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1
Q

the anterior pituitary originates from

A

Rathke’s pouch which is an embryonic invagination of the pharyngeal epithelium

*ectodermal tissue

2
Q

the posterior pituitary originates from

A

a neural tissue outgrowth fro the hypothalamus

*neurally derived

3
Q

characteristics of hypothalamic releasing hormones (6)

A
  1. secreted in pulsatile manner
  2. Associated w/ plasma membrane receptors and promote increase in intracellular 2nd messengers
  3. stimulate release of stored hormones of the AP
  4. stimulate synthesis of AP hormones
  5. required for maintence of target cells
  6. has autocrine effects (exhibit trophic influences over cells they regulate)
4
Q

how does the vascular system of the pituitary contribute its functions

A

it is highly vascularized (2 capillary networks) which creates a high resistance of blood flow (ie. slow), therefore even though the releasing hormones secreted by the hypothalamus are in low concentrations, they will be concentrated by the slow flow, and will strongly affect the anterior pituitary

5
Q

examples of hypothalamic releasing hormones

A
  1. TRH
  2. GnRH
  3. CRH
  4. GHRH
  5. GHIH aka Somatostatin
  6. PIF
  7. PRF (dopamine)

*all are peptides except PIP which is dopamine

6
Q

Cell types of the Anterior Pituitary and their products

A
  1. Somatotropes- GH
  2. Corticotropes- ACTH
  3. Thyrotropes- TSH
  4. Gonadotropes- LH and FSH
  5. Mammotroph/Lactotropes- PRL
7
Q

Hormones secreted by Anterior pituitary

A
  1. GH
  2. ACTH
  3. TSH
  4. PRL
  5. FSH and LH
8
Q

promotes growth of the entire body by affecting protein formation, cell multiplication and cell differentiation

A

Growth hormone

9
Q

Controls the secretion of some of the adrenocortical hormones, which affect the metabolism of glucose, proteins, and fat

A

Adrenocorticotropin (ACTH)

10
Q

Controls the rate of secretion of thyroxine T4 and triiodothyronine T3 by the thyroid gland, these hormones control rates of most intracellular chemical reactions in the body

A

TSH

11
Q

promotes mammary gland development and milk production

A

Prolactin

12
Q

promotes mammary gland development and milk production

A

FSH and LH

13
Q

Secretion from the posterior pituitary is controlled by

A

nerve signals that start in the hypothalamus

14
Q

Secretion by the anterior pituitary is controlled by

A

hormones called hypothalamic releasing and hypothalamic inhibitory hormones/factors that are secreted by the hypothalamus and are conducted to the anterior pituitary through small blood vessels called hypothalamic hypophysial portal vessels.

15
Q

LHRH is secreted in low amounts from hypothalamus –> LH or FSH from the AP are much greater.

How is such a small amount influencing the release?

A

vasculature!! capillary network–> venous structures –> capillary network –> SERIES resistance –> high R –> sluggish blood flow is why such small amounts of hormone has such a big effect !

16
Q

Regulation of hormone release from pituitary

A
  1. Ultrashort loop inhibition (autocrine inhibition)- hypothalamus releasing hormone has a neg .effect on hypothalamus
  2. Short loop inhibition- Ant. pituitary secretes a trophic hormone that has a neg. effect on hypothalamus
  3. Long loop inhibition- trophic hormone effects target cell which releases another hormone that has a neg. effect on hypothalamus and AP hormone

*hypothalamic endocrine axis!

17
Q

hormones secreted by posterior pituitary

A
  1. ADH aka vasopressin

2. oxytocin

18
Q

controls the rate of water excretion into the urine

A

ADH

19
Q

helps express milk from the glands of the breast to the nipples and helps in the delivery of the baby at the end of gestation.

A

oxytocin

20
Q

major hormones of the adrenal cortex (types of corticosteroids)

A
1. Glucocorticoids 
(cortisol, corticosterone)
2. Mineralocorticoids
(aldosterone)
3. Sex steroids (17-keto steroids)
(androgens and estrogens)
21
Q

affect the electrolytes (the minerals) of the ECF, especially sodium and potassium

A

Mineralocorticoids

22
Q

affect blood glucose concentration. They also affect protein and fat metabolism

A

Glucocorticoids

*essential for life

23
Q

what hormones are secreted from the different parts of the adrenal cortex and medullat

