HORMONES, ADRENAL-CORTICAL

Since the introduction of cortisone (1) (1948) and hydrocortisone (2) (1951), adrenal-cortical hormones have remained an important and unreplaced dmg class. Though not without adverse effects, these compounds have continued to be the dmg of choice in the treatment of afflictions ranging from the moderate skin rash to severe acute inflammatory disorders, and are included in many other therapeutic regimes. 

Adrenal Cortical Hormones" under "Hormones" in ECT 1st ed., VoL 7, pp. 495—513, by H. B. MacPhUlamy, Ciba Pharmaceutical Products and T. F. Gallagher, Sloan-Kettering Institute for Cancer Research "Steroids with Cortical Hormone Activity" in ECT 1st SuppL, pp. 849—888, by G. Aimer and A. Wettstein, Ciba Limited, Basle "Adrenal-Cortical Hormones" under "Hormones" in ECT 2nd ed., Vol. 11, pp. 77—93, by W. R. Ebedein, The Children s Hospital of Philadelphia in ECT 3rd ed., Vol 12, pp. 575—602, by V. Petrow, Consultant. 

Corticosteroids are hormones secreted from the adrenal cortex. These hormones arise from the cortex of the adrenal gland and are made from the crystalline steroid alcohol cholesterol. Synthetic forms of the natural adrenal cortical hormones are available The potent antiinflammatory action of the corticosteroids makes these drugs useful in the treatment of many types of musculoskeletal disorders. The corticosteroids are discussed in Chapter 50. 

Mitotane, or o,p -DDD, is an oral medication used in the treatment of adrenocortical carcinoma. Chemically it is an isomere of DDT. Following its metabolism in the adrenal cortex to a reactive acyl chloride intermediate, mitotane covalently binds to adrenal proteins, specitically inhibiting adrenal cortical hormone production. The drug accumulates in fat tissue. It is eliminated mainly by the kidneys with a half-life of 18-159 days. Common side effects include anorexia, nausea, lethargy, sleepiness and skin problems. 

In the animal body three important groups of hormones are formed by the metabolism of cholesterol the progestins, the sex hormones, and the adrenal cortical hormones 249 Their synthesis occurs principally in mitochondria of the adrenal cortex and the gonads. Steroid hormone synthesis is regulated by hormones, such as corticotropin (ACTH), from the anterior pituitary250 (see Chapter 30) and is also dependent upon the recently discovered steroidogenic acute regulatory protein, which in some way promotes the movement of stored cholesterol into mitochondrial membranes.251 252 Some major pathways of... 

There are relationships between the adrenal cortical hormones and the thyroid and pituitary glands. Depression or the function of the adrenals produces thyroid deficiency, w hereas administration of thyroxine stimulates the ACTH-adrenal conical mechanism. 

The major metabolic transformations of the adrenal-cortical hormones generally follow the metabolism of cortisol, which undergoes the following conversions in vitro ... 

Anabolic effects Anabolic steroids can be used to treat senile osteoporosis and severe burns, to speed recovery from surgery or from chronic debilitating diseases, and to counteract the catabolic effects of externally administered adrenal cortical hormones. 

Steroids include sex hormones and adrenal cortical hormones cortisone is one), cardiac glycosides, and bile acids. Because of their biological importance— and, undoubtedly, because of the fascinating complexity of the chemistry—the study of steroids has been, and is now, one of the most active areas of organic chemical research. 

A -cortisol prednisolone, cortisone (ban. inn] (cortisone acetate [usan] Kendall s compound E Reichstein s Substance Fa Wintersteiner s compound F NSC 9703 Cortisyl ) is a natural adrenal cortical hormone, a CORTICOSTEROID, which is converted to hydrocortisone in the liver. It has both GLUCOCORTICOID and MINERALOCORTICOID activity. It can therefore be used orally to make up for hormonal deficiency (especially mineral balance), for instance, following surgical removal of the adrenal glands. It can also be used for its ANTIINFLAMMATORY and ANTIALLERGIC properties in treating rheumatoid arthritis and in rheumatic fever therapy, cortisone acetate cortisone. 

Adrenal cortical hormones are controlled by the hypothalamus, which secretes corticotropin-releasing hormone (CRH) in response to stress situations. CRH, then, causes the anterior pituitary gland to release corticotropin into the circulation. Adrenal cortical surface receptors are then stimulated by corticotropin to produce and release the corticoid steroids. 

Adrenal cortical hormones readily pass through the cell membranes of target tissue into the cytosol, where they interact with and bind to specific intracellular receptor proteins. It appears that there are high-affinity cytoplasmic receptors for the various physiologic steroids. 

The biosynthesis and secretion of these adrenal cortical hormones are influenced by the hypothalamus-pituitary axis and the adrenocorticotrophic hormone (ACTH) and its associated feedback mechanisms (Figure 10.3.1). The secretions of ACTH are pulsatile, and they are influenced more by the central nervous system and the pituitary gland than the glucocorticoid feedback mechanisms. 

The circulating levels of adrenal cortical hormones in rats depend on several factors, including age, season, and strain (Wong et al. 1983 Carnes et al. 1994), gender... 

The steroid hormones, derived from cholesterol, include the adrenal cortical hormones (e.g., cortisol, aldosterone, and the adrenal sex steroids dehy-droepiandrosterone [DHEA] and androstenedione) and the gonadal hormones (e.g., the ovarian and testicular sex steroids, such as testosterone and estrogen). 

---