfide bridges
156
alpha subunit of insulin R
externally oriented and contains the insulin binding site
157
beta subunit of insulin R
transmembrane protein that plays a role in signal transduction
158
how does insulin regulate glc homeostasis?
controlling hepatic glucose production and utilization of glucose by muscle and adipose tissue
159
what tissues have GLUT4?
muscle
| adipose
160
how does insulin increase K into cells?
increase of activity of Na-K ATPase
161
major stimuli for glucagon secretion
falling blood glucose
elevated AA in plasma
sympathetic stimulation
162
what inhibits glucagon secretion?
elevated blood glucose
somatostatin
insulin
163
where does glucagon have most of its effects
liver
164
how does glucagon act?
via receptors with Gs proteins → increases cAMP
165
actions of glucagon
Promotes glycogenolysis and gluconeogenesis → increase glucose release
Increases beta oxidation
166
what drives satiation?
release of appetite-inhibitory peptides from GI tract
167
how do satiety peptides slow the return of hunger?
decrease rate of gastric emptying
168
incretin
peptide hormone that stimulates insulin secretion and improves glucose tolerance during a meal
169
what is the only peptide that increases appetite?
ghrelin
170
where does ghrelin bind?
appetite stimulatory neurons in the hypothalamus
171
actions of ghrelin
Increases food intake
body weight
Decreases fat breakdown
172
adiposity hormone
Basal hormone levels parallel the amount of adipose tissue
173
where does leptin bind
receptors on hypothalamic neurons
174
which hormone inhibits appetite
leptin
175
__ levels fall with long term exercise programs
leptin
176
orexigenic
appetite stimulating
177
anorexigenic
appetite inhibiting
178
2 peptides in orexigenic pathway
NPY
| AgRP
179
what inhibits orexigenic ARC neurons?
leptin
180
2 peptides in anorexigenic pathway
CART
| POMC
181
what does AgRP inhibit?
melanocortin R in anorexigenic circuit
182
1,25[OH]2D3 main effects
Increases calcium absorption from intestine
183
PTH main effects
Mobilizes calcium from bone
| Increases phosphate excretion
184
calcitonin main effects
Ca lowering
| inhibits bone resorption
185
consequence of low Ca conc
increases excitability of nerve and muscle cells → hypocalcemic tetany
186
consequence of high Ca conc
cardiac arrhythmia
| depresses neuromuscular activity
187
how much Ca is in the rapidly exchangeable pool?
500mM
188
what 2 homeostatic systems affect the Ca in bone?
plasma Ca
| bone remodeling
189
what regulates Ca in the GI tract?
1,25[OH]2D3 through negative feedback mechanisms
190
osteoblasts
bone forming cells
Secrete collagen and form a calcified matrix
Derived from fibroblast precursor cells
191
osteocytes
differentiated osteoblasts surrounded by bone matrix
| Send processes throughout the bone
192
osteoclasts
multinuclear cells that digest and resorb bone
Derived from monocytic precursors
Secrete acids and proteases
193
how is vitamin D3 produced?
action of UV light on 7-dehydrocholesterol in the skin
194
how is vitamin D3 transported?
through vitamin D binding protein in the plasma
195
what happens to vitamin D3 in the liver?
hydroxylated at the 25 position
196
where does vitamin D3 become bio active?
kidney
| hydroxylated at 1 position
197
what stimulates kidney production of 1,25[OH]2D3
PTH
hypocalcemia
hypophosphatemia
198
how does PTH increase production of 1,25[OH]2D3 in kidney
decreases intracellular phosphorus concentration in the kidney by enhancing phosphate diuresis
199
main action of 1,25[OH]2D3
provide Ca and phosphate to ECF for bone mineralization
200
deficiency of 1,25[OH]2D3 in children causes?
rickets
201
deficiency of 1,25[OH]2D3 in adults causes?
