Adrenocortical Steroid 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. 

Adrenocortical hormone (Section 27.6) A steroid hormone secreted by the adrenal glands. There are two types of adrenocortical hormones mineralocorticoids and glucocorticoids. 

Cholesterol is probably the best known steroid because of its association with atherosclerosis. However, biochemically it is also of significance because it is the precursor of a large number of equally important steroids that include the bile acids, adrenocortical hormones, sex hormones, D vitamins, cardiac glycosides, sitosterols of the plant kingdom, and some alkaloids. 

Schimmer, B.P. and Parker, K.L., Adrenocorticotropic hormone adrenocortical steroids and their synthetic analogs inhibitors of the synthesis and actions of adrenocortical hormones, in Goodman and Gilman s The Pharmacological Basis of Therapeutics, 9th ed., Hardman, J.G. and Limbird, L.E., Eds., McGraw-Hill, New York, 1996, chap. 59. 

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. 

The remaining steroid lipids constitute two main classes of steroid hormones sex hormones and adrenocortical hormones. The sex hormones include androgens (testosterone, androsterone), estrogens (estrone, estradiol), and progestins (progesterone). The adrenocortical hormones include mineralocorticoids (aldosterone) and glucocorticoids (hydrocortisone). 

However, broadly steroids can be classified only in to two main classes sex or reproductive hormones and adrenocorticoid or adrenocortical hormones. 

The natural adrenocortical hormones are steroid molecules produced and released by the adrenal cortex. Both natural and synthetic corticosteroids are used for the diagnosis and treatment of disorders of adrenal function. They are also used—more often and in much larger doses—for treatment of a variety of inflammatory and immunologic disorders. 

We first describe the biosynthesis of fatty acids, the primary components of both triacylglycerols and phospholipids, then examine the assembly of fatty acids into triacylglycerols and the simpler membrane phospholipids. Finally, we consider the synthesis of cholesterol, a component of some membranes and the precursor of steroids such as the bile acids, sex hormones, and adrenocortical hormones. 

Steroid Hormones The steroid hormones (adrenocortical hormones and sex hormones) are synthesized from cholesterol in several endocrine tissues. 

Schimmer BP, Parker KL. Adrenocorticotropic hormone adrenocortical steroids and their synthetic analogs inhibitors of the synthesis and actions of adrenocortical hormones. In Brunton LL, et al, eds. 

Some of the most important physiological steroids are the adrenocortical hormones, synthesized by the adrenal cortex. Most of these hormones have either a carbonyl group or a hydroxyl group at Cl 1 of the steroid skeleton. The principal adrenocortical hormone is cortisol, used for the treatment of inflammatory diseases of the skin (psoriasis), the joints (rheumatoid arthritis), and the lungs (asthma). Figure 25-10 compares the structure of natural cortisol with two synthetic corticoids fluocinolone acetonide, a fluori-nated synthetic hormone that is more potent than cortisol for treating skin inflammation and beclomethasone, a chlorinated synthetic hormone that is more potent than cortisol for treating asthma. 

Schimmer BP, Parker KL (1995) Adrenocorticotropic Hormone Adrenocortical Steroids and Their Synthetic Analogs Inhibitors of the Synthesis and Actions of Adrenocortical Hormones. In Hardman JG, Limbird LE (eds) Goodman Gilman s The Pharmacological Basis of Therapeutics, 9th Edition. McGraw-Hill, New York, pp 1459-1485 Sullivan AT, Kinter LB (1995) Status of safety pharmacology in the pharmaceutical industry 1995. Drug Dev Res 35 166-172... 

Suitable derivatives to render most steroids more stable and volatile for gas chromatography and to improve their mass spectrometric properties have been developed. The trimethylsilyl ethers [206] or the methoxime-trimethylsilyl ethers of hydroxy keto steroids [207] have been widely used and their mass spectra extensively studied [204], A comparison of the GC-MS behaviour of several derivatives of some of the adrenocortical hormones has been made [208], including methoxime-trimethylsilyl ethers, dimethylsiliconides, methyl boronates, oxetanones and acetonides. The recently described improved preparation of enol-trimethylsilyl ethers of corticoids [209] should also prove of value. 

Anabolic steroids do not usefully counter the unwanted catabolic effects of the adrenocortical hormones. 

The fact that most of the Holarrhena alkaloids are characterized by substitution in position 18 was utilized for preparation of a series of nitrogen-free, 18-substituted steroids, which are of interest in relation to the adrenocortical hormone aldosterone. A detailed description would be beyond the scope of this summary. However, since some steps in these syntheses constitute interesting reactions of Holarrhena alkaloids, a brief outline, dealing with the principles of these procedures, will be presented here. 

In 1952 workers at the Upjohn Company discovered an efficient one-step 1 la-hydrox-ylation by the use of the mold Rhizopus arrhizuz. This reaction became crucial in the commercial production of various adrenocortical hormones and thereby synthetic analogs as well. Large-scale synthesis of other steroidal drugs have also become possible by the discovery of other organisms capable of highly (stereo) specific transformations. Table 14-2... 

The evidence in favour of a relationship between non-steroidal antirheumatic activity and the pituitary-adrenal system is based mainly on experiments involving salicylates and phenylbutazone. No attempt will be made to discuss these problems in detail since they have been adequately reviewed by Smith and Done for salicylates, and by Rechenburg for phenylbutazone. Smith argued persuasively that the available experimental evidence on salicylates does not support the view that they either mimic or reinforce the actions of the natural adrenocortical hormones, and that the similar clinical effects of salicylates and these steroids in rheumatic diseases must therefore be produced by different mechanisms. Done, on the other hand, suggests that the concept cannot be prematurely dismissed and believes that the possibility that salicylate simultaneously affects the production and disposition of adrenocortical hormones deserves further consideration. He emphasizes that the antirheumatic effects of salicylates are not dependent on the maintenance of elevated circulating levels of corticoids. 

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