Lecture 18: Adrenals Flashcards
Adrenal gland layers
- Capsule
Cortex: - Zona glomerulosa (aldo.)
- Zona fasciculata (cortisol)
- Zona reticularis (androgens; DHEA + androstenedione)
- Medulla (catecholamines)
Adrenal tissue
Medulla = neural tissue, SNS stim.
Cortex = glandular tissue, var. stims.
Adrenal blood flow
Blood flows from capsule to medulla, meaning cortical hormones will affect the medulla
i.e. cortisol -> PMNT for NE to epi conversion
Blood transporters for adrenal cortex hormones
All cortical hormones are steroids.
- Cortisol -> CBG
- Aldosterone -> albumin, CBG
- Androgens -> albumin, SHBG
Cortisol
- Synthesized via StAR activation (rate limit. for all steroid hormones)
- ACTH follows circadian rhythm; highest early morning
- Increases blood glucose (liver gluconeogen., adipose lipolysis, muscle glycogenolysis)
- Increases muscle/adipose gluc. uptake
- Binds mineralocorticoid receptor
Cushing’s Syndrome/Disease
Hypercortisolism; can be due to exogenous medication or hypersecretion. Over time, low ACTH -> zona f./r. atrophy
Aldosterone
- Promotes Na/H2O reabsorp., K+ excretion (RAAS); acts on DT/CD channels
- Binds mineralocorticoid receptor (MR; cortisol too)
11beta-hydroxysteroid DH
- Found in target cells for aldosterone; inactivates cortisol and prevents cortisol MR overactivation
Apparent Mineralocorticoid Excess
Caused by 11beta HSDH defect (black licorice poisoning) -> hypertension, hypokalemia
HPA axis loophole
ACTH -> cortisol, androgen production by adrenals but androgens DON’T neg. fb on ACTH
DHEA-S
Highest in fetus, puberty
- Stim. pubic/axillary hair, bone/muscle form., CV/repro health esp. post menopause
- Converted to DHT, T (sebaceous glands, adipocytes)
Addison’s Disease
Autoimmune primary adrenal insufficiency
- Loss of cortisol/aldo.
- High ACTH -> melanin production from melanocyte receptors
Congenital Adrenal Hyperplasia
Primary adrenal insufficiency; enzyme Mx blocks hormone production
- Hyperplasia due to high ACTH trophic effects
- Production can be redirected to other steroids
Adrenal medulla catecholamines
Chromaffin cells synth. NE from Tyr -> PMNT converts NE to E
- Cortisol determines NE/E ratio
- Epi/NE very very short half life; degraded by MonoAmine Oxidase + COMT
Catecholamines in plasma/receptors
Catecholamines 50% free 50% bound to albumin; 10-15 sec. half life
Bind alpha/beta adrenergic GPCRs for fight/flight
Pheochromacytoma
Functional chromaffin cell tumor; increased catecholamine synth./release