osteomalacia
202
VDR
Transcription factor which regulates gene expression
| Produces mRNAs that code for various Ca-binding proteins and Ca and phosphate transporters
203
1,25[OH]2D3 inhibits proliferation of cells with __
VDR
204
main action of 1,25[OH]2D3 in GI
increase Ca pumping out of basolateral membranes
205
how does 1,25[OH]2D3 increase Ca pumping out of basolateral membranes
Promotes phosphate and Ca uptake
Ca entry is enhanced by increases in epithelial Ca channels and intracellular Ca binding protein
Upregulates Ca/Na exchange mechanisms
206
main action of 1,25[OH]2D3 in bones
Mobilizes Ca and phosphate by increasing pumping through osteoblasts
207
main action of 1,25[OH]2D3 in kidney
Facilitates Ca reabsorption in proximal and distal nephron
208
main action of 1,25[OH]2D3 in distal tubule
Induces formation of ECaC and calbindin → enhances Ca uptake
209
main action of 1,25[OH]2D3 in proximal tubule
Increases expression of Na-dependent phosphate transporter → enhances phosphate reuptake
210
how is 1,25[OH]2D3 regulated
Negative feedback from plasma Ca and phosphate
Negative feedback from 1,25[OH]2D3 overproduction on 1-alpha hydroxylase
Positive feedback from 1,25[OH]2D3 stimulation of renal 24-hydroxylase and production of 24,25[OH]2D3 → degradation
211
half life of PTH
20 min
212
where is the Ca sensor?
parathyroid gland
213
5 main actions of PTH
Increases bone resorption and mobilizes
Decreases plasma phosphate
Increases Ca reabsorption in distal tubules
Increases formation of 1,25[OH]2D3 → increases Ca absorption in intestines
Increases formation of osteoclasts and osteoblasts
214
how does PTH increase bone resorption
Increases permeability of Ca in bone fluid of osteoclasts and osteoblasts
215
how does PTH decrease plasma phosphate
Increases urine phosphate excretion
216
what expresses RANKL
osteoblasts
217
what expresses RANK
Precursor monocytic osteoblasts
218
what is OPG?
decoy that blocks RANKL and RANK interactions
219
what enhances OPG production
estrogens
220
what inhibits OPG
cortisol
221
short term effect of PTH
increase osteoblastic activity
222
prolonged effect of PTH
apoptosis of osteoblasts
223
what does pulsatile PTH cause?
bone formation
| avoids apoptosis effect
224
actions of PTH in the kidney
PTH increases Ca reabsorption in the distal nephron
| Inhibits reabsorption of phosphate in the proximal tubule
225
how does PTH work in the kidney
PTH activates AC in the basolateral membrane → cAMP
| Inactivates Na/phosphate cotransporter in the luminal membrane
226
high amounts of FGF-23 cause
decrease number of Na/phosphate cotransporters → reduces phosphate reabsorption
Decreases conversion of 25OHD3 to 1,25[OH]2D3
227
what produces FGF-23
osteoblasts
228
what causes production of FGF-23?
elevated 1,25[OH]2D3
229
Mg deficiency causes?
decreased skeletal response to PTH
| decrease release of Ca into blood
230
high levels of Mg cause?
inhibit PTH production
231
Mg deficiency CVS effects
impaired Na/K ATPase → increased movement of K to ECF → alters intracellular/extracellular ratio
232
high Ca effect on PT gland
inhibited PTH secretion → Ca deposited in bone
233
low Ca effect on PT gland
increased PTH secretion → Ca mobilized from bones
234
1,25[OH]2D3 effect on PT gland
decreasing production of pre-pro-PTH
235
Trousseau’s sign
muscle spasm that causes flexion of wrist and thumb with finger extension
236
PT gland tumor effects
```
Hypercalcemia → cardiac arrhythmia
Hypophosphatemia
Demineralization of bones
Hypercalciuria
Ca stones
```
237
PTH-related peptide actions
same as PTH
| leads to decreased PTH levels and hypercalcemia
238
what secretes calcitonin
C cells of thyroid
239
when is calcitonin secreted?
when thyroid gland is perfused with high Ca
240
half life of calcitonin
10 minutes
241
actions of calcitonin
Decreases plasma Ca and phosphate by decreasing bone resorption
Increases Ca excretion in urine
242
how does calcitonin decrease plasma Ca
Acts via receptors on osteoclasts
Inhibits resorption
Decreases Ca permeability in osteoclasts and osteoblasts
243
how do excessive levels of glucocorticoids effect Ca
Decrease absorption of Ca by intestine
Increase excretion by kidney
Bone resorption
negative balance
244
GH effects on Ca
increases intestinal absorption
245
T3 and T4 effects on Ca
Increase Ca by increasing bone resorption
246
GnRH
gonadotropin releasing hormone
| AK luteinizing releasing hormone
247
1/2 life of GnRH
4 min
248
how is GnRH released?
pulsatile
249
what does GnRH act on?
gonadotropes of anterior pituitary
250
what does GnRH induce?
