THE ADRENAL CORTEX

Background information

The adrenals are paired glands that lie above the kidneys. They have an inner medulla and an outer cortex. The medulla can be considered to be a sympathetic ganglion: it secretes catecholamines, epinephrine and norepinephrine. The cortex secretes several steroid hormones distinguished in three categories,
* glucocorticoids, e.g. cortisol in humans, corticosterone, in rats
* sex hormones, e.g., dehydroepiandrosterone (DHEA). Cortisol and DHEA are secreted by the cells of the zona fasciculata and zona reticularis, and corticosterone is secreted by these and also the zona granulosa
* minerolocorticoids, e.g., aldosterone, are secreted by the cells of the zona glomerulosa.

A. GLUCORTICOIDS AND SEX HORMONES

Glucorticoids have several actions. The major metabolic actions of glucocorticoids include:
* increased amino acid uptake and gluconeogenesis in liver,
* decreased amino acid uptake and protein synthesis in muscle,
* inhibition of somatic growth due to a general catabolic (decreased protein synthesis) action,
* suppression of pituitary growth hormone secretion,
* anti-insulin effect with consequent exacerbation of diabetes, and
* mobilization of serum lipids and cholesterol.

Glucocorticoids have anti-inflammatory activity. When administered in supra-physiologic doses, they inhibit inflammatory and allergic reactions. These immunosuppressive actions, utilized clinically for the prevention of transplant rejections and the symptomatic treatment of allergies, have been explained by several mechanisms (e.g. inhibition of leucocyte migration from blood to tissues, decreased number of circulating lymphocytes and reduced antibody production).

Glucocorticoids have also effects on the nervous system, primarily of an excitatory nature, evidenced by the presence of hormone receptors on neurons and glia, induction of neurotransmitter enzymes, EEG changes and increased convulsibility, toxicity for specific neurons.

Another important action of glucocorticoids is their negative feedback on hypothalamus and pituitary. They inhibit the secretion of adrenocorticotropic hormone (ACTH) from the pituitary and of corticotropin-releasing hormone (CRH) from the hypothalamus: the higher the levels of the circulating hormones, the lower the secretion of ACTH and CRH; the lower their levels, the greater the ACTH and CRC release.

Other actions of glucocorticoids include: retention of sodium at renal tubules (but much less efficacious than aldosterone), the reabsorption of bone and altered calcium metabolism, promotion of appetite and increased stomach acid and pepsin secretion, maintenance of work capacity.

Sex hormones include both androgens such as dehydroepiandrosterone (DHEA) (with masculinizing and anabolic actions) and estrogens (with feminizing actions). Their secretion decreases markedly in old age.

B. MINERALOCORTICOIDS

Aldosterone, the major mineralocorticoid, is indispensable for survival. It increases sodium reabsorption from the renal tubular fluid, saliva and gastric juice. In the kidney, aldosterone acts on the epithelium of the distal tubule and collecting duct where it facilitates the exchange of sodium (reabsorbed) for potassium and hydrogen ions (excreted). It may also increase potassium and decrease sodium in muscle and brain cells.

Secondary actions include: maintenance of blood pressure (as a consequence of sodium-water retention and increased blood volume); moderate potassium diuresis and increased urine acidity (sodium taken up is exchanged for potassium and hydrogen ions which are excreted).

THE ADRENAL MEDULLA

The medullary cells (also known as chromaffin cells) are considered to be postganglionic neurons (innervated by preganglionic cholinergic fibers) which have lost their axons and become secretory cells. Major secretory products are the catecholamines, norepinephrine, which also is produced and released by neurons in the CNS and by sympathetic neurons, epinephrine, formed primarily in the medulla by the methylation of norepinephrine, and some dopamine, also a CNS neurotransmitter. Opioid peptides are also secreted (most of the circulating encephalin comes from the medulla) although they do not pass the blood-brain barrier.

Norepinephrine and epinephrine mimic the effects of sympathetic discharge, stimulate the nervous system and exert metabolic effects that include glycogenolysis in liver and skeletal muscle, mobilization of free fatty acids and stimulation of metabolic rate. They act through the binding to two classes of receptors, alpha(1 and 2)receptors,which induce vasoconstriction in most organs and beta receptors which mediate the metabolic effects and stimulate rate and force of cardiac contraction (ß1) and dilate blood vessels in muscle and liver (ß2). Their secretion is under neural control and is also influenced by other hormones, primarily glucocorticoids and thyroid hormones