STUDIES ON THE METABOLISM OF CORTICOSTEROIDS IN THE HUMAN FOETO-PLACENTAL UNIT

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Abstract
A mixture of deoxycorticosterone-1,2-3H (21-hydroxy-4-pregnene-3,20-dione) and corticosterone-4-14C (11β,21-dihydroxy-4-pregnene-3,20-dione) was injected in two cases at laparotomy into the intact foeto-placental circulation 15 minutes prior to the interruption of gestation. Metabolites present in the placenta and various foetal tissues were separated and isolated in a radiochemically homogeneous form. In the two experiments, 58 and 86 per cent, respectively, of the administered radioactive material was recovered from the placenta plus foetal tissues; only 2 and 4 per cent, respectively, was recovered from the urine. The only compound possessing both 3H and 14C label was corticosterone isolated from the adrenals. The following 3H-labelled metabolites were isolated: 3α,21-dihydroxy-5β-pregnan-20-one (liver, intestines, residual foetal tissues), 20β,21-dihydroxy-4-pregnen-3-one (placenta and residual foetal tissues), 3β,21-dihydroxy-5α-pregnan-20-one (liver), 3,20-dioxo-4-pregnen-21-yl-sulphate (liver, intestines, lungs, kidneys, adrenals and residual foetal tissues). The following 14C-labelled metabolites were isolated: 21-hydroxy-4-pregnene-3,11,20-trione (placenta, liver, lungs, kidneys, residual foetal tissues), 3α,11β,21-trihydroxy-5β-pregnan-20-one (liver, intestines, residual foetal tissues), 11β-hydroxy-4-pregnene-3,20-dion-21-yl-sulphate (liver, intestines, lungs, kidneys, adrenals and residual foetal tissues). The results indicate that the foetal adrenals convert a part of the circulating deoxycorticosterone to corticosterone. It is concluded that the reductive metabolism of deoxycorticosterone in the liver of the midgestation foetus differs qualitatively and quantitatively from that of corticosterone. A concept is presented describing the metabolism of deoxycorticosterone and corticosterone in the foeto-placental unit at midgestation.

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