FSH and LH via phospholipase C signaling
251
consequences of constant GnRH levels
low FSH and LH due to down regulation of GnRH receptors
252
1/2 life of LH
20-30 min
253
what does LH act on?
interstitial steroidogenic cells → Leydig cells of the tesis and theca cells of the ovaries
254
FSH 1/2 life
2-3 hours
255
what does FSH act on?
follicular cells → sertoli cells of the testis and granulosa cells of the ovary
256
LH and FSH have a common alpha subunit with __ and __
TSH
| hCG
257
how do LH and FSH act on cells?
AC/cAMP/PKA
258
what produces T?
leydig cells of testis
259
T affect on Hypothalamic-Pituitary-Gonadal Axis
Inhibits LH release by anterior pituitary and decreases GnRH release by the hypothalamus
260
how is T converted to DHT?
5alpha reductase 1 and 2 in target tissues
261
E1
estrone
262
E2
estradiol
263
E3
estriol
264
which estrogen is a fetal adrenal and liver placental product?
E3
265
what cells make androgen precursors female
theca cells
266
where and how are androgens converted in females
granulosa cells
| FSH induced aromatase
267
Moderate, steady levels of estrogen inhibit ____ early in the menstrual cycle
LH release
268
Rising levels of estrogen increase LH release before ___
ovulation
269
what produces progesterone
corpus luteum after ovulation
270
progesterone inhibits?
GnRH release
271
__% of sex steroids are bound in plasma
98
272
⅔ of T is carried by ____
gonadal steroid binding globulin
273
1/2 of T is carried by ___
albumin
274
inhibins
Glycoproteins with and alpha chain and 1 of 2 beta chains
275
what produces inhibins?
FSH stimulated sertoli or granulosa cells
276
where do inihbins act and what is their action?
Acts on the anterior pituitary to decrease FSH release
277
what kind of system are inhibins?
negative feedback
278
inhibin B
produced during follicular phase and in males
279
inhibin A
produced during luteal phase
280
what determined gonadal sex?
internal genitalia
281
what induces testis development?
SRY
282
turner syndrome karyotype
XO
283
turner syndrome symptoms
```
Streak gonad
Amenorrhea
Short stature
Webbed neck
Lacking secondary sex characteristics
1/5000 births
```
284
Jacobs syndrome karyotype
XYY
285
jacobs syndrome symptoms
Seemingly normal male
Excess acne
Taller than normal
More aggressive
286
Klinefelter's syndrome karyotype
XXY
287
Klinefelter's syndrome symptoms
```
Male genitalia
Increased FSH, LH, E2
Decreased T
Sterility
Feminization
Retardation
Common
```
288
what syndrome is an example of hypergonadotropic hypogonadism
Klinefelter's syndrome
289
what defines phenotypic sex?
genital ducts and external genitalia and by secondary sex characteristics
290
what produces mullerian inhibiting hormone
sertoli cells
291
what supports differentiation of wolffian ducts?
T produced by leydig cells
292
when does the prostate, urethra, penis, and scrotum develop?
after T is converted to DHT
293
why do mullerian ducts form in females?
lack of MIH and T
294
what supports fetal steroidogenesis?
hCG
295
when do T levels reach their max?
mid-late 20s
296
thelarche
breast development
297
pubarche
pubic hair development
298
menarche
1st period
299
why are postmenopausal LH and FSH high?
