Adrenal cortex Totally Explained

Everything about Adrenal Cortex totally explained

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 organisation. A useful mnemonic, GFR, relates to the glomerular filtration rate, as used in clinical practice.

Layer	Name	Primary product
Most superficial cortical layer	zona glomerulosa	mineralocorticoids (eg, aldosterone)
Middle cortical layer	zona fasciculata	glucocorticoids (eg, cortisol)
Deepest cortical layer	zona reticularis	weak androgens (eg, dehydroepiandrosterone)

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's 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're 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.

Pathology

Adrenal insufficiency (for example due to Addison's disease)

Cushing's syndrome

Congenital adrenal hyperplasia

Conn's syndromeFurther Information

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