A decrease in uptake of tritiated testosterone by the hypothalamus was observed in adult, castrated male rats previously injected with 100 μg oestradiol undecylate on either postnatal days 1 or 5. Moreover, a decrease in pituitary incorporation of labelled testosterone was observed in those animals injected with oestradiol on day 1. Neonatal (5 day) male rats injected with oestradiol 3 hours prior to administering labelled testosterone showed a significant decrease in uptake of label in the pituitary and an increase in uptake by the hypothalamus as compared to oil injected controls. It is suggested that neonatal oestrogenization of male rats affects testosterone receptor mechanisms in the hypothalamus and/or pituitary.

Male mice were injected on the fifth postnatal day with 50 pg of estradiol undecylate and the changes in morphology and testis cholesterol were studied at 10, 20, 40, 60 and 90 days. Such treatment resulted in decreased body weight, atrophic testes and seminal vesicles, adrenal and pituitary hypertrophy, failure of scrota1 development with cryptorchidism, impaired spermatogenesis, and alopecia. The onset of these changes, however, occurred at different ages. Testicular atrophy was manifest as early as day 20, while seminal vesicle atrophy and adrenal hypertrs phy were not apparent until day 40, and a decreased body weight and alopecia were observed by day 60. Pituitary hypertrophy was observed at only day 90. There were no significant differences in total testicular cholesterol between estrogenized and control mice at ten days. However, at all other stages studied experimental animals had significantly more cholesterol than their oil injected controls. This increase in cholesterol within the testes of estrogenized mice is interpreted as decreased utilization of cholesterol for steroidogenesis. That there was a lack of endogenous androgen in these estrogenized mice as late as 90 days was indicated by atrophic seminal vesicles and the presence of an x-zone in the adrenal gland.Most of the studies concerning the effects of neonatal hormone administration on reproductive function have employed female rats and mice (see review by Saun--ders, '68). Recently, neonatal injection of male rats (Kincl et al., 63; Arai, '64; Harris and Levine, '65; Schiavi, '68) and mice (Simmons, '64; Mori, '67) with estrogen has been shown to cause serious and seemingly permanent malfunctions in their reproductive systems. Adult male rats and mice injected neonatally with estrogen are sterile, have atrophic testes with impaired spermatogenesis, and atrophic accessories. These studies have, for the most part, analyzed only one or two postpuberal age groups, with little attention to the prepuberal male. The purpose of the present study is two-fold. First, to examine the morphological changes which occur progressively after treating male mice with estrogen on day 5. Second, we have undertaken a study of the progressive changes which occur in testicular cholesterol in normal and estrogenized mice since there have been no studies concerning biochemical properties of the testes of these estrogenized animals. MATERIALS AND METHODSMale mice of the Swiss albino strain, bred in the Bureau of Biological Research, Rutgers University, or in our laboratory in Oxford, were used in these studies. On the third postnatal day litters were reduced to six males, and on the fifth day three members of the litter were injected subcutaneously with 0.1 ml of sesame oil containing 50 vg of estradiolundecylate (Delestrec, Squibb). The remaining three animals were injected with 0.1 ml of sesame oil and served as controls. All animals were housed in animal quarters with regulated lighting (14 hours light -10 hours dark) and were fed Purina laboratory chow an...

Neonatal female rats treated with testosterone (12.5 μg/day) from days 4–8, or with a single injection of 62.5 μg of testosterone propionate on day 5, exhibit the persistent oestrus-anovulatory syndrome. The simultaneous injection of 6 μg reserpine/day (days 4–8) or a single injection of 30 μg of reserpine failed to alter the effect of testosterone propionate. Neonatal administration of reserpine alone, whether in multiple or single injections of the same aforementioned dosages, exerted no deleterious effect on the oestrus cycles of female rats. However, the ovaries of reserpine treated animals were heavily luteinized.

The uptake of radioactivity in the adrenal glands of 5-day-old male and female rats was examined 2 h following injection of radiolabeled testosterone, R1881, diethylstilbestrol, or estradiol. The adrenals of both sexes had higher levels of radioactivity than blood after testosterone or synthetic androgen (R1881) injection. The adrenals of neither sex showed any significant accumulation of radioactivity, following ³H-estradiol injection. When, however, cytosol prepared from neonatal adrenal glands was incubated with 2 nM ³H-estradiol, and the incubate subjected to column chromatography on Sephadex G-100, radioactivity was eluted with the void volume; this peak was absent with the addition of 100-fold unlabeled estradiol to the incubation. The possible role of α-fetoprotein in preventing the in vivo uptake and retention of 17β-estradiol is discussed since ³H-diethylstilbestrol, an estrogen which has low affinity for this protein, was retained by the adrenals of male rats. It is concluded that estrogens or androgens can have a direct effect on the neonatal adrenal gland.