The Sex Steroids

The carbonyl group at position 20 (12-3) was reduced by means of amalgamated zinc to give the pregnane nucleus 

Treatment of dehydroepiandrosterone (13-3) with phosphorus pentachloride replaces the hydroxyl at position 3 with retention of configuration (13-4). It had been established prior to this work that catalytic reduction of unsaturation in steroids proceeds almost invariably from the bottom side to afford reaction products as their 5a epimers, as for example 

13-5 [this is also the case for cholestanol (13-1), obtained from hydrogenation of cholesterol]. Sodium acetate then displaces chlorine in 13-5 to afford the acetoxy derivative 13-6 with inverted configuration at C3. Mild hydrolysis of the acetoxy group affords the corresponding alcohol 13-2 that is identical with that of a sample produced by oxidation of cholestanol (13-1). 

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The sex steroids comprise a class of hormones, including estrogens, progestins, and androgens, which play important roles in the development and maintenance of... 

E. Casali, P. H. Petra, and J. B. A. Ross, Fluorescence investigation of the sex steroid binding protein of rabbit semm Steroid and subunit dissociation, Biochemistry 29, 9334-9343 (1990). 

It has long been established that the sexual status of an animal controls and coordinates its growth rate and speed of fattening. Bulls grow faster and lay down more lean meat in the carcass than steers, whereas steers grow faster with a higher feed conversion efficiency than cows. These beneficial effects on animal performance are due to the sex steroids produced in the testes. 

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... 

The sexes are known to react differently to opiates. In humans, women are more likely to misuse opiates. Research in animals shows that females require higher doses to relieve pain (the sex steroid hormones change the brain s organization early in life to create this difference). Female rats also appear to enjoy morphine more than males. The females continued to choose to receive the drug even at doses so high that their breathing was halted, doses that the males chose to avoid. 

The superfamily of regulatory proteins that interacts with hormones such as cortisol, the sex steroids estradiol and testosterone, thyroxine and with... 

Whether unoccupied GR are totally nuclear is less clear. Immunocytochemical studies with anti-GR antibodies show both cytoplasmic and nuclear localization at the light level, and an increase in nuclear staining simultaneous with decreased cytoplasmic staining in response to addition of glucocorticoids [106-109]. It may well be that GR have a different intracellular distribution from the sex-steroid receptors. 

The Sex Steroid Pathway Is Initiated by 17a-Hydroxylase/17,20-Lyase (CYP17)... 

The valve that allows entry of 17-OH pregnenolone into the sex steroid pathway is the 17,20-lyase component of CYP17, the SER enzyme that catalyzes the 17a-hydroxylation of steroids. As noted above, the lyase component of the enzyme is active in certain tissues for reasons that are not currently clear. Both A" and steroids are known to feed into the sex steroid pathways although the absence of 3/6HSD precludes the former. It should be emphasized that the formation of androgenic steroids is necessary before estrogen formation is possible therefore, the initial reaction in the sex steroid pathway invariably produces an androgenic steroid. 

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