Adrenal Cortex 1-3

Front 1

Adrenal medulla and cortex embryonic origin

Back 1

neuroectodermal; mesodermal

Front 2

What does adrenal medulla secrete?

Back 2

Catecholamines epinephrine and norepinephrine

Front 3

What does the adrenal cortex secrete?

Back 3

Three classes of hormones: glucocorticoids, mineralocorticoids, androgens

Front 4

What are the zones of the adrenal cortex and what do they secrete?

Back 4

From outermost to inner:

1) Zona glomerulosa: Mineralocorticoids

2) Zona fasciculata: Glucocorticoids, androgens

3) Zona reticularis: Glucocorticoids, androgens

Front 5

What are the cells of the adrenal medulla?

Back 5

Modified postganglionic sympathetic neurons (chromaffin cells because of what stains them)

Front 6

What is the function of glucocorticoids? What is the most well known glucocorticoid?

Back 6

Function is to elevate blood glucose. Cortisol

Front 7

What is the function of mineralocorticoids and what is the most well known one?

Back 7

To conserve sodium; aldosterone

Front 8

What controls cortisol secretion?

Back 8

Pituitary-adrenocortical system.

Hypothalamus (via corticotropin releasing hormone, CRH) ----> ant pituitary (via adrenocortocitropic hormone, ACTH) ----> The adrenal cortex (z. fasciculatis and reticularis) ---> release cortisol

Front 9

What controls aldosterone secretion?

Back 9

RAA system. (zona glomerulosa)

Front 10

What are the two prominent plasma binding proteins?

Back 10

Albumin (low affinity, high capacity) and Corticosteroid binding globulin (CBG) (high affinity, limited capacity/saturable)

Front 11

What are the functions of corticosteroid binding plasma proteins?

Back 11

1) Increase solubility of steroid in plasma

2) Controls distribution of steroids to tissues

Front 12

What does liver conjugate corticosteroids with?

Back 12

Glucoronide and sulfate

Front 13

What is the feedback of cortisol on ACTH?

Back 13

Negative feedback.

ACTH hypersecretion occurs after direct lowering of cortisol; ACTH hyposecretion (and often times, adrenal atrophy) occurs after exogenous glucocorticoid treatment or primary hypercortisolism (adrenal tumor)

Front 14

If the adrenal cortex were totally removed, what would happen to ACTH?

Back 14

It would greatly increase

Front 15

How do alterations in Corticosteroid binding globulin (CBG) levels influence level of function of the pituitary-adrenocortical system?

Back 15

<b>Unbound cortisol is the feedback signal.</b>

Elevated CBG stimulates pituitary-adrenal functions. Decreased CBG is inhibitory (decreased bioavailability)

Front 16

What %age of cortisol is normally bound to proteins?

Back 16

90-95%

Front 17

What effects would removing liver/decreasing function of liver have on adrenal cortex?

Back 17

Would cause atrophy.

This is because it would slow the clearance of cortisol, a higher [cortisol] would be present in blood, and ACTH secretion would decrease.

Front 18

What stimulates cortisol clearance? Inhibits?

Back 18

thyroxine, food intake, HTN; androgen, restricted food intake, liver disease

Front 19

T/F Glucocorticoid feedback is the only controller of pituitary adrenocortical function

Back 19

F. It is a crude controller, determining the upper and lower levels of the system only. Doesn't appear to determine the patterns of pituitary-adrenal secretion which occur under basal and stress conditions.

Front 20

Under non-stress/basal conditions, what type of pattern does one see in plasma [cortisol]?

Back 20

Circadian/diurnal.


Highest in the morning, lowest in night.

[ACTH] is ahead of [cortisol] by about 15 minutes.

Hormone secretion occurs as episodic bursts.

This is also determined by activity pattern of individual (night shift workers will have different pattern).

Front 21

What is physiological definition of stress?

Back 21

Anything that evokes activation of pituitary-adrenocortical axis

Front 22

What does stress induced ACTH and subsequent cortisol release do to the hypothalamus?

Back 22

Results in release of CRH from hypothalamus

Front 23

What happens to hormone levels in prolonged stress?

Back 23

ACTH and cortisol levels are maintained (elevated) but not indefinitely. See a peak within 15 minutes, then a slow decline after about 30 minutes.


In chronic stress, ACTH and cortisol drop

Front 24

What is the amount of glucocorticoid in adrenal glands indicative of?

