Adrenal cortex

Overview
Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.

Layers
The cortex can be divided into three distinct layers of tissue based on their organization.

Steps of hormone synthesis

 * All adrenocortical hormones are synthesised from cholesterol.


 * Cholesterol is transported into the inner mitochondrial membrane by steroidogenic acute regulatory protein, where it is converted into pregnenolone by the enzyme . Accordingly, production of hormones in all three layers of the adrenal cortex is limited by the transportation of cholesterol into the mitochondria and by its conversion into pregnenolone.


 * Pregnenolone can be either dehydrogenated to progesterone, or hydroxylated to 17-alpha-hydroxypregnenolone.

The steps up to this point occur in many steroid-producing tissues. Subsequent steps, however, only occur in the adrenal cortex:
 * Progesterone -> (hydroxylation at C21)-> Deoxycorticosterone ->(two further hydroxylations)-> Aldosterone
 * Progesterone -> (hydroxylation at C17)-> 17-alpha-hydroxyprogesterone ->(hydroxylation)-> Deoxycortisol ->(hydroxylation)-> Cortisol

Production
The adrenal cortex produces a number of different corticosteroid hormones:
 * Mineralocorticoids: They are produced in the zona glomerulosa. The primary mineralocorticoid is aldosterone. Its secretion is regulated by the oligopeptide angiotensin II (angiotensin II is regulated by angiotensin I, which in turn is regulated by renin). Aldosterone is secreted in response to high extracellular potassium levels, low extracellular sodium levels, and low fluid levels and blood volume. Aldosterone affects metabolism in different ways:
 * It increases urinary excretion of potassium ions
 * It increases interstitial levels of sodium ions
 * It increases water retention and blood volume


 * Glucocorticoids: They are produced in the zona fasciculata. The primary glucocorticoid released by the adrenal gland is cortisol. Its secretion is regulated by the hormone ACTH from the anterior pituitary. Upon binding to its target, cortisol enhances metabolism in several ways:
 * It stimulates the release of amino acids from the body
 * It stimulates lipolysis, the breakdown of fat
 * It stimulates gluconeogenesis, the production of glucose from newly-released amino acids and lipids
 * It increases blood glucose levels in response to stress, by inhibiting glucose uptake into muscle and fat cells
 * It strengthens cardiac muscle contractions
 * It increases water retention
 * It has anti-inflammatory and anti-allergic effects


 * Androgens: They are produced in the zona reticularis. The most important androgens include:
 * Testosterone: a hormone with a wide variety of effects, ranging from enhancing muscle mass and stimulation of cell growth to the development of the secondary sex characteristics.
 * Dihydrotestosterone (DHT): a metabolite of testosterone, and a more potent androgen than testosterone in that it binds more strongly to androgen receptors.
 * Androstenedione (Andro): an androgenic steroid produced by the testes, adrenal cortex, and ovaries. While androstenediones are converted metabolically to testosterone and other androgens, they are also the parent structure of estrone.
 * Dehydroepiandrosterone (DHEA): a steroid hormone produced from cholesterol. It is the primary precursor of natural estrogens. DHEA is also called dehydroisoandrosterone or dehydroandrosterone.

Mnemonics
The layers of the cortex can be remembered with the mnemonic GFR: G - glomerulosa, F - fasciculata, R - reticularis.

Another mnemonic that is used is Go Find Rex, Make Good Sex: G - glomerulosa, F - fasciculata, R - reticularis, M - mineralcorticoids, G - glucocorticoids, S - sex hormones. (This mnemonic simplifies the relationship between the locations of production of glucocorticoids and sex hormones.)

Another mnemonic is "Salt, Sugar, Sex: The deeper you go, the sweeter it gets."  As one moves layers into the adrenal cortex, compounds that control salt (mineralcorticoids), sugar (glucocorticoids), and sex (weak androgens) are produced.

Pathology

 * Adrenal insufficiency (e.g. due to Addison's disease)
 * Cushing's syndrome
 * Congenital adrenal hyperplasia
 * Conn's syndrome