HUMAN FOETAL ADRENAL 4-ENE-3-OXOSTEROID SYNTHESIS: AN INVESTIGATION OF [4-14C]PREGNENOLONE AND [4-14C]-DEHYDROEPIANDROSTERONE METABOLISM USING NEW TECHNIQUES

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Abstract
SUMMARY: Human foetal adrenal slices were incubated with [4-14C]pregnenolone (20 foetuses) and [4-14C]dehydroepiandrosterone (18 foetuses). Product 4-ene-3-oxosteroids were isolated as a group and measured in toto by a double isotope dilution procedure. Production of compounds of the 4-ene-3-oxosteroid fraction was estimated over several time-intervals and relative to the protein content of the incubated tissue. No conversion of [4-14C]pregnenolone by foetal adrenal tissue to 4-ene-3-oxosteroids was detectable although metabolism of the substrate to other compounds was indicated. Conversion of [4-14C]dehydroepiandrosterone to 4-ene-3-oxosteroids, principally androstenedione, occurred in incubations of tissue from 7 of the 10 male foetuses studied with this substrate, and from 2 of undetermined sex, but not from 6 female foetuses so studied. Testosterone formation from [4-14C]dehydroepiandrosterone was not detectable. There was no apparent variation in 4-ene-3-oxosteroid formation relative to foetal age in the range investigated (approximately 6–20 foetal weeks). These results are interpreted, in the light of previous studies, as giving credence to the concept of substrate specificity in human foetal adrenal 4-ene-3-oxosteroid formation. The evidence that foetal adrenal androstenedione formation may be sex-dependent is considered, and the implications discussed.

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