A

Zona Glomerulosa- Aldosterone

Zona fasciculata- glucocorticoids and sex steroids

Zona reticularis- sex steroids

medulla- epi and norepi

**All Cortex parts are stimulated by ACTH!

24
Q

describe how Cortical atrophy and hypertrophy occur

A

atrophy- caused by hypophysectomy bc it loses ACTH

Hypertrophy- caused by increase in ACTH. ( stress–> hypothalamus stimulated ==> + CRH –> + pituitary–> increase in ACTH release

*ACTH regulates adrenal cortex maintenance

25
Q

ACTH and cortisol levels increase on a diurnal rhythm, when are levels highest

A

rise at 4 am and peak around 7-8AM

*as you approach sleep/wake cycle, ACT and correspondingly cortisol increases

26
Q

all steroids are derived from

A

cholesterol

27
Q

describe the synthesis of steroids

A

ACTH binds to Gs receptor–> + PKA–> phosphrorylation–> + CEH **RLS
LDL mediates receptor mediated endocytosis –> LDLs are made of 50% cholesterol in ester form –> + CEH breaks down cholesterol esters to yield free cholesterol **RLS –> enters ER–> synthesis of steroid hormones in mito

**ACTH is literally driving the availability of free cholesterol to engage in biosynthetic activity!!!!

28
Q

describe congenital adrenal hyperplasia (CAH)

A

it is a consequence of an enzyme in the cortisol production pathway being almost non-existant. So the person lacks the enzyme machinery to engage in cortisol production. This leads to a back up of ACTH and a hyperplastic adrenal gland

29
Q

what is the dexamethasone suppression test

A

This test evaluates the integrity of the hypothalamus, pituitary, adrenal gland axis.
-Dexa is a powerful glucocorticoid given orally at night that raises glucocorticoid levels in the system. This negatively influences ACTH release and ultimately the release of cortisol

30
Q

ACTH impacts all aspects of steroid hormone synthesis. What are its impacts

A

Immediate: (via phosphorylation of CEH via PKA)–> increase cholesterol transport to mito and more bind to p450= enhanced production of steriods by a number of hydroxylases

Subsequent: increase in LDL receptors and gene transcription

Longterm: (via insluin like growth factors)–> increases the size and number of cells in the adrenal cortex

31
Q

what stimulates aldosterone secretion

A

angiotensin II

decrease in ECF volume (decrease BP)–> renin release from kidneys–> cleaves angiotensinogen from liver–> angiotensin I–> cleaved by ACE from lungs–> angiotensin II–> stimulates aldosterone release from zona glomerulosa

32
Q

how is cortisol transported to its target

A
  1. binds primarily to transcortin- 80% (has the highest affinity for cortisol)
  2. overflow cortisol binds to albumin (15%) (lower affinity for cortisol)
  3. Free cortisol in ECF that can associate with receptors
33
Q

This is our most important mineralocorticoid it is a K+ secretor Na+ keeper- lipophilic substance so it crosses membrane! Receptor is in cytoplasm or in nucleus

A

aldosterone

34
Q

aldosterone is regulated by

A

angiotensin II
Plasma Na+ reduction (causes increase in aldosterone)
Plasma K+ increase (cause increase in aldosterone)
ACTH - weak but still promotes

35
Q

our most important glucocorticoid

A

cortisol

36
Q

what are the effects of increased AA in the ECF due to increased cortisol?

A

AA undergo transamination (utilization) in the liver to produce TCA cycle intermediates (can then be used to promote gluconeogensis, glycogen synthesis, and urea cycle activity–> see an increase in BUN via deamination)

37
Q

cortisols diabetogenic results

A
  • hyperglycemic, ketogenic, lypolytic
  • increase in FFA
  • increase in plasma AA–> increase in BUN
38
Q

How does cortisol effect insulin

A
  • shifts the curve to the right

- requires more insulin to drive the same level activity bc cortisol desensitized cells to insulin

39
Q

how does cortisol affect the immune system and inflammation

A
  1. blocks NO production = decreased vasodilation
  2. blocks platelet activation factors= decreased permeability
  3. inhibits phospholipase which produces Arachidonic acid= decreased inflammation
  4. blocks interleukin production of T and B cells
  5. Blocks macrophage production of interleukins= increased fever
40
Q

what are the effects of aldosterone

A
  • increase Na+ reabsorption and passive movement of water with it (increase in [Na+] in plasma)
  • increase in K+ secretion
  • increase in ECF volume
  • increase in BP

