HRR: adrenal cortex Flashcards
What are the zones of the adrenal cortex?
Glomerulosa, fasciculata, and reticularis
ACTH stimulates which portions of the adrenal cortex?
Zona fasciculata and zona reticularis
What is the starting point for steroid synthesis?
C27
What is desmolase?
An enzyme that cleaves carbons from cholesterol to help us derive various hormones
ACTH stimulates the uptake of…
LDL cholesterol
What is STAR?
A protein that transfers cholesterol into the inner mitochondrial membrane
Describe cholesterol entering the zona fasciculata.
- ACTH stimulates uptake of LDL cholesterol
- Cholesterol is esterified and taken into a vesicle
- Cholesterol ester hydrolyase forms free cholesterol
- STAR transfers free cholesterol to the inner mitochondrial membrane
What are rate-limiting enzymes of steroid synthesis?
Desmolase and StAR
What is formed from cholesterol via initial cleavage by desmolase?
Pregnenolone (C21)
What does 17-hydroxylase do?
Adds a hydroxyl group to pregnenolone in the zona fasciculata
What does 21-hydroxylase do?
Forms 11-deoxycortisol from 17OH-progesterone
What does 11-hydroxylase do?
Forms cortisol from 11-deoxycortisol in the zona fasciculata
What does 11B HSD type 2 do?
Breaks cortisol to cortisone, forming an inactive metabolite. This prevents cortisol from setting off too many mineralocorticoid receptors when it shouldn’t
Where do we have a lot of 11B HSD type 2?
Kidney and colon (where there’s lots of mineralocorticoid receptors)
What does 11B HSD type 1 do?
Forms cortisol from cortisone, the active version. This allows us to utilize cortisol at mineralocorticoid receptors when we want to.
What cofactor enhances the 17-hydroxylase complex?
B5
What are DHEA, DHEAS, and androstenedione?
Weak androgens that are converted by other tissues to be more potent androgens such as testosterone
17OH-pregnenolone can be acted on by 17-hydroxylase to form…
DHEA
What does SULT2A1 do?
Form DHEAS from DHEA
Where do we make most testosterone?
Most is in the peripheral tissues; some is made in the zona reticularis!
DHEA can form…
Androstenedione and testosterone
What are binding proteins for cortisol?
CBG and albumin
How is bound cortisol used?
It is not! It is still measured in total cortisol
What are the functions of binding cortisol?
Stabilizes the hormone, decreases metabolism/extends half-life, creates a reservoir
What receptors does cortisol bind?
Intracellular glucocorticoid receptor alpha and mineralocorticoid receptors
How does cortisol impact metabolism?
Increases blood glucose and glycogen storage, increases insulin resistance, promotes protein breakdown/decreases synthesis, and increases fat breakdown
What are body-habitus effects of cortisol?
“Moon face”, fat deposition in the trunk, and muscle wasting/thin limbs
What are cardiovascular effects of cortisol?
Helps maintain BP by acting as a permissive hormone for catecholamines and angiotensin II
What is the role of cortisol in inflammation?
It is anti-inflammatory, and acts to depress cytokines, histamines, prostaglandins
What is the role of cortisol in terms of the immune response?
It limits circulating lymphocytes and antibody production
Describe how cortisol is anti-inflammatory.
When Tissue injury occurs, NFkB translocates to the nucleus and causes genes that encode for pro-inflammatory cytokines, leukotrienes, TNFa, etc to be transcribed. Cortisol binds GR receptors, enters the nucleus, and the complex lands on the genes NFkB targets, blocks its effects. Cortisol thereby decreases release of pro-inflammatory chemical mediators
What is Addison’s disease?
Adrenal gland loss associated with bronzing of the skin/hyperpigmentation, general fatigue, and heart symptoms from increased ACTH
What is Cushing’s disease?
Overproduction of ACTH and cortisol leading to loss of musculature and muscle weakness, truncal obesity, hyperglycemia, and hypertension
