Layers of cortex.
The adrenal cortex
|Latin||cortex glandulae suprarenalis|
Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, such as aldosterone and cortisol, respectively. It is also a secondary site of androgen synthesis. Recent data suggest that adrenocortical cells under pathological as well as under physiological conditions show neuroendocrine properties; within the normal adrenal, this neuroendocrine differentiation seems to be restricted to cells of the zona glomerulosa and might be important for an autocrine regulation of adrenocortical function.
The adrenal cortex comprises three main zones, or layers. This anatomic zonation can be appreciated at the microscopic level, where each zone can be recognized and distinguished from one another based on structural and anatomic characteristics. The adrenal cortex exhibits functional zonation as well: by virtue of the characteristic enzymes present in each zone, the zones produce and secrete distinct hormones.
- Zona glomerulosa
- The outermost layer, the zona glomerulosa is the main site for production of aldosterone, a mineralocorticoid, by the action of the enzyme aldosterone synthase (also known as CYP11B2). Aldosterone is largely responsible for the long-term regulation of blood pressure. Aldosterone's effects are on the distal convoluted tubule and collecting duct of the kidney where it causes increased reabsorption of sodium and increased excretion of both potassium (by principal cells) and hydrogen ions (by intercalated cells of the collecting duct). Sodium retention is also a response of the distal colon, and sweat glands to aldosterone receptor stimulation. Although sustained production of aldosterone requires persistent calcium entry through low-voltage activated Ca2+ channels, isolated zona glomerulosa cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit Ca2+ channels entry. However, mouse zona glomerulosa cells within adrenal slices spontaneously generate membrane potential oscillations of low periodicity; this innate electrical excitability of zona glomerulosa cells provides a platform for the production of a recurrent Ca2+ channels signal that can be controlled by angiotensin II and extracellular potassium, the 2 major regulators of aldosterone production. Angiotensin II originates from plasmatic angiotensin I after the conversion of angiotensinogen by renin produced by the juxtaglomerular cells of the kidney.
- The expression of neuron-specific proteins in the zona glomerulosa cells of human adrenocortical tissues has been predicted and reported by several authors and it was suggested that the expression of proteins like the neuronal cell adhesion molecule (NCAM) in the cells of the zona glomerulosa reflects the regenerative feature of these cells, which would lose NCAM immunoreactivity after moving to the zona fasciculata. However, together with other data on neuroendocrine properties of zona glomerulosa cells, NCAM expression may reflect a neuroendocrine differentiation of these cells.
- Zona fasciculata
- Situated between the glomerulosa and reticularis, the zona fasciculata is responsible for producing glucocorticoids, such as 11-deoxycorticosterone, corticosterone, and cortisol in humans. Cortisol is the main glucocorticoid under normal conditions and its actions include mobilization of fats, proteins, and carbohydrates, but it does not increase under starvation conditions. Additionally, cortisol enhances the activity of other hormones including glucagon and catecholamines. The zona fasciculata secretes a basal level of cortisol but can also produce bursts of the hormone in response to adrenocorticotropic hormone (ACTH) from the anterior pituitary.
- Zona reticularis
- The inner most cortical layer, the zona reticularis produces androgens, mainly dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and androstenedione (the precursor to testosterone) in humans.
All adrenocortical steroid hormones are synthesized from cholesterol. Cholesterol is transported into the adrenal gland. The steps up to this point occur in many steroid-producing tissues. Subsequent steps to generate aldosterone and cortisol, however, primarily occur in the adrenal cortex:
- Progesterone → (hydroxylation at C21) → 11-Deoxycorticosterone → (two further hydroxylations at C11 and C18) → Aldosterone
- Progesterone → (hydroxylation at C17) → 17-alpha-hydroxyprogesterone → (hydroxylation at C21) → 11-Deoxycortisol → (hydroxylation at C11) → Cortisol
The upper (multi-colored) adrenocortical steroid pathway illustration at right has an error. It is not aromatase which converts estrone to estradiol, it is 17-hydroxysteroid dehydrogenase (see adjacent, parallel, orange pathway) which converts estrone to estradiol. If somebody knows how to get this fixed, please do so.
The primary mineralocorticoid, aldosterone, is produced in the adrenocortical zona glomerulosa by the action of the enzyme aldosterone synthase (also known as CYP11B2). Aldosterone is largely responsible for the long-term regulation of blood pressure. Aldosterone effects on the distal convoluted tubule and collecting duct of the kidney where it causes increased reabsorption of sodium and increased excretion of both potassium (by principal cells) and hydrogen ions (by intercalated cells of the collecting duct). Sodium retention is also a response of the distal colon, and sweat glands to aldosterone receptor stimulation. Although sustained production of aldosterone requires persistent calcium entry through low-voltage activated Ca2+ channels, isolated zona glomerulosa cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit Ca2+ channels entry. However, mouse zona glomerulosa cells within adrenal slices spontaneously generate membrane potential oscillations of low periodicity; this innate electrical excitability of zona glomerulosa cells provides a platform for the production of a recurrent Ca2+ channels signal that can be controlled by angiotensin II and extracellular potassium, the 2 major regulators of aldosterone production. Angiotensin II originates from plasmatic angiotensin I after the conversion of angiotensinogen by renin produced by the juxtaglomerular cells of the kidney.
They are produced in the zona fasciculata. The primary glucocorticoid released by the adrenal gland is cortisol in humans and corticosterone in many other animals. 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
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): It is the primary precursor of natural estrogens. DHEA is also called dehydroisoandrosterone or dehydroandrosterone. The reticularis also produces DHEA-sulfate due to the actions of a sulfotransferase, SULT2A1.
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