Abstract
It has been suggested that in the rat, 5α-androstane-3α, 17β-diol (3α-diol) is physiologically involved in restraining the onset of female puberty. To test this hypothesis several experiments were performed. In normal rats, serum levels of 3α-diol decline slightly during the initial phases of puberty and then sharply several hours before the afternoon preovulatory LH surge on the day of first proestrus. Inhibition of 5α-reductase activity with a highly specific inhibitor, 17β-N, N-diethylcarbamoyl-4-methyl-4-aza-5α-androstane-3-one (4-MA) strikingly depressed both ovarian content and serum levels of 3α-diol, but failed to advance vaginal opening or first ovulation. Administration of different doses of 3α-diol to juvenile rats via Silastic capsules produced a dose-related increase in serum 3α-diol levels. Titers attained ranged from values similar to those of untreated juvenile rats to levels more than 10-fold higher. None of the concentrations, however, inhibited the LH surge and ovulation induced by pregnant mare serum gonadotropin (PMSG). When a similar treatment was administered to normally maturing rats, only the high dose of 3α-diol delayed the age of vaginal opening and of first ovulation. Serum 3α-diol levels attained with this dose were markedly higher than those of untreated juvenile rats (1,086 ± 267 vs. 124 ± 14 pg/ml, respectively). The results indicate that high serum levels of 3α-diol have the capacity to delay the onset of female puberty, but that the prepubertal decrease in serum 3α-diol levels which occurs under normal physiological conditions does not play a significant role in determining the time of puberty. It also appears that juvenile type levels of 3α-diol do not exert a major feedback effect on prepubertal gonadotropin release, and thus they do not represent an important restraining influence on the occurrence of puberty.