Retardation of first ovulation in pubertal rats after treatment with 5 alpha-androstane-3 alpha, 17 beta-diol or its 3 beta-epimer.

The effect was studied of five daily injections of 50 microgram of either 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-androstanediol) or its 3 beta-epimer (3 beta-androstanediol), starting on day 22 of life, on sexual maturation in female rats. No difference was found in the age and body weight at first oestrus between oil-treated rats and rats treated with either 3 alpha- or 3 beta-androstanediol. The only difference observed between these groups consisted of the occurrence of a "pinhole" vaginal opening a few days before oestrus in 50% of the steroid-treated rats; in oil-treated rats immediate full vaginal opening and first oestrus coincided in ten out of 12 rats. Different effects were obtained when the higher dose of 100 microgram daily was used; effects were dissimilar in rats treated with 3 alpha- and 3 beta-androstanediol. If administration of the higher dose of 3 beta-androstanediol was started on day 22 and continued until the day of full vaginal opening and first oestrus, a significant delay of this first oestrus, preceded by a few days of a "pinhole" type of vaginal opening was observed. After administration of the higher dose of 3 alpha-androstanediol a "pinhole" type of vaginal opening, accompanied by dioestrous-like vaginal smears, was also found, but oestrus did not occur during the period when injections were given. After the injections were stopped on day 45, first oestrus developed within 6 days in all rats. The previous findings of others that administration of 3 beta-androstanediol to the immature female rat may induce precocious puberty (i.e. precocious vaginal opening and first ovulation) were not confirmed in the present study. Out results indicate that high doses of free 3 alpha-androstanediol, and to a lesser degree 3 beta-androstanediol, may even delay first ovulation in the rat. A possible interference of 3 alpha-androstanediol with the triggering of the first ovulatory gonadotrophin peaks is discussed.