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The appearance of intermediates and products in the transformation of 4-androstene-3,17-dione and testosterone to estrone and 17β-estradiol by human placental microsomes was studied. The variables investigated were time, temperature and the concentrations of reduced pyridine nucleotides and of testosterone. The relative amounts of metabolites were markedly influenced by all of the factors studied except temperature, although the reaction velocity at 37 °C was about twice that at 27 °C. Oxidoreduction at C-17 in starting material, intermediates and products was examined using a mixture of [4-14C]testosterone and [7β,17α-²H2]testosterone as substrate. Oxidation and reduction at C-17 was most prominent at the beginning and the end of the reaction sequence. 17α-Hydroxy-5α-androst-1-en-3-one was found to be an inhibitor of the C19 17β-hydroxysteroid dehydrogenase activity of human placental microsomes. [ABSTRACT FROM AUTHOR]

Biosynthesis and site of formation of epitestosterone in the human foetus was investigated by incubation of androstenedione with subcellular fractious of mid-gestational foetal liver. Testesterone and epitestosterone were purified by thin-layer chromatography and resolved by gas-liquid chromatography. Epitestosterone (and testosterone) were identified by gas chromatography-mass spectrometry as silyl ether and methoximesilyl ether derivatives. The ratio testosterone : epitestosterone found in the incubations was about 20:1. Both 17β- and 17α-hydroxysteroid oxidoreductase activities were found in the 105000×g microsome fraction as well as in the cytosol fraction. It may be concluded that the human foetal liver is one of the sources of production of epitestosterone, and that androstenedione is one of its precursors. The possibility that androstenedione and epitestosterone are precursors of maternal urinary 17α-hydroxyphenolic steroids during pregnancy is discussed. [ABSTRACT FROM AUTHOR]

The metabolism of testosterone in human foetal adrenal glands at mid-gestation was investigated in vitro. After incubations with microsome preparations in a medium supplemented with NADPH-regenerating system, the metabolites were isolated by thin-layer and gas-liquid chromatography, and identified by gas chromatography-mass spectrometry. 4-Androstenedione, 3β-hydroxy-4-androsten-17-one and 4-androstene-3α (and 3β),17β-diols were identified in both incubation series. The presence of 1β-, 2α-, 2β-, 6α- and 6β-hydroxylase activities in foetal adrenal glands was demonstrated by the isolation of the corresponding testosterone derivatives. The biosynthesis of these steroids in human adrenal gland has not been demonstrated before. Because 3β-hydroxy-4-androsten-17-one and epimeric 4-androstene-3α (and 3β),17β-diols could be isolated in these incubation studies the presence of 3α, 3β- and 17β-hydroxysteroid oxidoreductase in the adrenal gland preparation is very likely. Neither 5α(H)- nor 5β(H)-ring reductase activities have been detected. [ABSTRACT FROM AUTHOR]