Back 24

Activity. The adrenal cortex does not store hormones

Front 25

What are the stimuli for aldosterone release?

Back 25

1) Decreased blood volume (major)
2) Electrolyte aberrations, like increased K+
3) Very high doses of ACTH
4) Sympathetic stimulation of kidney

Front 26

What activates the RAA?

Back 26

1) Decreased blood volume --> decreased Pa in renal artery --> sensed by juxtaglomerular (JG) cells.

2) JG cells increase renin secretion.

3) Meanwhile, maculadense monitors Na+ and Cl- filtration in distal tubules. Decreased delivery <b>also evokes increased renin secretion from JG cells.</b>

Front 27

After renin is secreted from JG cells, what happens?

Back 27

1) Renin converts angiotensinogen--> Angiotensin I

2) AI loses 2 amino acids via Angiotensin Converting Enzyme (ACE) --> AII

3) AII stimulates aldosterone release from zona glomerulosa.

Front 28

What is the alternate renin-angiotensin pathway?

Back 28

1) AI (decapeptide) is converted to a nonapeptide AI by aminopeptidase in plasma and tissues.

2) AI is converted to the heptapeptide (Des Asp1) AII (or AIII), by ACE.

3) AIII appears to be as potent as AII in <b>stimulating aldosterone release </b>but possess only <b>about 50% of its pressor activity.</b>

Front 29

What are representatives of the different steroid families produced by adrenal cortex?

Back 29

1) 21 carbon steroids : steroid nucleus (17 C always) + (18,19)methyls + 2 C sidechain. Ex. progestins, corticosteroids

2) 19 carbon steroids - steroid nucleus + (18,19)methyls. Ex. androgens (DHEA, testosterone)

3) 18 Carbon steroids - steroid nucleus + (18) methyl : estrogens

Front 30

Characteristics of steroidogenesis in z. glomerulosa

Back 30

Start with cholesterol.

- ACTH indpt (mostly)
- no 17&alpha; hydroxylase
- has 18&alpha; hydroxylase
- responsive to A2 and A3
- main product is aldosterone

Front 31

Characteristics of steroidogenesis in z. fasciculata and reticularis

Back 31

Start with cholesterol.

- no 18&alpha;-hydroxylase
- ACTH dept.
- 17&alpha; hydroxylase
- C17,20 lyase (for sex steroids)
- products are cortisol and sex steroids (no aldosterone)

Front 32

What is the site of ACTH action?

Back 32

Cholesterol side chain cleavage

Front 33

What is the function of C17,20 lyase?

Back 33

converts progestins to androgens

Front 34

What is corticosterone?

Back 34

Major secretory product of adrenal cortex.

Acts as an intermediate in the steroidogenic pathway from pregnenolone to aldosterone.

Exhibits both gluco- and mineralo-corticoid activities

Front 35

What is the desmolase reaction?

Back 35

Cholesterol side chain cleavage to &Delta;5-pregnenolone (21C) and isocaproic acid (6 carbons)

Site of ACTH action.

Front 36

What kind of compound is progesterone?

Back 36

&Delta;4, 3 ketosteroid (common feature of many steroid hormones)

Front 37

What is DOC?

Back 37

Intermediate in aldosterone synth pathway, between progesterone and corticosterone.

Potent mineralocorticoid

Front 38

What does aldosterone circulate as?

Back 38

Primarily as a hemiacetal

Front 39

What is aldosterone synthase?

Back 39

What 18 hydroxylase and 18-hydroxysteroid dehydrogenase are referred to as collectively

Front 40

What is the 17&alpha; hydroxylase pathway?

Back 40

Cortisol production by steroidogenesis in z. fasc. and ret.

Front 41

What is the main difference/similarities between sythesis of corticosterone and and cortisol?

Back 41

They follow the same set of enzyme reactions except cortisol is 17&alpha;-hydroxylated and corticosterone isn't

Front 42

What enzyme moves pregnenolone and progesterone over to the androgens and estrogen path?

Back 42

C17,20 lyase

Front 43

What is DHEA?

Back 43

Result when enzyme pregnenolone reacts with C17,20 lyase. It's a major source of androgen in women.

Front 44

What enzymes are also major enzymes in the gonads (testes and ovary)?

Back 44

17&beta;-hydroxysteroid dehydrogenase and aromatase

Front 45

What is the major reaction of corticosteroid hormone degradation?

