Changes in pathways of steroid production taking place in the rat ovary around the time of the first ovulation

Abstract

The metabolism of progesterone in the rat ovary approaching the first ovulation, induced by pregnant mare serum gonadotrophin (PMS)-administration, was examined. In the untreated immature rat, progesterone is metabolized mainly through 5α-reduced pregnanes. 5α-androstane-3α,17β-diol (3α-A) being the main metabolite. Following the first ovulation, 20α-hydroxypregn-4-en-3-one (20α-OHP), and to a lesser extent, 5α-pregnane-3α,20α-diol (allo-P) are the main products. The temporal concentration of 3α-A and of its 3β epimer in peripheral blood of immature rats was measured by RIA. It appears, that in vivo, too. the level of the androstanediols decline before the first ovulation. In order to study this shift in steroid production, the pathways by which the main metabolites are produced were examined several hours before the first ovulation. For this. double labelling and trapping experiments. as well as kinetic studies were performed. The results obtained show that four possible pathways by which 3α-A and allo-P can be formed, co-exist for a short time in the ovary approaching the first ovulation. These results indicate that 5α-reductase. the enzyme responsible for ring A reduction. has a key position in the shift from the “immature” to the “mature” type of steroid metabolism. A considerable decline in 5α-reductase activity was found following administration of PMS: 1 day after the stimulation, a 40% decrease in activity was measured. On the 3rd day. one-tenth of the original activity was detected and by the 7th day only residual activity remained. The collective data obtained in this study explains the shift in steroidogenesis taking place in the ovary at the time of the first ovulation. The importance of these findings to the mechanism of the onset of puberty is discussed.