Adrenal Physiology

Question 1

What regions of the adrenal cortex releases glucocorticoids?

Answer 1

Zona fasciculate (75%)
and
Zona reticularis

Cortisol and corticosterone

Question 2

What regions of the adrenal cortex releases mineral corticoids?

Answer 2

The zona glomerulosa

Aldosterone

Question 3

What regions of the adrenal corext releases androgens?

Answer 3

Zona reticularis

Question 4

What regions of the kidney release catecholamines?

Answer 4

Adrenal medulla

Question 5

What components make up the HPA axis?

Answer 5

Paraventricular nucleus of the hypothalamus
The anterior pituitary
Adrenal cortical cells

Question 6

What are triggering signals for Glucocorticoid synthesis?

Answer 6

Emotional stress, hypotension, hypertension and hypoglycemia.

Question 7

What is the signalling cascade for release of glucocorticoid steroids?

Answer 7

Hypothalamus releases CRH through the venous plexus to the anterior pit where ACTH and Melanocyte stimulating hormone is made from precursor POMC.

Question 8

What provides negative feedback to the glucocorticoids?

Answer 8

Cortisol binds Glucocorticoid receptor in the cytoplasm of the corticotroph cells of the anterior pit and CRH secreting neurons in the hypothalamus reducing release of CRH and ACTH.

Question 9

What is the core reasoning for ACTH?

Answer 9

ACTH binds to MCR2R (melanocortin 2 receptor)

MCR2 causes increase in PKA leading to chosterol ester hydrolase activation elevating free cholesterol feeding.

This all leads to increased cholesterol desmolase synthesis via StAR synthesis!

Core regulator of androgen and glucocorticoid synthesis.

Question 10

What effect would not having 17-alpha hydroxylase cause?

Answer 10

It is key to forming both glucocorticoids and androgens without it neither cortisol or testosterone could be made.

Question 11

What effect would not having 21-hydroxylase cause?

Answer 11

21 hydroxylase is essential for forming both cortisol and aldosterone and without it you would not have either.

Question 12

What role does 17-20 lyase have?

Answer 12

It is essential for androgen formation from DHEA

DHEA is then converted by 3B-hydroxysteroid dehydrogenase into Testosterone.

Question 13

What specifically does 21-hydroxylase form?

Answer 13

Forms 11 deoxycortisol which is used in forming cortisol and aldosterone.

Question 14

What is the function and physiological significance of 11B-hyrdroxysteroid dehydrogenase type 2?

Answer 14

Cortisol is able to bind mineral corticoid receptors like aldosterone but there is much more cortisol.

11B-HSD type II prevents over activation by converting cortisol into cortisone while not acting on aldosterone.

Question 15

What occurs in cushings syndrome?

Answer 15

This is the case in which 11B-HSD2 becomes saturated due to a build of of cortisol with an overdose of glucocorticoid treatment leading to hypertension and hypokalemia.

Question 16

What is released by the adrenal medulla? What cell type?

Answer 16

Chromafin cells release catecholamines norepinephrine, epinephrine, and dopamine when stimulated by sympathetics releasing Ach.

Question 17

What is the synthesis steps of making catecholamines?

Answer 17

Tyrosine hydroxylase + L-tyrosine = L-Dopa *Rate limiting

L-aromatic amino acid decarboxylase (AAAD) + LDOPA = Dopamine

Dopamine + Dopamine-B-hydroxylase = Norepinephrine.

Question 18

How is norepiephrine specifically made?

Answer 18

Dopamine + Dopamine-B-Hydroxylase = norepinephrine.

Question 19

How is epinephrine specifically made?

Answer 19

PNMT (phenylethanolamine-N-methyltransferase converts norepinephrine that leaves vesicles.

Question 20

How does cortisol effect PNMT?

Answer 20

PMNT expression is upregulated by cortisol!

Question 21

What deficiency would be seen in the adrenal medula following a cortisol deficiency?

Answer 21

A deficiency in Epinephrine (adrenaline)

As PMNT expression is upregulated by cortisol.

Question 22

How is norepinephrine and epinephrine catabolized when they leak out of vesicles?

Answer 22

Norep. gets catalized to normetanephrine
Epinephrine gets catalized to metanephrine
these both enter the circulation and are urinated out.`

Question 23

What are catecholamines catabolized into when used by cells?

Answer 23

Cells metabolize them into vanillylmandelic acid (VMA) where they will be excreted in the urine.

Question 24

What receptor type does norepinephrine work stronger on?

Answer 24

Alpha receptors

Question 25

What receptor type does epinephrine have a stronger affinty for?

Answer 25

Beta receptors
Think bronchial smooth muscle dilation
Liver and skeletal muscles better used during exercise.

Question 26

What are the side effects of 21 hydroxylase deficiency?

Answer 26

Progesterone and 17 alpha-hydroxyprogesterone cannot be converted to form aldosterone and cortisol.

Thus androgens are made instead and an increase in 17-OH progesterone would be seen.
Causes less ACTH secretion inhibition leading to adrenal hyperplasia leading to even more adrenal androgen production!

See male genitalia in females, salt wasting, young males with adult genitalia.

Question 27

What is primary adrenal insufficiency (addisons disease)?

Answer 27

Disfunction of the adrenal cortex (autoimmune distruction)

Deficiency of cortisol and aldosterone.
Elevated levels of CRH and ACTH

Symptoms: Postural hypotension, hyponatremia, hyperkalemia, hypoglycemia and difuse darkening of the skin or spotty pigmentation due to POMC from ACTH elevation.

Treat with cortisone.

Question 28

What causes secondary adrenal insufficiency?

Answer 28

Supression of ACTH induced cortisol production due to hypothalamic or pit disorders.

Aldosterone is not efected as it is regulated by ANG II and K+ levels thus mineralcorticoid treatment not necessary.