Adrenal Glands Flashcards
(27 cards)
What are the origins of the two Adrenal Glands and what do they secrete?
- Medulla: neuroectodermal origin that secretes catecholamines, NE and EN
- Cortex: mesodermal origin with 3 layers that secrete corticosteroids
What are the corticosteroids of the adrenal cortex?
- mineralcorticoids: aldosterone
- glucocorticoids: cortisol
- androgens: testosterone
What are the peptides formed from the preprohormone POMC and their function?
- ACTH: cortisol release
- a-MSH: skin pigmentation and appetite
- B-endorphin: inhibit pain sensitivity
How is Cortisol and Aldosterone transported in the blood?
- cortisol is mostly tightly bound to CBG (90-95%) —> slow elimination and longer half life (60-90min)
- 60% of aldosterone is bound to albumin —> other 40% is free, active and shorter half life (20 min)
- both have slow onset, long duration of action
What is the action of Cortisol and Aldosterone inside the target cell?
- Hormone released from protein → diffuses into target cell
- Binds to intracellular receptor in the cytosol
- Forms a hormone–receptor complex
- Complex undergoes dimerization
- Dimerized complex enters the nucleus and binds to glucocorticoid response elements (GREs) on DNA
- Triggers transcription → mRNA → protein synthesis
How are Cortisol and Aldosterone cleared?
After action, adrenal steroids are conjugated to:
- Glucuronic acid or sulfates then excreted through bile or kidney
What is the release pattern of Cortisol?
dinural pulsatile release with the highest in the morning and lowest at night before bed
What is the rate-limiting step of adrenal hormone biosynthesis?
first and slowest step where cholesterol desmolase (stimulated by ACTH) converts cholesterol into pregnenolone
Where does most of the cholesterol come from thats used for biosynthesis of adrenal hormones?
most comes from the bloodstream and the receptors on adrenal cells that help import cholesterol are:
- LDL receptor (LDLr): imports cholesterol from LDL
- SR-B1 receptor: binds HDL for cholesterol import
What are the enzymes of each of the specific zones for specific adrenal hormone synthesis?
- Zona glomerulosa: Aldosterone synthase→ Aldosterone (stimulated by Angiotensin II and ↑ K⁺)
- Zona fasciculata: 21β-, 11β-hydroxylase → Cortisol
- Zona reticularis: 17,20-lyase → Androgens (e.g., DHEA, androstenedione)
What is the difference in adrenal androgen activity, DHEA and androstenedione, in males and females?
- in males they are considered weak bc the testes produce more potent androgens like testosterone and dihydrotestosterone (DHT)
- in women adrenal androgens are a major source of androgens in women
What is the regulation mechanisms of the zona fasciculata and reticularis?
PVN of the hypothalamus releases CRH → acts on corticotrophs (AP) via adenylyl cyclase → cAMP pathway → ACTH → adrenal cortex → cortisol and adrenal androgens
What is the feedback mechanism of the zona fasciculata and reticularis?
excess cortisol exerts negative feedback at:
- Hypothalamus → reduces CRH release
- Anterior pituitary → reduces ACTH release
- Hippocampus → modulates hypothalamic response
What does chronic release of ACTH cause?
Chronic ACTH elevation → causes adrenal cortex hypertrophy → trophic effect is partly mediated by somatomedins (like IGF-2)
What are the reasons the Zona glomerulosa does not produce glucocorticoids?
- aldosterone synthase converts corticosterone into aldosterone
- ZG lacks 17,a-hydroxylase and is unable to convert progesterone to cortisol
what happens if there’s a block at or above 21β-hydroxylase?
mineralocorticoids like aldosterone cannot be produced which leads to salt-wasting disorders
What are the stimulatory and inhibitory factors that affect ACTH release?
- stress, hypoglycemia, trauma simulate
- drugs inhibit or stimulate
- somatostatin inhibits
What are the actions of Glucocortcoids?
- catabolic and diabetogenic effect
- hyper/hypoglycemia in excess or deficiency
- increase glomular filtration rate (vasodilation)
- decreased REM (increases wake time)
- up-regulate a1-adrenergics (vascular tone)
How do glucocorticoids have an anti-inflammatory effect and what will this lead to?
- cortisol induces lipocortin synthesis → inhibits phospholipase A2
- cortisol inhibits IL-2 and T cell proliferation
- inhibits the release of histamine and serotonin
***suppresses the immune system
What causes Crushing syndrome and what are the results?
hypersecretion of cortisol including pituitary adenoma → increase in ACTH or by exogenous administration of glucocorticoids
- over production of adrenal androgens ( problem for women)
- obesity, hyperglycemia, poor wound healing etc
What causes Addison’s Disease and what are the results?
primary adrenocortical insufficiency of ALL adrenocortical hormones caused by auto-immune destruction
- hypoglycemia, hypotension, metabolic acidosis etc
What are the stimulus for the release of aldosterone?
- ACTH
- AngII
- Increased K+
What is the pathway for aldosterone release caused by hyperkalemia?
High extracellular K⁺ causes:
- Depolarization of adrenal zona glomerulosa cells
- Opening of voltage-gated calcium channels
- ↑ Intracellular calcium activates aldosterone synthase
What is the pathway for aldosterone release caused by ACTH?
ACTH enhances:
- activity of aldosterone synthase (the final enzyme that makes aldosterone)
- number of LDL receptors on the adrenal cell membrane → brings in more cholesterol for hormone synthesis
