The metabolism of 7- 3H-pregnenolone and 4- 14C-progesterone by adrenal homogenates of fetal guinea-pigs and other mammalian fetuses

Abstract

Adrenal tissue homogenates from fetal guinea-pigs were incubated with 7- 3H-pregnenolone or 4- 14C-progesterone and analyzed for conversion products by reverse isotope dilution procedures. Cortisol and 11β-hydroxyandrostenedione were synthesized from both substrates; corticosterone was formed only from progesterone. The results indicated a similarity in the metabolism of pregnenolone and progesterone by adrenal cortical tissue of late gestation guinea-pig fetuses with that of adult guinea-pigs. The isolation of 11β-hydroxy-androstenedione demonstrates C 19 steroid synthesis by fetal adrenal tissue in a species other than the human, and suggested two pathways of pregnenolone metabolism in this tissue. Fetal armadillo and rat adrenals converted pregnenolone or progesterone to corticosterone or cortisol; canine adrenal preparations showed limited metabolic activity. Steroid synthesis in the adrenal cortex of the human fetus is characterized by the production of 3β-hydroxy-5-steroids including the C 19 steroid, dehydroepiandrosterone-sulfate 3, and by an inhibition of corticosteroid synthesis (1, 2). In contrast, cortisol or corticosterone are the major products of adrenal steroidogenesis in fetal rats (3), armadillos (4), and sheep (5). 3β-Hydroxy-5-steroids or androgenic C 19 steroids have not been reported as products of adrenal steroidogenesis in these species. Price and Ortiz reported that adrenal glands of fetal guinea-pigs maintained in organ culture together with fragments of rat prostatic tissue prevented regression of these fragments (6). They further found 3β-hydroxy-5-steroid dehydrogenase activity in the adrenal glands, leading to the conclusion that the capacity for secreting steroidal androgens existed in the adrenal cortex of fetal guinea-pigs (7). The observations of Price and Ortiz prompted the experiments reported here, i.e., in vitro incubations of fetal guinea-pig adrenals with labeled pregnenolone or progesterone. In addition, evidence was sought for 3β-hydroxy-5 -steroid and C 19 steroid formation in adrenals of fetal rats, armadillos and dogs.