Metabolism of Progesterone by the Perfused Adrenalectomized Human Fetus1

Abstract

Three male 2 female previahle human fetuses (18th to 22nd week of gestation) were totally adrenalectomized perfused with progesterone-4-C14 . The following metabolites were isolated and identified in the fetal tissues and perfusate: 17[alpha]-hydroxyprogesterone from the residual fetal tissues; 6[beta]-hydroxyproges-terone from lung and perfusate; pregnanediol from perfusate and liver; pregnanolone from perfusate, liver and intestine; 3[beta]-hydroxy-5[alpha]-pregnan-20-one from lung, kidney and residual tissues; and 20[alpha]-dihydroprogesterone from all tissues analyzed. Androstenedione was not found in any of the tissues examined, while progesterone was recovered from all of them. A high degree of enzymic stereo -specificity in the reduction of progesterone to 3[alpha],5[beta]- and 3[beta],5[alpha]-epimeric pregnanolone was observed in the various fetal tissues. This specificity was identical with that found following the perfusion of intact fetuses with progesterone-4-C14. In the absence of adrenals the midterm previable human fetus can, under the conditions used in these experiments, metabolize progesterone to a large number of products and the liver is a major site of this metabolism. Tissues other than the adrenals can hydroxylate progesterone at C-6 and C-17 but not at C-11 and C-21. The extra-adrenal formation of 17[alpha]-hydroxypro-gesterone and Its possible role in fetal testicular androgen synthesis is discussed.