Back 45

A-ring reduction: conversion of &delta;4,3 ketone

Front 46

What is pro-opiomelanocortin (POMC)?

Back 46

The peptide precursor of ACTH and related peptide hormones. All derived from proteolytic cleavage of this hormone

Front 47

What are effects of glucocorticoids (cortisol, corticosterone) on intermediary metabolism?

Back 47

Acts to elevate blood glucose
1) Protein breakdown
2) Carbohydrate metabolism
3) Lipid metabolism

Front 48

What do very high levels of glucocorticoids mimic?

Back 48

mineralocorticoids

Front 49

What are the cardiovascular effects of glucocorticoids?

Back 49

enhanced vascular reactivity to catecholamine; positive inotropic effect; elevate blood pressure

Front 50

What are the nervous system effects of glucocorticoids?

Back 50

When absent, slower EEG waves, decreased threshold to taste and smell stimuli.

Cortisol can cause euphoria, depression, psychotic episodes

Front 51

What are the gastrointestinal effects of glucocorticoids?

Back 51

Increase gastric acid and pepsin secretion (thus is contraindicated on people prone to ulcers)

Front 52

What are the skeletal muscle effects of glucocorticoids?

Back 52

In high doses, promote muscle wasting via protein catabolic effect

Front 53

What are the 2 glucocorticoids?

Back 53

Corticosterone, cortisol

Front 54

What are the compounds with mineralocorticoid effects?

Back 54

DOC, aldosterone, Corticosterone

Front 55

What will happen if the aldosterone pathway is blocked below the level of DOC? Above

Back 55

Mineralocorticoids still get produced; Above the level of DOC none is produced

Front 56

What are the adrenal androgens?

Back 56

DHEA and androstenedione

Front 57

What group do adrenal androgens have that allows them to be distinguished in urine?

Back 57

Ketone group at C17; called 17-ketosteroids

Front 58

What secretes CRH?

Back 58

paraventricular nuclei of hypothalamus.

Front 59

What is the dexamethasone suppression test?

Back 59

Dexamethasone is a synthetic glucocorticoid that has all the actions of cortisol including negative feedback on ACTH. It is more powerful than endogenous glucocorticoids.

When a low dose is given a healthy person, it inhibits ACTH secretion. This then inhibits cortisol secretion, which is measured.

The major use is for people with hypercortisolism.

It's used to determine whether it's primary (eg. cortisol secreting tumor) or 2ndary (ACTH secreting tumor).

If the cause is an ACTH-secreting tumor of anterior pituitary, a low dose of dexamethasone will not suppress cortisol release, but a high dose will.

If it's an adrenal cortical tumor, then neither high nor low dose will suppress.

Front 60

How does serum [K+] affect levels of aldosterone?

Back 60

Increases in K+ --> increase aldosterone secretion.

Aldosterone increases K+ secretion by kidney, thereby decreasing serum K+ towards normal.

Front 61

T/F glucocorticoids are essential life

Back 61

T

Front 62

What mediates the anti-inflammatory effect of glucocorticoids?

Back 62

Inhibits entire cascade associated with inflammation, including

-decreased vascular permeability
-decreased migration of cells
-decreased swelling of tissues
-increasing capillary resistance to infiltration

Mechanism:
-stabilization of lysosomal membranes which inhibits autolysis of cells when injured

Front 63

What are the effects of glucocorticoids on the immune system?

Back 63

1) Decreased eosinophils, basophils, and lymphoctyes

2) Decreases size of lymph nodes and thymus
-proliferation of some WBCs inhibited, induces apoptosis of some WBCs

3) Increased neutrophils, platelets and RBCs

They have a <b>general immunosuppressive effect</b>.

Front 64

Glucocorticoid effects on water metabolism

Back 64

Involves 2 opposing actions

- increased GFR promoting excretion of water
- mineralocorticoid effect that promotes fluid retention

Front 65

What promotes Na+ reabsorption in exchange for K+ and H+ excretion in the distal tubules/collecting ducts?

Back 65

aldosterone

Front 66

What provides a major anabolic component in the female?

Back 66

Adrenal androgens

Front 67

What are the molecular mechanisms of corticosteroid action?

Back 67

A) Corticosteroids enter cells and bind cytosolic or nuclear intracellular receptors

B) Receptor-corticosteroid complex interacts with genome at glucocorticoid response element (GRE).

