C(19)-5-ene steroids in nature

Dehydroepiandrosterone (DHEA), produced from cholesterol in the adrenals, is the most abundant steroid in our circulation. It is present almost entirely as the sulfate ester, but the free steroid is the form that serves as a precursor of estrogens and androgens, as well as 7- and 16-oxygenated derivatives. Mammalian tissues reduce the 17-keto Group of DHEA to produce androstenediol-a weak estrogen and full-fledged androgen. Its androgen activity is not inhibited by the anti-androgens commonly used to treat prostate cancer. It is probably responsible for the growth of therapy-resistant prostate cancer. DHEA is hydroxylated at the 7 alpha position, and this derivative is oxidized by 11 beta-hydroxysteroid dehydrogenase to form 7-keto DHEA. The latter is reduced by the same dehydrogenase to form 7 beta-hydroxy DHEA. When fed to rats, each of the latter three steroids induce the formation of two thermogenic enzymes in the liver. The late-term human fetus produces relatively large amounts of 16 alphahydroxy DHEA, which serves the mother as a precursor of estriol.