Tissues metabolism, adrenocortical hormones

In humans, most steroids function as hormones, chemical messengers that are secreted by endocrine glands and carried through the bloodstream to target tissues. There are two main classes of steroid hormones the sex hormones, which control maturation, tissue growth, and reproduction, and the adrenocortical hormones, which regulate a variety of metabolic processes. 

Deficient animals have an impaired ability to respond to metabolic and physical stress as a result of this decreased adrenocortical hormone synthesis, although this may be accompanied by enhanced sensitivity of target tissues to hormone action. Some strains of rat are susceptible to the development of duodenal ulcers in pantothenic acid deficiency. Ulceration can be prevented by adrenalectomy and is exacerbated by administration of glucocorticoid hormones. 

Among the most abundant steroids, cholesterol is present in almost all human and animal tissue (Real Life 4-2). Bile acids are produced in the liver as part of a fluid delivered to the duodenum to aid in the emulsification, digestion, and absorption of fats. An example is cholic acid. Cortisone, used extensively in the treatment of rheumatoid inflammations, is one of the adrenocortical hormones produced by the outer part (cortex) of the adrenal glands. These hormones participate in regulating the electrolyte and water balance in the body, as well as in protein and carbohydrate metabolism. 

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. 

Experiments of this type are subject to several intrinsic difficulties which Winters discusses in some detail. Adrenal function can be assayed by physiological responses of this type only if the tissue on which the adrenal hormone acts is functioning normally. Owing to the critical role of coenzyme A in intermediary metabolism, the maintenance of normal function in any tissue during severe pantothenate deficiency is doubtful. However, experiments attempting to define adrenocortical function by studies of carbohydrate metabolism in situations of severe pantothenate deficiency are partially justified by the finding of Olson and Kaplan (1948) that in the rat the adrenal cortex suffers an earlier depletion of coenzyme A than does the liver. After 3 weeks of pantothenate deficiency, coenzyme A was significantly decreased in the adrenal and heart, whereas it was still at normal levels in the liver and kidney. After 6 weeks on the... 

---