Steroid biosynthesis pharmacological effects

Steroid hormones bear a remarkable structural similarity to one another (see Fig. 29-1). The precursor for steroid biosynthesis is cholesterol. Consequently, all of the steroid hormones share the same basic chemical configuration as their parent compound. This fact has several important physiologic and pharmacologic implications. First, even relatively minor changes in the side chains of the parent compound create steroids with dramatically different physiologic effects. For instance, the addition of only one hydrogen atom in the sex steroid pathway changes testosterone (the primary male hormone) to estradiol... 

In the safety pharmacology protocol, the interaction of multiple endocrine systems in test animals is addressed. As discussed by Harvey (1996) and by Harvey and Everett (2003), effects on adrenocortical function are frequently found in toxicology studies, sometimes related to enzyme induction and effects on steroid biosynthesis (Loose et al. 1983, Nebert and Russell 2002, Weber et al. 1993). Test procedures in animals are required when there is a reason for concern. Frequently however the effects observed are due to stress rather than specific interaction with the target organ, and may involve effects on catecholamine release from the adrenal medulla (Tucker 1996). Recently, much new evidence has been accumulated from the testing of industrial chemicals with effects on adrenal steroid biosynthesis (Harvey and Johnson 2002). 

The corticosteroids exert their pharmacological effect by modifying RNA and protein synthesis in target tissue. After binding to the specific cytoplasmic protein receptors, the steroid-receptor complex is transported to the nucleus, where it binds to the nuclear chromatin, thereby altering the transcription of RNA. Since the steroids are not stored, the steroid concentration in the plasma is maintained by regulation of steroid biosynthesis. 

Steroid structure and biosynthesis have been used from a pharmacologic standpoint. Pharmacologists have tried to develop more effective and less toxic synthetic steroids by manipulating the chemical side groups of these compounds. An example is the synthetic glucocorticoid dexamethasone, which is 25 times... 

---