low E
| lack of inhibin
300
Long bone growth augmented by ___
sex steroids
301
adrenarche
increased secretion of androgens without changes in cortisol or ACTH levels
302
testicular feminization
XY genotype with female external genitalia
303
cause of testicular feminization
no functional androgen R
304
5 alpha reductase deficiency syndrome
XY genotype
Begins life with female phenotype, later reverts to male phenotype
testes and internal male ducts but no prostate, penis, or scrotum because there is no DHT
305
5 alpha reductase deficiency syndrome cause
one of the 2 5 alpha reductase genes in nonfunctional
306
female CAH symptoms
Masculinization
Enlargement of clitoris and fusion of labia
Increased muscular development and facial hair → hirsutism
Irregular menses
307
male CAH symptoms
Precocious puberty or supermasculinization
308
CAH cause
hypersecretion of androgens due to defect in steroid biosynthesis
309
Spermatogonia
germ cells, sperm producing stem cell line
310
leydig cells
interstitial cells, stimulated by LH, synthesize and secrete T
311
sertoli cells
follicular cells, stimulated by FSH, nurse developing sperm
312
what connects sertoli cells?
tight junctions that form a blood testis barrier
313
Seminiferous tubules
sperm production
314
rete testis
collects sperm from multiple seminiferous tubules
315
Efferent ductules
conducts sperm to epididymis
316
Epididymis
passage where sperm undergo maturation
317
Vas Deferens
exit for sperm to seminal vesicles
318
seminal vesicle
drains into vas deferens above the prostate
| Form ejaculatory duct
319
what does the seminal vesicle produce?
fructose
| prostaglandins
320
Prostate gland
joins ejaculatory duct with urethra
321
what does the prostate produce?
buffered secretions to aid sperm in motility and fertilization
322
Bulbourethral (Cowper’s) gland
drains into urethra
| Produces lubricating mucus
323
Urethra
common urogenital passage through penis
324
Scrotum
external pouch that suspends testes away from body
325
Cryptorchidism
testes remain in abdomen
| Infertile, but virile
326
sperm pathway
```
Seminiferous tubules
rete testis
efferent ductules
epididymis
vas deferens
ejaculatory ducts
prostate
urethra
```
327
spermatogenesis
```
Spermatogonium
continual mitosis
primary spermatocyte (2n/2DNA)
1st mitotic division
2 secondary spermatocytes (1n/2DNA)
2nd mitotic division
4 spermatids (1n/1DNA)
loss of cytoplasm
4 sperm
```
328
how long to form primary spermatocyte?
2 months
329
how long to pass through epididymis?
12 days for full maturation
330
fetal T effects
induces Wolffian derived duct system directly
| Induces prostate, urethra, penis, scrotum through DHT
331
puberty T effects
induces facial, pubic, axillary hair, sebaceous glands, sperm production, larynx development, fat and muscle distribution, promotion of bone growth and cessation of bone growth
332
adult T effects
sex drive, muscle growth and maintenance, erythropoiesis, male pattern baldness, cholesterol
333
Oligospermia
<20 million sperm/ml
334
Oligospermia causes
decreased GnRH, poor nutrition, environmental factors
335
viagra effects
inhibits phosphodiesterase-5 → hydrolyzes the cGMP involved in Ca channel closure
336
Oogonia
germ cells
337
theca cells
interstitial cells
338
theca cells are stimulated by ___ to produce androstenedione
LH
339
granulosa cells
follicular cells
340
female counterpart of leydig cells
theca cells
341
female counterpart of sertoli cells
granulosa cells
342
granulosa cells are stimulated by __ to produce aromatase
FSH
343
role of aromatase in females
Converts androstenedione → estrogen
344
Fimbriae
ciliated, finger-like structures on the ampulla of the oviduct
345
Oviduct
uterine tube/Fallopian tube
346
Fimbriae role
Receives ovum from ovary
347
oviduct role
Transports ovum from ovary to the uterus
| Provides appropriate environment for fertilization
348
oogenesis
Oogonia → continual mitosis until birth → fixed # of primary oocytes (2n/2DNA)
Reduced 10x through atresia by puberty
Primary oocyte → 1st mitotic division → 2ndary oocyte (1n/2DNA) plus polar body
→ 2nd mitotic division → egg (1n/1DNA) plus polar body
349
early follicular stage hormones
LH and FSH rise as inhibitors fall
350
what hormone stage does menstruation take place in?
early follicular
351
what stimulates new cohorts of follicles?
rising FSH
352
what do proliferating granulosa cells secrete during the early follicular phase?
inhibin B
353
mid follicular stage hormones
rising inhibin B suppresses FSH release
354
what does the FSH decrease cause in the mid follicular stage?
stimulates dominant follicle, atresia of others
355
why do E levels increase in the mid follicular stage?
