The »early-androgen« syndrome in the rat – i. e. anovulatory ovaries in adult females after a single injection of testosterone propionate (TP) within a week of birth – may not become apparent until some time after the attainment of sexual maturity. Large doses (50 or 100 μg) of TP were effective earlier than lower doses (5 or 10 μg). Rats which received 5 μg TP were ovulating at 10 weeks of age, mated but were infertile at 13 weeks of age, and were anovulatory at 21 weeks. In rats between 10 and 13 weeks old there was a marked fall in the number of corpora lutea in the ovaries of animals which had been given 5 μg TP. Hemi-spaying was followed by compensatory growth of the remaining ovary which consisted of corpora lutea in ovulating, and of follicles in anovulatory rats; little or no compensatory weight increase occurred in animals which seemed to be in the transition stage from the ovulatory to the anovulatory condition.

SUMMARY A single s.c. injection of 0·5 mg. testosterone propionate to rats aged 2 or 5 days affected development and subsequent activity of the reproductive tract, and somatic growth. As adults, females displayed prolonged vaginal oestrus with lack of ovulation and with uteri smaller than in control-injected animals likewise killed when in oestrus; males had smaller testes, seminal vesicles and ventral prostates. Body growth increased in treated females and decreased in males. Data on specific gravity and weights of heart, liver and kidneys, indicate that both the normal sex difference and the changes in weight due to early androgen administration are attributable to overall differences in size and not to specific differences in any particular body component. These effects of the steroid appear to be comparable to those noted after castration at an early age.

The interaction between dose and time of administration of testosterone propionate (TP) on the development of sexual function was studied by giving a single dose of 5, 10, 50 or 500 μg TP to young rats of both sexes on the day of birth (day 1) or on day 2, 4 or 5. The effectiveness of androgen administration before birth was studied by giving a single injection of 2500 μg TP to pregnant rats on day 19 to 22 after conception. Pre-natal administration had no effect on the function of the ovaries of female offspring, although the dose was sufficient to cause masculinization of the external genitalia. The weight of the testes and accessories of the male offspring were not affected. The effects of post-natal TP administration on ovarian function varied with the dose and with the time of administration. Threshold doses (5 and 10 μg) were more effective the earlier they were given after birth. With these small doses, most of the rats had normal luteinized ovaries at 10 weeks and were able to bear and suckle normal litters. Some time later ovulations ceased so that at 21 weeks they were no longer fertile; at 27 weeks there were no more corpora lutea in the ovaries. In males, a dose of 50 μg of TP or more resulted in permanently reduced weight of testes, seminal vesicles and prostate. The earlier the treatment, the more marked was the depression of weight. From these results and others reported in the literature the following deductions can be made: (1) the critical period of brain sensitivity to physiological amounts of androgen probably lies between days 4 and 6 (day of birth counted as day 1); (2) a rough estimate of the amount of androgen secreted by the newborn male rat during the critical period would seem to be the equivalent of a single injection of 5–50 μg TP; (3) after the physiological critical period has elapsed a female rat can still be »masculinized« if a high dose of TP is given, up to a period of between 10–20 days after birth.

In the present study it was found that doses of 10 and 25 mg testosterone propionate (TP) given to pregnant rats could induce the early-androgen syndrome. These doses caused delayed parturition with intra-uterine death and inhibition of lactation with early post-natal death of the young; these events could be avoided by Caesarian section and foster mothers. In other experiments TP was injected directly into the foetuses or their amniotic sacs. A dose of 20 μg into the amniotic sac was without effect on subsequent ovarian activity and, with one exception, on the external genitalia of the young. Injection of 20 or 100 μg into the foetus caused both external masculinization and anovulatory ovaries. The apparent low sensitivity of the foetus to TP injected into the pregnant doe seems to be due to poor transmission of the steroid from the maternal into the foetal body. The foetal external genitalia appear to be more sensitive to TP than the mechanism which sets the future gonadotrophic pattern of the brain-pituitary complex.

No abstract