Adrenal gland

Gross anatomy

Overview

Function

Vasculature

  • Arterial blood supply
    • Superior suprarenal artery (from the inferior phrenic artery)
    • Medial suprarenal artery (from the abdominal aorta)
    • Inferior suprarenal artery (from the renal artery)
  • Venous drainage
    • Right suprarenal vein into the inferior cava vein
    • Left suprarenal vein into the left renal vein
  • Lymph drainage: left aortic lymph nodes; right caval lymph nodes

The left suprarenal vein merges into the left renal vein; the right suprarenal vein merges directly into the inferior vena cava!

Innervation

Microscopic anatomy

Adrenal cortex

GFR → MGA = The layers of the adrenal cortex from outside to inside are GFR (G = Zona Glomerulosa, F = Zona Fasciculata, R = Zona Reticularis). They are the Managing General Agents of some hormone synthesis.

Adrenal medulla

The cells of the adrenal medulla are modified sympathetic cells that are controlled by cholinergic synapses.

Hormones of the adrenal cortex

Common synthesis pathway for all steroid hormones: cholesterol (precursor) → pregnenolon via cholesterol desmolase

Hormone Site of production Function Feedback control Associated disorders

Mineralocorticoids: aldosterone

  • Regulation of renal sodium and water reabsorption and potassium excretion
  • See the section “Mineralocorticoids” below for details
Glucocorticoids: cortisol

Androgens: dehydroepiandrosterone (DHEA)

Going from outside to inside, the hormones produced in each layer: The deeper you go, the sweeter it gets: Salt (Na+ and mineralcorticoids, zona glomerulosa), Sugar (glucocorticoids, zona fasciculata), and Sex (androgens, zona reticularis)

The RAAS regulates the release of mineralocorticoids!

Mineralocorticoids

General

Synthesis

Biosynthesis of aldosterone
Steps

Precursor

Enzyme Product
1.
  • Pregnenolone
  • 3β-hydroxysteroid dehydrogenase
  • Progesterone
2.
  • Progesterone
  • 11-deoxycorticosterone
3.
  • 11-desoxycorticosterone

  • Corticosterone
4.
  • Corticosterone

Regulation: renin-angiotensin-aldosterone system (RAAS)

Function

  • Mechanism: binds to intracellular mineralocorticoid receptors in the distal tubule and collecting duct of the kidney
    • Na+/K+-ATPase in the basolateral membrane → transports Na+ out and K+ into the tubule cells
    • Apical H+-ATPase
    • ↑ Na+ channels ENaC (epithelial natrium channel) and K+ channels ROMK (renal outer medullary potassium channel) in the luminal membrane
  • Effect: ↑ Na+ resorption; ↑ H2O resorption; ↑ K+ excretion; ↑ H+ excretion → extracellular fluid, ↑ blood pressure, ↓ K+, ↑ pH

Aldosterone stimulates the sodium and water retention and potassium excretion in the kidney!

Glucocorticoids

General

Synthesis

Steps Precursor Enzyme Product
1. Pregnenolone pathway Pregnenolone
  • 17α-hydroxylase
  • 17-hydroxypregnenolone
Progesterone pathway Pregnenolone
  • 3β-hydroxysteroid dehydrogenase
  • Progesterone
2. Pregnenolone pathway 17-hydroxypregnenolone
  • 3β-hydroxysteroid dehydrogenase
  • 17-hydroxyprogesterone
Progesterone pathway
  • Progesterone
  • 17α-hydroxylase
3. Common pathway
  • 17-hydroxyprogesterone
  • 11-deoxycortisol
4. Common pathway
  • 11-deoxycortisol


Regulation: hypothalamic-pituitary gland-adrenal cortex feedback mechanism

Cortisol inhibits the secretion of CRH and ACTH via negative feedback, which, in turn, results in a decrease in cortisol secretion.

Function

Androgens

General

In both men and women, DHEA and androstenedione are produced in the adrenal cortex, which are precursors for testosterone and estrogen. Testosterone is produced by Leydig cells in the testes in men and, to a lesser degree, ovarian stroma in women.

Synthesis

Regulation: hypothalamic-pituitary gland-adrenal cortex feedback mechanism

Function

Generally, the effects of androgens in women only become apparent in cases of androgen excess (e.g., PCOS, androgen-secreting tumors).

Hormones of the adrenal medulla: Catecholamines

General

Synthesis

Step

Precursor

Enzyme

Product

1. 1st Hydroxylation

Phenylalanine

Tyrosine

2. 2nd Hydroxylation

Tyrosine

DOPA (3,4-Dihydroxyphenylalanine)

3. Decarboxylation

DOPA

Dopamine

4. Hydroxylation of the β-C-Atom

Dopamine

Norepinephrine

5.Methylation

Norepinephrine

  • Phenylethanolamine-N-Methyltransferase (PNMT)
  • Cofactor: S-Adenosylmethionine (SAM)

Epinephrine

Epinephrine has the shortest half-life of the catecholamines.

Stress results in an increased production of catecholamines and glucocorticoids.

Degradation

The end-stage metabolite of epinephrine and norepinephrine is vanillylmandelic acid. Urinary excretion of VMA has diagnostic value in pheochromocytoma and neuroblastoma!

Function

Overview of peripheral adrenergic receptors

Receptor

G protein Signal transduction

Location

Effect

α1

Gq Stimulation of phospholipase C: PIP2IP3 und DAG → ↑ Ca2+
  • ↑ Contraction of smooth musclesvasoconstriction
  • ↑ Constriction of sphincters

α2

Gi Inhibition of adenylate cyclase: ↓ cAMP
  • Lipolysis
  • ↓ Muscular contraction

β1

Gs Stimulation of adenylate cyclase: ↑ cAMP
  • Heart rate
  • ↑ Contractility
  • ↑ Conductivity

β2

  • Vasculature (coronary vessels, skeletal muscles)
  • Bronchi
  • ↓ Contraction of smooth musculature → vasodilatation and bronchodilatation
  • Glycogenolysis
  • Lipolysis
  • Uterus

β3

  • Brown adipose tissue
  • Lipolysis

Clinical significance

Important diseases associated with the adrenal cortex

Important diseases associated with the adrenal medulla

  • Abdel-Rahman MY. Androgen Excess Workup. In: Lucidi RS. Androgen Excess Workup. New York, NY: WebMD. http://emedicine.medscape.com/article/273153. Updated August 1, 2016. Accessed February 12, 2017.
  • Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017.
  • Rotstein A. Sex Hormone Synthesis, Regulation, and Function. http://www.pathophys.org/sexhormones/. Updated January 1, 2018. Accessed November 21, 2018.
last updated 12/03/2018
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