*results in more concentrated urine

41
Q

describe the biosynthesis of catecholamines

A

-occurs in adrenal medulla

Tyrosine–>Dopa (via tyrosine hydroxylase **RLS)–> Dopamine–> norepi (via dopamine beta-hydroxylase)–> Epi (via PMNT)

Tyrosine hydroxylase and dopamine beta-hydroxylase are (+) by ACTH and sympathetic stimulation

PMNT is stimulated by cortisol

42
Q

Cushing’s can be caused by

A
  • Adenomas of the anterior pituitary that secrete large amounts of ACTH which then causes adrenal hyperplasia and excess cortisol.
  • Abnormal function of the hypothalamus that causes high levels of corticotropin releasing hormone CRH which stimulates excess ACTH
  • Ectopic secretion of ACTH by a tumor elsewhere in the body like an abdominal carcinoma
  • Adenoma of the adrenal cortex
43
Q

whats the difference between Cushing’s disease and Cushings syndrome

A

When Cushing’s syndrome is secondary to excess secretion of ACTH by the anterior pituitary this is called Cushing’s disease

44
Q

why do we see muscle wasting in Cushing’s?

A

protein is being broken down into AA so that it can be used in gluconeogenesis

45
Q

Most common adrenal disorder of infancy and childhood

A

congenital adrenal hyperplasia

46
Q

causes of congential adrenal hyperplasia

A

Secondary to defect in steroid synthesis

  • due to partial/complete lack of one or more ezymes that is responsible for making glucocortisol. Absence of the end product will not suppress the ACTH levels and this drives the hypertrophic response
47
Q

effects of deficient C21 hydroxylase in CAH

*95% of cases

A
  • Partial loss of activity = simple virilizing → don’t have complete loss, back up by-products and so shift toward the android steroid
  • Severe (salt losing)- serious deficiencies in cortisol and aldosterone → can lose 5-10% of Na loss in the DCT without aldosterone

*this enzyme is crucial for glucocorticoid and mineralicoid production

48
Q

effects of deficient C11 hydroxylase in CAH

A

serious deficiences in cortisol and aldosterone.

-Hypertension is present

49
Q

why does deficient C11 hydroxylase in CAH cause hypertension

A
  • Progressive adrenal hyperplasia due to persistent ACTH (no cortisol to inhibit it) results in an extreme overproduction of 11-deoxycorticosterone (DOC)
  • DOC is a weak mineralocorticoid, but when it reaches high enough levels it causes mineralocorticoid excess: HTN, Salt retention, and Volume expansion

*too much DOC will cause increased Na+ reabsorption in tubular cells in kidneys= increase water reabsorption= increase ECF volume=increase in BP

50
Q

why are there virilizing effects associated with C21 hydroxylase deficiency in CAH?

A

blocking C21 causes increase in 17-alpha-hydroxypregnenolone–> increase in testosterone pathway

*too much testosterone can cause increase in estradiol
but you see more increase in testosterone because most estrogen is produce in the ovaries

51
Q

what is a major source of T3

A

deiodidination of T4

52
Q

what happens with MIT and DIT get deiodinated

A

they get recycled and they contribute to the iodide pool

53
Q

what inhibits iodide transport into the thyroid follicular cell?

A

ClO4-

SCN-

54
Q

what transports T3 and T4?

A

TBG and TBPA in plasma

*TBG has a higher affinity for T3 and T4

55
Q

What coupling Rxns form T3 and T4

A

DIT + DIT (via ester linkage)= T4

DIT + MIT (via ester linkage) = T3

56
Q

what are the functional units of thyroid

A

follicles

*They are secretory cells that surround/synthesize the cells with colloid

57
Q

how is the thyroid gland able to store hormones and later use it

A
  • it stores large amounts of hormone in its colloid areas bound to thyroglobulin
  • In order to get these hormones out for use, the follicular cell must take in colloid via endocytosis and break it down into free T3 and T4.
58
Q

is T3 or T4 more potent

A

T3

*but present in much smaller quantities

59
Q

why is TSH low is hyperthyroidism?

A

T4 is increased due to hyperactive thyroid

-T4 feeds back to inihibit ant. pituitary and hypothalamus and inhibits TSH secretion

60
Q

how do you get hypertrophy of the thyroid gland?

