Hormones of the Adrenal Cortex

Hormones of the Adrenal Cortex
The mammalian adrenal gland is a double gland composed of two unrelated types of glandular tissue: an outer region of adrenocortical cells, or cortex, and an inner region of specialized cells, the medulla (Figure 36-13). In nonmammalian vertebrates homologs of adrenocortical and medullary cells are organized quite differently; they may be intermixed or distinct, but never arranged in a cortex-medulla relationship as in mammals.

At least 30 different compounds have been isolated from adrenocortical tissue, all of them closely related lipoidal compounds known as steroids. Only a few of these compounds are true steroid hormones; most are various intermediates in the synthesis of steroid hormones from cholesterol (Figure 36-14). Corticosteroid hormones are commonly classified into two groups, according to their function: glucocorticoids and mineralocorticoids.

Glucocorticoids, such as cortisol (see Figure 36-14) and corticosterone, are concerned with food metabolism, inflammation, and stress. They promote synthesis of glucose from compounds other than carbohydrates, particularly amino acids and fats. The overall effect of this process, called gluconeogenesis, is to increase the level of glucose in the blood, thus providing a quick energy source for muscle and nervous tissue. Glucocorticoids are also important in diminishing the immune response to various inflammatory conditions. Because several diseases of humans are inflammatory diseases (for example, allergies, hypersensitivity, and rheumatoid arthritis), these corticosteroids have important medical applications.

Figure 36-13 Paired adrenal glands of humans, showing gross structure and position on the upper poles of the kidneys. Steroid hormones are produced by the cortex. The sympathetic hormones epinephrine and norepinephrine are produced by the medulla.

The adrenal steroid hormones, especially the glucocorticoids, are remarkably effective in relieving symptoms of rheumatoid arthritis, allergies, and various disorders of connective tissue, skin, and blood. Following the report in 1948 by P. S. Hench and his colleagues at the Mayo Clinic that cortisone dramatically relieved the pain and crippling effects of advanced arthritis, the steroid hormones were hailed by the media as “wonder drugs.” Optimism was soon dimmed, however, when it became apparent that severe side effects always attended long-term administration of antiinflammatory steroids. Steroid therapy lulls the adrenal cortex into inactivity and may permanently impair the body’s capacity to produce its own steroids. Today steroid therapy is applied with caution, because it is realized that the inflammatory response is a necessary part of the body’s defenses.

Synthesis and secretion of glucocorticoids are controlled principally by ACTH of the anterior pituitary (see Figure 36-6), while ACTH is controlled by corticotropin-releasing hormone (CRH) of the hypothalamus (Table 36-1). As with pituitary control of the thyroid, a negative feedback relationship exists between CRH, ACTH, and the adrenal cortex (Figure 36-3). An increase in release of glucocorticoids suppresses output of CRH and ACTH; the resulting decline in blood level of CRH and ACTH then feeds back to the adrenal cortex to inhibit further release of glucocorticoids. An opposite sequence of events happens should the blood level of glucocorticoids drop: CRH and ACTH output increases which in turn stimulates secretion of glucocorticoids. CRH is known to mediate stressful stimuli through the adrenal axis.

Figure 36-14 Hormones of the adrenal cortex. Cortisol (a glucocorticoid) and aldosterone (a mineralocorticoid) are two of several steroid hormones synthesized from cholesterol in the adrenal cortex.

Mineralocorticoids, the second group of corticosteroids, are those that regulate salt balance. Aldosterone (see Figure 36-14) is by far the most important steroid of this group. Aldosterone promotes tubular reabsorption of sodium and tubular secretion of potassium by the kidneys. Since sodium usually is in short supply in diets of many animals and potassium is in excess, the mineralocorticoids play vital roles in preserving the correct balance of blood electrolytes. The salt-regulating action of aldosterone is controlled by the renin-angiotensin system, described on and by blood levels of potassium ions. High levels of potassium ions in the blood are a potent direct stimulator of aldosterone release from the adrenal cortex, thus promoting reabsorption of sodium into the blood and secretion of excess potassium ions into the urine.

The adrenocortical tissue also produces androgens (Gr. andros, man, + genesis, origin), which, as the name implies, are similar in effect to the male sex hormone, testosterone. Adrenal androgens promote some developmental changes that occur just before puberty in human males and females. Recent development of so-called anabolic steroids, synthetic hormones related to testosterone, has led to widespread abuse of steroids among athletes (see following note).

Use of anabolic steroids by athletes became major news following Ben Johnson’s drugfueled win of the 100-meter race at the 1988 Olympics. Despite almost universal condemnation by Olympic, medical, and college sports authorities, an unscientific and clandestine program of experimentation with anabolic steroids has become popular with many amateur and professional athletes in many countries.These synthetics (and testosterone and its precursors) cause hypertrophy of skeletal muscle and may improve performance that depends on strength. Unfortunately, they also have serious side effects, including testicular atrophy (and infertility), periods of irritability, abnormal liver function, and cardiovascular disease. In 1990, a National Institute of Drug Abuse survey reported that nearly 3% of high school seniors (5% of males and 0.5% of females) had used steroids at some time in their lives. More recent surveys suggest that steroid use among high school males has been stable since 1991, but use in high school females has shown a significant increase since then. Yesalis, C.E., C.K Barsukiewicz, A.N.Kopstein, and M.S. Bahrke. 1997. Trends in anabolic-androgenic steroid use among adolescents. Arch. Pediatr. Adolesc. Med. 151 (2):1197-1206). Use among adults and professional athletes is not well documented, although anecdotal evidence suggests that such drugs are popular among athletes in a variety of sports (the most famous recent athlete being Mark McGwire of the St. Louis Cardinals).