Adrenal cortex mineralocorticoids

It was known for some time that even after the corticoids had been separated from crude extracts of the adrenal cortex, the remaining material, the so-called "amorphous fraction" still possessed considerable mineralocorticoid activity. Aldosterone (250), one of the last steroids to be isolated from this fraction, proved to be the active principle. This compound proved to be an extremely potent agent for the retention of salt, and thus water, in body fluids. An antagonist would be expected to act as a diuretic in those edematous states caused by excess sodium retention. Although aldosterone has been prepared by both total and partial synthesis, the complexity of the molecule discouraged attempts to prepare antagonists based directly on the parent compound. 

The adrenal gland lies on the superior surface of each kidney. It is a double organ composed of an outer cortex and an inner medulla In response to ACTH secreted by the anterior pituitary, the adrenal cortex secretes several hormones (the glucocorticoids, the mineralocorticoids, and small amounts of sex hormones). 

This section of the chapter discusses the hormones produced by the adrenal cortex or the adrenocortical hormones, which are the glucocorticoids and mineralocorticoids. These hormones are essential to life and influence many organs and structures of the body. The glucocorticoids and mineralocorticoids are collectively called corticosteroids. 

Cortisol synthesis requires three hydroxylases located in the fasciculata and reticularis zones of the adrenal cortex that act sequentially on the Cjy, C21, and Cjj positions. The first two reactions are rapid, while Cu hydroxylation is relatively slow. If the C, position is hydroxylated first, the action of 17a-hydroxylase is impeded and the mineralocorticoid pathway is followed (forming corti-... 

The steroid hormones known as mineralocorticoids and glucocorticoids are synthesized in the adrenal cortex of mammals [3]. The physiological mineralocorticoid is... 

Adrenal cortex Glucocorticoids Mineralocorticoids Sex hormones Steroids... 

Angiotensin II has two effects first, as a vasoconstrictor acting via receptors on vascular smooth muscle cells, and second, it stimulates the adrenal cortex gland to produce aldosterone (a mineralocorticoid steroid hormone, see Chapter 4). Aldosterone promotes the reabsorption of sodium from the renal tubule into the bloodstream and the resulting increase in osmolality (osmotic potential) of the blood causes water reabsorption in the nephrons. The outcome is an increase in blood volume and, therefore, pressure which inhibits (by negative feedback) further renin secretion from the JGA. 

Glucocorticoids and mineralocorticoids are uniquely produced by the adrenal cortex, and are collectively termed corticosteroids. Apart from aldosterone, glucocorticoid secretion is regulated by the pituitary hormone, corticotrophin. The principal corticosteroids synthesized in the body are illustrated in Figure 1.6. Glucocorticoids generally exhibit weak mineralocorticoid actions and vice versa. 

The steroidal nature of adrenocortical hormones was established in 1937, when Reichstein synthesized desoxycorticosterone. Eventually it was clearly established that the adrenal cortex elaborated a number of hormones and that these compounds differed in their amount of inherent metabolic (glucocorticoid) and electrolyte regulating (mineralocorticoid) activity. The actions of these hormones extend to almost every cell in the body. In humans, hydrocortisone (cortisol) is the main carbohydrate-regulating steroid, and aldosterone is the main electrolyte-regulating steroid. 

Another major function of the adrenal cortex is the regulation of water and electrolyte metabolism. The principal mineralocorticoid, aldosterone, can increase the rate of sodium reabsorption and potassium excretion severalfold. This will occur physiologically in response to sodium or volume depletion or both. The primary site of... 

Corticosterone. A natural corticoid with moderate glucocorticoid activity and some mineralocorticoid activity, possessing life-maintaining properties in adrenalectomized animals and several other activities peculiar to the adrenal cortex. Its actions closely resemble those of cortisol, except that it is not anti-inflammatory. 

ACTH stimulates the adrenal cortex to secrete glucocorticoids, mineralocorticoids and... 

AdrenocorticotrophicAnterior Stimulates adrenal cortex to secrete hormone (ACTH) pituitary glucocorticoids, mineralocorticoids, and Melanocyte- androgens stimulates melanocytes ... 

Adrenocorticotropin (ACTH) Corticotropin-releasing hormone (CRH)(+) Adrenal cortex Glucocorticoids, mineralocorticoids, androgens... 

The adrenocorticotrophic hormone ACTH (corticotropin) stimulates the adrenal cortex to secrete the glucocorticoids hydrocortisone (cortisol) and corticosterone, the mineralocorticoid aldosterone, and a number of weakly androgenic substances, as well as a small amount of testosterone. Aldosterone synthesis is also regulated by renin and angiotensin. 

Adrenal cortex Glucocorticoids Mineralocorticoids Regulate glucose metabolism enhance response to stress Regulate fluid and electrolyte levels... 

Mineralocorticoids are involved in controlling electtolyte and fluid levels.9,44 The primary mineralo-corticoid produced by the adrenal cortex is aldosterone. Aldosterone increases the reabsorption of sodium from the renal tubules. By increasing sodium reabsorption, aldosterone facilitates the reabsorption of water. Aldosterone also inhibits the renal reabsorption of potassium, thus increasing potassium excretion. Mineralocorticoid release is regulated by fluid and electrolyte levels in the body and by other hormones, such as the renin-angiotensin system. 

This chapter discusses the pharmacology of the steroid hormones that are produced by the adrenal cortex. The two primary types of adrenal steroids are the glucocorticoids and mineralocorticoids. Small amounts of other steroids such as the sex hormones (androgens, estrogens, and progestins) are also produced by the adrenal cortex. These steroids are discussed in Chapter 30. 

Mineralocorticoids are also steroid hormones that are produced by the adrenal cortex. The principal mineralocorticoid in humans is aldosterone. Aldosterone is primarily involved in maintaining fluid and electrolyte balance in the body. This hormone works on the kidneys to increase sodium and water reabsorption and potassium excretion. 

Drugs with mineralocorticoidlike activity (aldosterone agonists) are frequently administered as replacement therapy whenever the natural production of mineralo-corticoids is impaired. Mineralocorticoid replacement is usually required in patients with chronic adrenocortical insufficiency (Addison disease), following adrenalectomy, and in other forms of adrenal cortex hypofunction. These conditions usually require both mineralocorticoid and glucocorticoid replacement. 

The two principal groups of adrenal steroids are the glucocorticoids and mineralocorticoids. These hormones are synthesized from cholesterol within cells of the adrenal cortex. The primary glucocorticoid produced in humans is cortisol (hydrocortisone), and the primary mineralocorticoid is aldosterone. Glucocorticoids exert a number of effects such as regulation of glucose metabolism, attenuation of the inflammatory response, and suppression of the immune system. Mineralocorticoids are involved primarily in the control of fluid and electrolyte balance. 

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