Abstract
Metabolism of progesterone in ovaries of prepubertal rats has been investigated by incubating intact ovaries from immature rats in Krebs-Ringer bicarbonate buffer containing 10−6 M progesterone-4-[14C] and isolating the radioactive metabolites formed after varying periods of incubation. Androsterone was the most abundant metabolite produced by ovaries from 28–30-day-old rats. Luteinizing hormone (LH) injected 0.5–4 h before autopsy, or added directly to incubation media, resulted in markedly decreased formation of androsterone with a concomitant proportional increase in production of 3α-OH-5α-pregnane-20-one (3α-OH-5α-P). Production of other androgens (androstenedione, testosterone, 5α-androstane-3α,17β-diol), which accumulated in smaller amounts than androsterone, was also inhibited by LH. Prolactin administration for 6 days before autopsy resulted in only minor alterations of progesterone metabolism, causing small increases in accumulation of 5α-pregnane-3,20-dione (5α-P) and 3α-OH-5α-P in the absence of LH and slightly enhancing the inhibitory effects of LH on formation of androstenedione and androsterone. Ovaries from 23-day-old rats produced significantly more androsterone and less androstenedione than did those from 29-day-old rats in the absence of exogenous hormone treatment. When follicular growth was induced and first estrus synchronized by administration of 4 IU pregnant mare serum gonadotropin (PMSG) to 28-day-old rats at 0800 h (Day 0), androsterone production from progesterone-4-[14C] gradually increased, reaching maximum levels at 2200 h on Day 1 and remained elevated until 1400 h on Day 2 (the equivalent of proestrus). With the first detectable rise in serum LH levels on Day 2, androsterone production declined abruptly, reaching minimum levels at 2200 h on Day 2. Production of 3α-OH-5α-P, a relatively minor metabolite before the LH surge, increased markedly and became the major metabolite at 1800 and 2200 h, coincident with the LH surge. These results are consistent with a regulatory role for 5α-reduced gonadal steroids in the ovarian maturation processes during the peripubertal period and indicate an ability of LH, both exogenous and endogenous, to alter markedly the ratio of C19/C21, steroids by an inhibitory action on the 17α-hydroxylase-C17,20-lyase step.
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