Metabolism of dehydroepiandrosterone and dehydroepiandrosterone sulphate by the human foetus at midpregnancy.

Abstract

ABSTRACT Four previable foetuses (18th to 20th week of gestation) were perfused with a combination of 14C-labelled dehydroepiandrosterone (DHA) and 3H-labelled dehydroepiandrosterone sulphate (DHAS). Approximately 80% of the radioactive material administered was recovered from the various foetal tissues and perfusates. With the exception of the liver, which exhibited an approximately equal concentration of the two isotopes, all foetal tissues contained more 14C-than 3H-labelled material. On an average, 27% of the 14C-, and 8% of the 3H-labelled material administered was retained by the foetal organism. Approximately 80% of the 14C-labelled material recovered from the foetal tissues was in a conjugated form; very little, if any of the 3H-labelled material was recovered as unconjugated (free) material. More than 90% of the conjugated radioactive material present in the different foetal tissues, except the liver and residual foetus, was isolated and identified as DHAS. The 3H- to 14C-ratio of the DHAS isolated from various tissues showed marked differences; it was lowest in the lungs and adrenals, indicating that these organs are active sites of sulpho-conjugation of DHA. In addition to DHAS, androst-5-ene-3β,17β-diol 3-sulphate (Δ5-DIOLS) and androst-5-ene-3β,16α,17β-triol 3-sulphate (Δ5-TRIOLS) were isolated from the liver and a smaller amount of Δ5-TRIOLS from the residual foetal tissues. From the perfusates, 3β,16α-dihydroxyandrost-5-en-17-one 3 sulphate (16αHO-DHAS) was isolated. The 3H- to 14C-ratio of the Δ5-TRIOLS isolated from the liver was considerably lower than those of Δ5-DIOLS and DHAS isolated from the same organ. It is concluded that DHA is extensively sulphurylated by a variety of foetal tissues, very little, if any DHAS is hydrolysed by the foetal organism, DHAS and also some DHA is 16α-hydroxylated by the previable foetus, the foetal liver is the principal site of 16α-hydroxylation of the DHAS circulating in the foeto-placental unit.