A

overstimulation by TSH

61
Q

what are the actions of TSH

A
  1. increase metabolic activity
  2. increase cell size
  3. increase cell number
  4. increase follicular formation
  5. driving of the iodide pump
  6. increase intracellular Ca2+

*driving hyperplastic response

62
Q

describe the half lives of T3 and T4

A

T4 (Thyroxine) has a higher affinity for its carrier protein so it has a longer half life

T3 has less affinity for its carrier protein so it falls off easily and is degraded more quickly

*there is a long latent period before T4 activity begins. Note- almost all of the T4 is converted to T3 before the hormone acts on the cell. Only about 10% of hormone is still T4 at this point

63
Q

Pharmacology- these inhibit peroxidase enzyme, thus reducing thyroid hormone synthesis via inhibiting iodine formation and coupling reaction of tyrosine residues to make our T4 and T3

A

Thioamide compounds

64
Q

GH release is mediated by:

A

hormones/stress
Neurogenic
Metabolic (ex. hypoglycemia)

65
Q

what is secreted by the liver in response to GH

A

somatomedins (act as GH)

*Small proteins that have similarities to the effects of insulin on growth. So somatomedins are also called insulin like growth facts IGFs.

66
Q

what is the biggest inhibitor of GH

A

somatostatin

*released by the hypothalamus and inhibits ant. pituitary (decrease GH release)

67
Q

metabolic triggers are used to promote what hormones

A

cortisol
GH

*both hormones are diabetogenic!! (increases resistance to insulin and can cause diabetes!)

68
Q

direct effects of GH

A
  1. Adipose tissue: decrease adiposity by decrease glucose uptake and increased lipolysis
  2. Muscle: increase LBM by increased protein synthesis, increase AA uptake, and decreased glucose uptake
  3. Liver: increase RNA/protein synthesis, increase gluconeognesis, increase somatomedins
69
Q

how does GH promote increase in LBM

A

GH is enhancing the conversion of FFA to Acetyl CoA in tissues throughout the body for energy.

  • So under the influence of GH fat is used for NRG instead of carbs and proteins.
  • So GH causes an increase in lean body mass
70
Q

explain the Ketogenic effect of GH:

A

under the influence of excessive growth hormone, fat mobilization from adipose tissue sometimes becomes so great that large quantities of acetoacetic acid are formed by the liver and released into body fluids causing ketosis.

*This excessive mobilization of fat from the adipose tissue also causes fatty liver.

71
Q

GH ____ glucose up take in skeletal muscle and fat cells

A

decreases

72
Q

GH _____ glucose production by the liver and GH _____ insulin secretion.

A

increases

increases

73
Q

what factors are necessary for GH and promotion of normal growth

A

TH
glucocorticoids
insulin
gonadal steroids

**must have an intact endocrine system for GH to be released

74
Q

roles of prolactin in regards to lactation

A
  1. regulation of gene expression for milk

2. mammary gland differentiation during pregnancy

75
Q

what is unique of prolactin compared to other anterior pituitary hormones?

A

because it is the ONLY one under tonic inhibition. This term means that the hypothalamus mainly inhibits prolactin production by secreting prolactin inhibiting factor (AKA dopamine- catecholamine)

76
Q

what do somatastatins do?

A

inihibit GH and prolactin from ant. pituitary

*released from hypothalamus

77
Q

what hormones are responsible for ductal breast growth and lobulo-aveolar growth

A
  1. estrogen
  2. GH
  3. adrenal steriods
    = Ductal growth

+ progesterone + prolactin = LA growth

78
Q

how does prolactin activate its pathway

A

acts through JAK-STAT pathway–> increase in mRNA that drives milk synthesis (increase in enzyems)–> increase in lipid, protein, and lactose synthesis

79
Q

what is the main protein in cows milk and humans milk

A

Cows- Casein (Casein 80%, Whey 20%)

Humans- Whey (Casein 34%, Whey 66%, Alpha lactalbumin 3.6g/L)

80
Q

what is the role of alpha lactalbumin?

A

this protein is important for lactose synthase enzyme to make lactose from UDP-galactose

lactose synthase = alpha lactalbumin + galactosyltransferase)

81
Q

what hormones act through the JAK-STAT pathway?