3) Transcription altered -> affects what proteins get made

Front 68

What is the action of aldosterone in kidney epithelial cell?

Back 68

1) Increased passive diffusion of Na+ across luminal membrane into cells, which is countered by:
2) Activation of Na+/K+/ATPase on serosal membrane which pumps Na+ into ECF.
3) Increased luminal negativity relative to cell resulting from Na internalization promoting tubular secretion of K+ and H+.

Front 69

What are Type I receptors?

Back 69

They allow both mineralocorticoids and glucocorticoids to pass, but they are used by mineralocorticoids.

The specificity is mediated by the fact that mineralocorticoid targets have 11&beta;-hydroxysteroid dehydrogenase, that converts costisol to cortisone (cortisone has LOWER AFFINITY for type I receptors)

Aldosterone isn't transformed by this enzyme.

Front 70

Since Type I receptors don't discriminate between gluco-and mineralocorticoids, but only mineralocorts use them, how do they allow this?

Back 70

The specificity is mediated by the fact that mineralocorticoid targets have enzyme 11β-hydroxysteroid dehydrogenase, that converts costisol to cortisone (cortisone has LOWER AFFINITY for type I receptors)

Aldosterone isn't transformed by this enzyme.

Front 71

What are Type II receptors?

Back 71

They mediate glucocorticoid effects

Front 72

What are the 2 etiologies of Cushing syndrome?

Back 72

1) Primary hypercortisolism - excess cortisol secreted by adrenal tumor

2) Secondary hypercortisolism - high cortisol due to high ACTH (from tumor etc.)

Front 73

What is the pattern of cortisol and ACTH in a) primary and b) secondary hypercortisolism?

Back 73

A) Low ACTH (from neg fb), High Cortisol

B) High cortisol, High ACTH

Front 74

Clinical signs of Cushing syndrome

Back 74

A) Muscle wasting
B) Poor wound healing, thin skin
C) Central obesity fat distribution, moon face and buffalo hump
D) Hyperglycemia
E) Hypertension
F) Virilization in females/facial hirsutism/acne
G) Psychotic episodes and depression
H) GI problems/ulcers
I) Poor resistance to infection due to anti-inflammatory actions

Front 75

What are the 2 etiologies of hypocortisolism?

Back 75

1) Primary hypocortisolism (Addison's disease) -lesions in adrenals or deficiencies in steroidogenic enzymes.

2) Secondary hypocortisolism - may result from panhypopituitarism, ACTH deficiency, involves atrophy of z fasciculate or reticularis

Front 76

What is Congenital Adrenal Hyperplasia?

Back 76

Another form of hypocortisolism. Results from deficiency in steroidogenic enzyme within the adrenal cortex, producing impairment in cortisol secretion.

Adrenal hyperplasia comes from hypersecretion of ACTH.

Front 77

What happens in the cholesterol desmolase deficiency form of CAH?

Back 77

Congenital adrenal "lipoid" hyperplasia.

Involves impaired conversion of cholesterol to prenenolone, leading to general steroid deficiency. Not compatible with life.

Front 78

What happens in the 3 &beta;-hydroxysteroid dehydrogenase deficiency form of CAH?

Back 78

Neither form of prenenolone can be converted to either form of progesterone.

There is an overproduction of DHEA, the one pathway that doesn't use this enzyme (aldosterone and cortisol do). <b>Virilization effects - called "adrenogenital syndrome"</b>

Aldosterone deficiency leads to sodium loss and low blood pressure.

Front 79

What happens in the 21-hydroxylase deficiency form of CAH?

Back 79

This is most common form of CAH. Neither progestin can be converted to DOC or deoxycortisol.

No aldosterone or cortisol.

Since Progestin can be made, there is increased production of BOTH DHEA and Androstenedione (causing virilization)

Front 80

What happens in the 11&beta;-hydroxylase deficiency form of CAH?

Back 80

This one is rare. Conversion of A) DOC to corticosterone and B) deoxycortisol to cortisol are both impaired.

Results in buildup of DOC, a potent mineralocorticoid (causes hypertension, hypokalemic alkalosis).

Front 81

What happens in the 17-&alpha; hydroxylase deficiency form of CAH?

Back 81

CAH without adrenogenital effects.

Phenotype is excess mineralocorticoid (hypertension, hypokalemic alkalosis) - but LOW ALDOSTERONE because RAA system is surpressed. Female phenotype at birth