LH-stimulated theca cell production of androgens and conversion by aromatase into estrogen in granulosa cells
356
what does E cause in the mid follicular stage?
growth of granulosa and theca cells through paracrine signalling
357
late follicular stage
estrogen induced growth of follicle → rising estrogen levels → follicular growth
358
what does the increased E cause in the late follicular stage?
anterior pituitary increased sensitivity to GnRH by increased GnRH R on gonadotropes
Positive feedback
increased LH R on theca cells
359
what happens to LH during the late follicular stage?
increases
360
why does ovulation occur?
due to increase in LH action on granulosa cells
| Releases lytic enzymes and prostaglandins to expel oocyte
361
early luteal stage
remaining luteal cells produce less estrogen and inhibin B and more progesterone and inhibin A
362
mid luteal stage
corpus luteum grows
| Increase progesterone, estrogen, inhibin A
363
what does Increase progesterone, estrogen, inhibin A cause in the mid luteal phase?
Inhibits GnRH and LH
| Inhibin A inhibits FSH
364
what is produced if implantation occurs?
hCG
365
late luteal phase
corpus luteum degenerates
| Progesterone, estrogen, inhibin A decrease
366
what happens at the end of the hormonal cycle?
FSH and LH rise and stimulate a new cohort
367
menstrual phase days ___
1-5
368
events during menstrual phase
Initiation to completion of bleeding
| endometrium sloughs off
369
Proliferative phase → days ___
5-14
370
proliferative phase events
Under the influence of estrogen, endometrium regenerates, thickens, and forms glandular structures
Progesterone R appear on endometrial cells due to estrogen
Myometrium thickens and acquires progesterone R
371
Secretory phase → days __
14-28
372
secretory phase events
Increasing progesterone → mucus and fluid secretion, glycogen synthesis, vascularization
Inhibits myometrial contraction
Preparing for implantation
373
effects of estrogen and progesterone at the end of the menstrual cycle
Decrease estrogen and progesterone → deprive endometrium of support → constriction of blood vessels, reduced blood flow, prostaglandin secretion, death of tissue
374
what do estrogens stimulate
```
growth and maintenance of the reproductive tract
female body configuration
bone growth
epiphyseal plate closure
pubic hair growth
cervical mucus secretion
breast development
prolactin secretion
myometrial contraction
```
375
what do estrogens inhibit
GnRH release
milk producing effects of prolactin
atherosclerosis
376
what does progesterone stimulate
breast glandular growth
uterine secretion
cervical mucus secretion
increased body temp
377
what does progesterone inhibit
GnRH release
myometrial contractions
milk producing effects of prolactin
378
why is there an increase in temp after ovulation that persists thru the luteal phase?
Thermogenic effect of progesterone
379
Clomiphene
E2 agonist
| Increases GnRH → increased FSH
380
Phased protocols for assisted ovulation
Administration of FSH while blocking normal cycle with GnRH antagonist
Terminate with a pulse of hCG to trigger ovulation
381
how do progestin only BC work?
decrease LH, FSH, E2
| Suppresses ovulation and produces thick cervical mucus and a thin atrophic endometrium
382
Capacitation
epididymis derived proteins are stripped off sperm
Transmembrane proteins rearranged
Metabolism and motility increase
383
Hyperactivation
R-mediated Ca influx converts slow wave-like beating to rapid whip-like beating
384
what triggeres hyperactivation of sperm
paracrine signal from egg
385
Acrosome reaction
sperm head binding to zona pellucida → exocytosis of a trypsin-like proteolytic enzyme (acrosin) from the acrosome
386
what produces hCG
trophoblasts after invasion into endometrium
387
role of hCG
Maintains corpus luteum for 2 months
Stimulates P and E production
Prevents further ovulation
388
functional progesterone withdrawal
Efficacy of inhibition decreases as childbirth approaches
| Ratio and distribution of P R isoforms change
389
RU486
Competitive inhibitor of progesterone
| Causes endometrial degradation and myometrial contraction
390
what are the cooperative products of fetal adrenal synthesis of DHEAS from placental pregnenolone
Estradiol/estriol
391
Placental Lactogen role
Facilitates breast development
Maintains positive protein balance
Mobilizes fat for energy
Promotes high glucose levels required for nourishing fetus
392
how are uterine muscles coupled?
