Adrenal Gland

Question 1

What hormone is produced in the zona glomerulosa?

Answer 1

aldosterone

Question 2

What 2 hormones are produced in the zona fasciculata?

Answer 2

cortisol/corticosterone (glucocorticoids)

-some DHEA

Question 3

What hormone is produced in the zona reticularis?

Answer 3

DHEA

androstenedione

Question 4

___(1)____ transports cholesterol in to ___(2)___ to begin synthesis pathway for adrenal hormones?

Answer 4

1. StAR: Steroidogenic acute regulator protein
   - -RATE LIMITING STEP OF CHOLESTEROL BIOSYNTH
2. Mitochondria

Question 5

How does de novo cholesterol biosynthesis begin? (extra/intracellular)
what receptors?

Answer 5

1. extracellular cholesterol is picked up in the form of HDL and LDL

LDL: LDLR
HDL: SRB1

2. intracellular: de novo synthesis from fatty acids

Question 6

What 3 things upregulate StAR?

Answer 6

1. LH
2. IGF-1
3. Insulin

Question 7

Why is it possible for androgens to be overproduced?

Answer 7

Androgens dont negatively feedback on the HPA axis

Question 8

What receptor on the adrenal glands does ACTH binds to, to produce cortisol and androgens?

Answer 8

melanocortin-2 receptor (MC2R)

-cAMP is secondary messenger

Question 9

What 3 things regulate aldosterone secretion? (slow genomic, and fast nongenomic mechanisms)

Answer 9

1. ACTH (slow genomic)
2. Angiotensin II (fast non-genomic)
3. local potassium levels (fast non-genomic)
   - -high K in extracellular fluid increases aldosterone

Question 10

What are 3 main results of aldosterone acting on the kidneys?

Answer 10

1. reabsorption of sodium (active) and water (passive)
2. secretion of K (principal cells)
3. Secretion of acid (intercalated cells)

Question 11

What is the sequence of the RAAS system?

Answer 11

1. volume loss, Na+ deficiency
2. Juxtaglomerular cells release renin
3. renin activates angiotensinogen (prod in liver) into angiotensin I
4. Angiotensin I converted into angiotensin II in lungs
5. Angiotensin II constricts arterioles + signals to adrenal cortex to produce aldosterone

Question 12

What two biochemical pathways occur in adrenocortical cells to release aldosterone? (angiotensin II, potassium)

Answer 12

angiotensin 2: Phospholipase C -> IP3 -> Ca2+

potassium: depolarize cell -> increase Ca2+

Question 13

What is and is not a negative feedback for the CRH and ACTH release?

Answer 13

Glucocorticoids = negative feedback

Aldosterone - DO NOT negatively feedback

Question 14

What is the inhibitory regulation of aldosterone?

Answer 14

Increased BP -> ANP release

-inhibits Zona glomerulosa

Question 15

How do Glucocorticoids interact with cells?

Answer 15

bind to CYTOSOLIC glucocorticoid receptor (GR)

-translocates to nucleus: binds to glucocorticoid response elements (GRE)

Question 16

What 5 things are regulated by glucocorticoids (cortisol)

Answer 16

1. Immune
2. Development
3. Body fluid homeostasis
4. Metabolic
5. Arousal/cognition

Question 17

What part of the hypothalamus releases CRF?

Answer 17

paraventricular nucleus

Question 18

How is cortisol usually transported through the blood?

Answer 18

90% bound to corticosteroid-binding globulin [CBG] - “transcortin”

5%albumin

5% free cortisol

Question 19

What is the predominant site of steroid inactivation? what is the mechanism of action?

Answer 19

liver
conjugation of steroids with:
1. Glucuronide
2. Sulfate
 = more readily excreted by the kidney

Question 20

What are two causes of CRH release?

Answer 20

1. Diurnal rhythm (rises in morning before waking)

2. Stress (physical, emotional, biochemical)

Question 21

What is the biochemical pathway for cortisol release after ACTH binds MC2R?

Answer 21

cAMP
PKA
Cortisol synthesis

Question 22

Besides ACTH release, What else can CRH stimulate?

Answer 22

gene transcription of precursor pro-opiomelanocortin (POMC)

POMC is precursor to: MSH, ACTH, B-endorphins

Question 23

What proinflammatory cytokines can stimulation ACTH production?

Answer 23

IL-1
IL-6
TNFa

Question 24

What psychological disorder is a/w high cortisol?

Answer 24

depression

-consider as a Sx of cushings

Question 25

What are 4 metabolic fx of Glucocorticoids?

Answer 25

Causes:

1. Hyperglycemia (increased gluconeogenesis, glycogenolysis)
2. FFA and Amino acid production
3. Catecholamine release and tissue sensitivity to catecholamines
4. Anti-inflammatory/immunosuppressive

Question 26

What two hormones regulate androgen production?

Answer 26

ACTH

Cortical androgen stimulating hormone (CASH)

Question 27

What is the normal physiological effect of DHEA on testes? high dose?

Answer 27

normal: promotes spermatogenesis and maturation of sperm

High dose: testicular atrophy (inhibits GnRH)

Question 28

What is the affect of DHEA on a fetus?

Answer 28

HCG causes release of testosterone
testosterone promotes dev of male reproductive tract:
1. internal genitalia
2. vas deferens
3. epididymis
4. external genitalia

Question 29

What are the two most common enzyme deficiencies in steroid hormone synthesis?

Answer 29

1. 21-a-hydroxylase deficiency

2. 11-B-hydroxylase deficiency

Question 30

What happens in 21-a-hydroxylase deficiency?

Answer 30

1. absent aldosterone and cortisol

2. lots of androgens

Question 31

What happens in 11-B-hydroxylase deficiency?

Answer 31

1. low cortisol, aldosterone, corticosterone
   - -increased production of deoxycorticosterone causes fluid retention (suppresses RAAS system)
2. lots of androgens