A

prolactin

82
Q

what are calciums 6 roles

A
  1. Membrane potential and stabilization
  2. Cellular excitability
  3. Muscle contraction
  4. Regulation of enzymatic activity*
  5. Exocytosis* (ex. insulin release)
  6. Cellular adhesion
83
Q

sx of hypercalcemia

A
  • Neurologic signs (Fatigue, depression, mental confusion, anorexia, coma)
  • CV signs (ECG changes, arrhythmias)
  • GI/renal (BONES, STONES, and GRONE)
84
Q

describe what bones, stones, and grones means

A
bone degradation happens
kidney stones (come from 		calcium plus phosphate) and 
constipation
85
Q

sx of hypocalcemia

A
  • muscle spasms → carpopedal spasm, laryngeal spasm

- convulsions, respiratory arrest, increased intracranial pressure, irritability, depression, psychosis.

86
Q

Explain Ca2+ binding in ECF

A

Ca2+ binds to albumin
in acidic environment: albumin knocks off Ca2+ and binds H+ to decrease ECF [H+] and increase pH

in basic environment: albumin knocks off H+ and binds Ca2+ to increase ECF [H+] and decrease pH

*albumin acts as a buffer

87
Q

what is being liberated from bone via PTH

*mineralized bone contains a lot of this!

A

hydorxy-appatite= (Ca2)10(PO4)6(OH)2

88
Q

What regulates ParaThyroid Hormone (PTH) release?

A

FREE calium

  • When FREE calcium levels are too low, PTH is secreted
  • When FREE calcium levels get too high, PTH drops
89
Q

these are young cells that are responsible for making soft bone that is part of the rapidly exchangeable pool (osteoid). Lays down osteoid= non-mineralized bone = rapidly exchangeable pool of Ca and PO4.

A

Osteoblasts

90
Q

These are responsible for both bone mineralization and bone degradation. Switch Hitters.

A

osteocytes

91
Q

breaking down and eroding away of mineralization

A

Osteocytiocsteolysis

92
Q

Bone degradation/removal or resources in bone. These are the most influential to bone loss. Responsible for lysosomal activity to demineralize cortical bone

A

osteoclasts

93
Q

PTHs actions on osteoblasts/cytes/clasts

A

PTH inhibits osteoblastic activity and new bone deposition.

PTH stimulates osteolysis in osteoctyes

PTH stimulates osteoclasts to dissolve mineralized bone.

94
Q

the transfer of substances across an epithelium by passing through the intercellular space between the cells

A

paracellular

ex. Ca2+ in PCT

95
Q

a marker for osteoclast and osteocyte activity. These are driving the bone demineralization to mobilize calcium and phosphate

A

hydroxyproline

*urine hydroxyproline increases with PTH administration

96
Q

why do we see Ca2+ and (PO4)2-increase in urine with PTH administration

A

This is simply because we have mobilized stores of Ca++ and phosphate. More in the ECF means more is filtered, means more is secreted even though we are actively trying to re-absorb the calcium with PTH!!!

-increase free Ca2+ –> increased filter load of Ca2+

97
Q

what are the effects of PTH administration

A
  1. increase free Ca2+, decrease in free phosphate
  2. increase in filtered load = increase in Ca2+ and phosphate in the urine (bc of more mobilized stores of calcium and phosphate)
  3. increase in hydroxyproline (increase in bone demineralization to mobilize Ca2+ and phosphate)
  4. Decrease in TRP (tubular reabsorption of phosphate)
98
Q

Long term regulator of Ca & PO4 concentrations

A

Vit. D3

99
Q

what inhibits prostaglandins

A

aspirin

NSAIDs

100
Q

Thromboxane A2 causes

A

vasoconstriction and platelet aggregation

101
Q

Prostacyclins do what

A

counteract thromboxane A2s actions

thromboxane A2–> vasoconstriction and platelet aggregation

102
Q

essentail FA

A

linoleic acid, linolenic acid Omega 6 and 3

103
Q
  • expression is stimulated by growth factors, cytokines, and endotoxins
  • levels increase in inflammatory diseases such as arthritis
A

COX2

104
Q
  • constitutively expressed in virtually all tissues

- essential for thromboxane formation in platelets, and for maintaining integrity of the gastrointestinal epithelium

A

COX1

105
Q

competitive inhibitor of COX1 and 2

A

acetaminophen

106
Q

irreverislbe inhibitor of COX 1 and 2

*covalent modifer at active site

A

aspirin

107
Q

physiological effects of LTs (5)

A
  1. Potent chemotactic agent – LTB4
  2. Promoter of leukocyte adhesion to endothelial cells
  3. Cause vascular smooth muscle contraction – cysteinyl LTs
    (Slow reacting substances of anaphylaxis)
  4. Cause bronchiolar SM contraction
  5. Alter vascular permeability → diminish the ability of PLPA2