E-induced gap junctions
393
what stimulates uterine muscles?
stretch
394
what induces oxytocin R
estrogen
395
what cooperatively stimulates breast development
E and P, placental lactogen, and prolactin
396
what makes prolactin
lactotrophs in anterior pituitary
397
half life prolactin
20 min
398
prolactin functions
Mammogenesis
Lactogenesis
Galactopoiesis
399
Mammogenesis
growth and development of mammary gland
400
Lactogenesis
initiation of lactation
401
Galactopoiesis
maintenance of milk production
402
what inhibits prolactin release
dopamine
403
what stimulates prolactin
estrogen
404
milk ejection reflex
Suckling → neural input to the hypothalamus → inhibits dopamine release, stimulates PRF release
405
how to stimulate milk synthesis
Decrease dopamine → anterior pituitary releases prolactin → stimulates milk synthesis
406
what does oxytocin stiulate
myoepithelial cells of the breast to contract
407
most basic role of thyroid hormone
gain control → amplification or diminution of physio processes
408
what is the chemical structure of thyroid hormone based on?
thyronine
409
thyroxine
T4
| fully iodinated thyronine
410
most physio active form of thyroid hormone
T3
| 3’,3,5-triiodothyronine
411
Thyroid hormonogenesis
Thyroid hormonogenesis → iodination and coupling of tyrosine rings to make thyronine
412
what kind of NZs are important for thyroid hormone metab
selenium containing
413
TRH
Thyrotropin releasing hormone
| stimulates TSH in anterior pituitary
414
what syntesizes and secretes TRH
cells in the median eminence and arcuate nucleus
415
what stimulates TRH
neurogenic input
Alpha-adrenergic catecholamines
vasopressin
416
most important regulator of TRH
long loop neg feedback from plasma T3 and T4
417
how is TRH inactivated?
TRH-degrading ectoenzyme
418
what synthesizes and secrete TSH?
Thyrotropes in the anterior pituitary
419
physio role of TSH
stimulate thyroid follicular cells
420
what controls synthesis of TSH
plasma levels of free thyroid hormones
421
where does most T3 in the thyrotrope come from?
intra-pituitary conversion of T4 → T3
| Acheived by deiodinases
422
Binding of T3 to nuclear R ___
inhibits production of TSH
423
TRH ___ negative control of TSH
antagonizes
| promotes synthesis
424
what kind of secretion does TSH have?
pulsatile with a circadian rhythm
| Levels are higher at night
425
what inhibits TSH secretion?
dopamine
| somatostain
426
__ inhibits the thyroid axis
glucocorticoids
427
how do glucocorticoids inhibit the thyroid?
Inhibit hypothalamic expression and synthesis of TRH
Decreased responsiveness of thyrotrope to TRH
Decreases plasma T3 levels by inhibiting deiodinase activity in the pituitary and peripheral tissues
428
how does I- get into the follicle cell?
MIS
429
where is TG synthesized and glycosylated?
within follicular cells
430
where do thyroid hormonogenic processes take place?
lumen
431
what catalyzes thyroid hormonogenic processes take place?
thyroid peroxidase (TPO)
432
where do Chemical reactions catalyzed by TPO take place?
outer apical membrane surface
433
what mediates TPO recations?
hydrogen peroxide generated by NADPH oxidase
434
pendrin
Cl-I transport protein on the apical membrane
435
organification
TPO Covalently attaches iodine atoms to aromatic tyrosine rings in thyroglobulin
436
how to get precursor forms of thyroid hormones
Combines 2 iodinated rings while they are still attached to thyroglobulin
437
how much organified TG is stored in colloid?
2-3 months
438
how does TG turn into T3 and T4?
