Ontogeny of mitochondrial steroidogenesis in the guinea pig gonad

To determine whether steroidogenesis in the developing guinea pig may be limited by the formation of pregnenolone, cholesterol side chain cleavage activity was ascertained at various stages of development. The conversion of 1,2-³H]cholesterol to 1,2-³H]pregnenolone was detected in mitochondria isolated from fetal guinea pig ovaries and testes as early as day 35 of gestation, while no metabolism was noted in day 30 animals. Moreover, no l,2-³H]progesterone was formed during the 60 minute incubation. From day 35 of gestation to the day of birth, the percentage of pregnenolone formed per testis (total activity) increased, while total activity in the ovary declined. In contrast, gonadal mitochondria from adult guinea pigs converted cholesterol to both pregnenolone and progesterone and total activity in these animals was substantially higher than in their fetal counterparts. In the three females examined, the rate of pregnenolone and progesterone synthesis varied according to the stage of the estrous cycle during which these animals were sacrificed. Conversion of pregnenolone to progesterone was most rapid in the early luteal phase animal, while conversion of cholesterol to pregnenolone occurred more rapidly in the periovulatory animals than in ovarian mitochondria from the late luteal phase of the cycle. The results indicate that during prenatal and postnatal development of the gonad, cholesterol side chain cleavage activity changes and that mitochondria may acquire a Δ⁵-3β-hydroxysteroid dehydrogenase.