The reprodutive performance of PMSG-pnimed immature female rats (8 lU PMSG at 30 days of

Recently, Johnson & Witschi (1963) reported that a single injection of testosterone propionate in 5-day-old male rats (androgenization) resulted in reduced testicular and accessory organ weights at 60 days of age. In an attempt to determine the changes brought about by early post-natal androgen administration and their time of occurrence, a study was undertaken to compare the development of the gonads and accessory organs in normal and androgenized males.Rats of the Holtzman strain, maintained in air-conditioned, light-controlled quarters, fed on Wayne laboratory chow and with free access to water, were used. At 5 days of age the males were injected with either 5\m=.\0 mg. testosterone propionate in sesame oil or 0\m=.\1ml. of oil alone. At various time intervals, animals were autopsied and organ weights obtained. Tissues for histological study were fixed in Bouin's solution, embedded in paraffin, sectioned and stained with Congo red and Harris haematoxylin. Fig. 1 shows the weights (calculated as mg./100 g. body wt.) of the adrenals, hypophyses, testes and ventral prostates of androgenized males, expressed as per cent of weights obtained for normal males. At each age the number of hormone-treated (upper numerals) and normal (lower numerals) males autopsied are indicated. The controls at 60 days of age include non-injected animals used in a previous study (Johnson & Witschi, 1963).Statistical evaluation of the data reveals that the body weights were not signifi¬ cantly altered by the androgen treatment. Hypophyses, adrenals and testes did, however, show pronounced inhibitory changes. The suppression of hypophysial development is transitory and after 30 days this organ is not significantly smaller than in controls.Inhibition of the adrenals was more marked than that of the pituitary and recovery took longer. After 20 days, when the exogenous androgen had disappeared, adrenal weight began to return toward normal and was not significantly lower than that of controls at 45 or 60 days of age.The most pronounced effect of the injected androgen consists in stimulation of the accessory sex organs and depression of the testes. In controls, the testes began an active growth phase at 15 days. After the 45th day, in relation to body weight, no further testicular weight increases were seen. The ventral prostates, on the other hand, showed a slow rate of growth from the 10th to the 30th day and then remained unaltered in size for 2 weeks. At 45 days, they began a very active growth period which was nearly completed at 60 days. In androgenized males, testes did not * Present address:

Progesterone and pregn-5-ene-3,20-dione, the proposed intermediate between pregnenolone and progesterone in the rat ovary, were able to overcome the phenobarbital (PB)-induced block of ovulation in the PMSG-primed immature rats when given 3\ m=1/ 2\ hr after PB. Pregnenolone failed to cause ovulation in any of the animals treated with phenobarbital, providing support for the hypothesis that the ovulation-inhibiting action of PB may be due in part to its inhibitory action on the step in steroidogenesis between pregnenolone and progesterone. The principal metabolites of progesterone in the hypothalamus and uterus, 5\g=a\-pregnane-3,20-dione and 3\g=a\-hydroxy-5\g=a\-pregnan-20-one, were not able to overcome the PB-induced block of ovulation. These results suggest that the action of progesterone in overcoming the PBinduced block of ovulation is not because of its transformation to these two compounds.

Summary. A solution of 0-025% 20-methylcholanthrene was injected into the embryonic fluids of 10-day-old mouse embryos and the young delivered by Caesarean section at term. The incidence of the different abnormalities was found to be the same as in the groups where normal delivery was permitted. This indicates that abnormalities found in the new-born did not result from trauma during delivery.

Injection of a microquantity of 20-methylcholanthrene has been made into the fluids of 10-day-old embryos of mice of the C3H (Jax) strain. The treatment resulted in increased prenatal mortality of the embryos and many of the surviving young also showed morphological abnormalities. Examination of the young at weaning age revealed certain deformities and pathological conditions. The relation of some of the abnormalities to naturally occurring mutations is significant. An additional observation was the occurrence of similar abnormalities in the litters born after the treated litter.Since the abnormalities in the present study resemble the ones observed in a similar investigation conducted earlier, as well as the ones caused by irradiation and other teratogenic agents, it is proposed that the mode of action of the carcinogen might also be the same.