Thyroglobulin undergoes proteolysis → T3 and T4, constituent AA of thyroglobulin into cytosol
439
how do. T3 and T4 enter the bloodstream
specific transporters at the basolateral membrane
440
what is an important regulator of TH production
iodine
441
Rate limiting step of TH synthesis
iodide transport from bloodstream into follicular cell
442
perchlorate
Competitive inhibitors of NIS
443
Wolff-Chaikoff effect
autoregulatory mechanism that protects against acute iodine excess
444
how long does the Wolff-Chaikoff effect last
26-60 hours
445
how does Wolff-Chaikoff effect end?
escape- Effect diminishes as the gland escapes from inhibition by adapting to higher iodine levels and resumes normal hormone synthesis
446
Majority of circulating T4 and T3 are bound to ___
plasma proteins
Thyroxine binding globulin (TBG)
Albumin
Transthyretin
447
Physiological thyroid states correlates with ___
free hormone levels
448
All of the T4 in the bloodstream comes from ____
direct secretion from the thyroid gland
449
20% of the T3 in the bloodstream comes ___
directly from the thyroid
450
80% of the T3 in the bloodstream comes ___
from peripheral conversion of T4 → T3 by intracellular deiodinase
451
T3 or T4 faster metab rate?
T3
452
how do Th exert effects?
binding to non-histone protein nuclear receptors in conjunction with thyroid hormone response elements (TREs)
Affects the types and rates of translation of various RNAs in cells for enzymes and other cellular products
453
what tissues have a lot o TH R?
myocardial
| liver
454
sympathetic adrenergic TH effects
increase beta R activity
| increase beta R in heart, liver, muscle, adipocytes
455
energy expenditure TH effects
↑Na+/K+-ATPase expression
↑thermogenesis, heat dissipation
↑ adaptation to cold climate
456
oxygen consumption TH effects
increase number mitochondria in most tissues
457
heart TH effects
↑ contractility (positive inotropic effect)
↑ sarcoplasmic Ca2+-ATPase expression
↑ activity and number of β-adrenergic receptors
458
skeletal muscle Th effects
↑ protein catabolism and glycogenolysis
| Muscle fiber type switch from slow to fast
459
GI tract TH effects
maintains normal gut motility
| ↑ glucose absorption
460
cholesterol TH effects
↑ cholesterol synthesis
| ↑ LDL clearance (by ↑ hepatic LDL receptors)
461
skeletal TH effects
promotes bone maturation, advances bone age
promotes bone growth (permissive for IGF-1 and
maintains normal GH gene expression)
↑ bone turnover in adults
462
plasma hormones TH effects
maintains normal half-lives of hormones and drugs
463
NS TH effects
maintenance of normal mental/emotional function and
| normal reflexes, including respiration
464
when does thyroid gland form in fetus
1st trimester
465
why does TBG production increase in pregnancy?
Allows total thyroid hormone pool to increase during gestation without increasing free hormone levels
466
hyperthyroidism symptoms
```
Basal metabolic rate is increased
Voracious appetite
Weight loss
Hyperdefecation
Nervousness
Tremors
Tachycardia
Larger pulse pressure
Increased SV and CO
Lower systemic vascular resistance
Shortened circulatory times
Thin, smooth skin
Increased heat production and intolerance
```
467
hyperthyroidism treatment
Aimed at decreasing overproduction with drugs that inhibit synthesis or inhibiting peripheral effects
Surgery or radioactive iodine therapy → destroy gland to create a hypothyroid state that can be treated
468
hypothyroidism symptoms
```
Slowing of metabolic rate
Can lead to high cholesterol
Cold intolerance
Lethargy
Fatigue
Dementia
Thick, dry skin
Constipation
Bradycardia
```
469
hypothyroidism treatment
Hormone replacement therapy
| T4 has a longer half life, used more than T3
470
what life threatening emergency can hypothyroidism cause?
myxedema coma
471
what life threatening emergency can hyperthyroidism cause?
thyroid storm
472
graves disease cause
Caused by autoantibodies against TSH R
| Mimics action of TSH
473
hashimoto's cause
Non stimulating autoantibodies against the thyroid
| Eventually destroys gland
474
what causes a goiter in hashimotos?
inflammation and lymphocytic infiltration
475
thyroiditis
Inflammation of thyroid gland
| Hyperthyroidism followed by hypothyroidism then euthyroidism
