Comparison of human fetal hepatic and adrenal cytochrome P450 activities with some major gestational steroids and ethylmorphine as substrates

Abstract

The immunoidentified human fetal liver and adrenal microsomal contents of cytochromes P450IIIA and P450VIIA1 were compared to the metabolism of steroids and ethylmorphine. In fetal liver microsomes, 16α-hydroxylation of dehydroepiandrosterone (DHA) was catalyzed at a high rate in almost all investigated specimens and accompanied by a high ethylmorphine N-demethylase activity. Progesterone 16α- and 17α-hydroxylation was found only in the livers with the highest DHA 16α-hydroxylation activities, while 21-hydroxylation of progesterone was catalyzed only occasionally in these samples. In fetal adrenal microsomes, 21-hydroxylation of progesterone to 11-desoxycorticosterone (DOC) and 11-desoxycortisol (DOCOL) was catalyzed. In contrast to fetal liver, the adrenals also catalyzed the 17α-hydroxylation of pregnenolone and the formation of DHA from 17α-OH-pregnenolone. 16α-hydroxylation of DHA and ethylmorphine N-demethylation were modest in the adrenals. P450IIIA/HLp was immunoidentified in all investigated liver specimens except two ( 18 20 ) in which no ethylmorphine N-demethylation or 16α-hydroxylation of DHA was found. P450XVIIA1 bands were observed in 8 20 blots of liver specimens, but there was no correlation between the density of these bands and the 17α-hydroxylation of progesterone. All 11 fetal adrenal samples catalyzed DHA 16α-hydroxylation, although only 8 were positive for P450IIIA/HLp. All investigated adrenals were positive in regard of the P450XVIIA1 band, except one ( 8 9 ) with a low 17α-hydroxylation of progesterone. All adrenal specimens catalyzed 21-hydroxylation of progesterone and contained P450C21 bands in immunoblots and all samples catalyzed the formation of DOC and DOCOL from progesterone. Our findings in the fetal livers show a correlation between the DHA 16α-hydroxylation and immunoidentified P450IIIA/HLp bands. In adrenals, there was a correlation between the immunoidentified P450XVIIIA1 bands and the 17α-hydroxylation of progesterone.