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Adrenal gland

Last updated: September 7, 2021

Summarytoggle arrow icon

The adrenal gland is a paired retroperitoneal organ located on the upper pole of each kidney. It receives its arterial supply from the superior, middle, and inferior suprarenal arteries and drains into the right and left suprarenal veins. The lymphatics drain into the left aortic and the right caval lymph nodes. The adrenal gland has two layers: the adrenal cortex (outer layer), which is derived from the mesoderm, and the adrenal medulla (inner layer), which is derived from neural crest cells. The adrenal medulla is composed of chromaffin cells, which secrete catecholamines (norepinephrine, epinephrine, dopamine). The adrenal cortex consists of three layers: the zona glomerulosa, the zona fasciculata, and the zona reticularis, which are responsible for the synthesis of mineralocorticoids, glucocorticoids, and androgens (precursors for estrogen and testosterone), respectively. Mineralocorticoids regulate renal sodium and water reabsorption and potassium excretion, while glucocorticoids play an important role in glucose metabolism. Diseases of the adrenal glands include adrenal insufficiency (due to an infection, hemorrhage, or autoimmune destruction), hyperaldosteronism (due to hyperplasia or adenoma), and hypercortisolism (due to hyperplasia, adenoma, or exogenous administration).

Overview

Function

Blood supply and lymphatics

Because the adrenal glands produce and subsequently release a number of essential hormones, they are very well vascularized and perfused.

Venous drainage is different for the left and right adrenal gland. The left suprarenal vain empties into the left renal vein, while the right suprarenal vein drains into the inferior vena cava.

Innervation [3]

Adrenal cortex

To remember the microscopic anatomy and functions of the adrenal cortex going from outside to inside, think “GFR, the deeper you go, the sweeter it gets: Salt (aldosterone, zona Glomerulosa), Sugar (glucocorticoids, zona Fasciculata), and Sex (androgens, zona Reticularis).

Adrenal medulla

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

Synthesis of all steroid hormones begins with the common precursor molecule, cholesterol, which is converted into pregnenolone via cholesterol desmolase. Cholesterol desmolase can be inhibited by azole antifungals.

Overview of the hormones of the adrenal cortex
Features

Aldosterone

Cortisol

Dehydroepiandrosterone (DHEA)

Hormone class
Production site
Function
Regulation of secretion
Associated disorders

RAAS regulates the release of mineralocorticoids.

Mineralocorticoid synthesis

Biosynthesis of aldosterone
Steps

Precursor

Enzyme Product
1.
  • 3β-hydroxysteroid dehydrogenase
2.
  • 21-hydroxylase
3.
  • 11-deoxycorticosterone

4.
  • Corticosterone
  • Aldosterone synthase

Mineralocorticoid function

  • Effects
    • These aldosterone-induced changes produce a concentration gradient → Na+ reabsorption → water reabsorption and K+ secretion into the urine.
    • Ultimately, these effects → blood pressure, hypokalemia, and pH level.

Aldosterone stimulates potassium excretion in the collecting duct of the kidney as well as sodium and water retention.

Renin-angiotensin-aldosterone system (RAAS)

Clinical significance

Glucocorticoid synthesis

Biosynthesis of cortisol
Steps Precursor Enzyme Product
1. Pregnenolone pathway
  • 17α-hydroxylase
  • 17-hydroxypregnenolone
Progesterone pathway
2. Pregnenolone pathway
  • 17-hydroxypregnenolone
Progesterone pathway
3. Common pathway
  • 17-hydroxyprogesterone
4. Common pathway

Glucocorticoid function

See “Side effects of glucocorticoid therapy.”

To remember the effects of cortisol, think “A BIG FIB”: increased Appetite, Blood pressure, Insulin resistance, Glucose production, and decreased Fibroblasts, Immunity, and Bone formation.

Hypothalamic-pituitary gland-adrenal cortex

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

Clinical significance

Androgen synthesis [7]

Biosynthesis of androgens
Steps

Precursor

Enzyme Product
1. Pregnenolone pathway
  • 17-hydroxypregnenolone
Progesterone pathway
2. Pregnenolone pathway
  • 17-hydroxypregnenolone
  • Dehydroepiandrosterone (DHEA)
Progesterone pathway
  • Androstenedione (also synthesized in the gonads)
3. Pregnenolone pathway

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.

AnDRostenedione comes from the ADRenal glands and TESTostetone from the TESTes.

Androgen function

Adrenal androgens DHEA and androstenedione serve as precursors of:

Effects of androgens

Effects of estrogen

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

Hypothalamic-pituitary gland-adrenal cortex feedback mechanism

Clinical significance

Catecholamine synthesis

Catecholamines (norepinephrine, epinephrine, dopamine) can also be synthesized at sites in the human body other than the adrenal medulla, such as specific regions of the CNS and postganglionic adrenergic neurons.

Biosynthesis of catecholamines

Step

Precursor

Enzyme

Cofactor

Product

First hydroxylation

  • Tetrahydrobiopterin (THB)

Second hydroxylation

  • Tyrosine hydroxylase

Decarboxylation

  • DOPA decarboxylase

Hydroxylation of the β-C-Atom

  • Dopamine β-monooxygenase

Methylation

  • Phenylethanolamine-N-Methyltransferase (PNMT) (cortisol induces expression of PNMT)
  • S-Adenosylmethionine (SAM)

Epinephrine has the shortest half-life of the catecholamines.

Catecholamine function

  • Mechanism: Catecholamines bind to various adrenergic receptors (see table below) located on different organs and tissues.
  • Effects
    • Binding triggers tissue-specific responses.
    • This leads to sympathetic activation to prepare the human body for a fight-or-flight reaction.

Overview of peripheral adrenergic receptors

Receptor

G protein Signal transduction

Location

Effect

α1

  • Gq
  • ↑ Constriction of sphincters

α2

  • Gi
  • ↓ Muscular contraction

β1

  • Gs

β2

  • ↓ Contraction of smooth musculature → vasodilation and bronchodilation

β3

Regulation of secretion

  • Catecholamine secretion can be triggered by a number of stimuli, such as high-stress situations (e.g., fight-or-flight) or cortisol.

Catecholamine degradation

Clinical significance

  1. Adrenal gland & paraganglia. https://www.pathologyoutlines.com/topic/adrenalanatomy.html. Updated: July 4, 2020. Accessed: August 13, 2020.
  2. Endocrine - Adrenal Development. https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_-_Adrenal_Development. Updated: February 7, 2020. Accessed: August 13, 2020.
  3. Li Q, Johansson H, Grimelius L. Innervation of human adrenal gland and adrenal cortical lesions. Virchows Archiv. 1999; 435 (6): p.580-589. doi: 10.1007/s004280050444 . | Open in Read by QxMD
  4. McCorry LK. Physiology of the Autonomic Nervous System. Am J Pharm Educ. 2007; 71 (4): p.78. doi: 10.5688/aj710478 . | Open in Read by QxMD
  5. Wambach G. Atrial Natriuretic Peptide and the Renin-Angiotensin-Aldosterone-System. Springer Berlin Heidelberg ; 1989 : p. 53-59
  6. Oster H, Challet E, Ott V, et al. The Functional and Clinical Significance of the 24-Hour Rhythm of Circulating Glucocorticoids. Endocr Rev. 2016; 38 (1): p.3-45. doi: 10.1210/er.2015-1080 . | Open in Read by QxMD
  7. Sex Hormone Synthesis, Regulation, and Function. http://www.pathophys.org/sexhormones/. Updated: January 1, 2018. Accessed: November 21, 2018.