Gonadal Activity and Sexual Differentiation of the Hypothalamus

The administration of testosterone propionate (TP) or estradiol benzoate (EB) to the neonatal female rat induces masculinization of the hypothalamus and results in a tonic pattern of gonadotropin (GTH) secretion and the absence of ovulation. To determine the relation between this effect of steroids on the developing hypothalamus and endogenous gonadal activity, newborn rats were subjected to gonadectomy and/or steroid injection, or gonadal transplantation. The mode of GTH secretion of the host was ascertained by examining the histology of subcutaneous ovarian grafts. Corpora lutea (CL) in such grafts were considered as evidence of the cyclic release of GTH, and their absence as evidence of the tonic or masculine mode of GTH secretion. CL were found in ovarian grafts removed from females ovariectomized on day 2 or 6 of age, and from males castrated on day 2 or 3, some of which received ovarian grafts at the time of castration. CL were absent in grafts removed either from neonatally ovariectomized females given testicular grafts or a single injection of microgram dosages of sex steroids, or from males castrated after 3 days of age. The female pattern of GTH secretion, which is established following castration of the 2-day-old male, did not develop following the administration of 10 μg TP or 5 μg EB at 4 days of age. The results of this study suggest that sexual differentiation of the hypothalamic regulation of GTH secretion is determined by testicular androgen, that this process is independent of normal ovarian activity, and that the masculinizing effect of EB in both male and female rats is not physiologic. The similar response of male and female rats to steroid hormones supports the hypothesis that sexual differentiation of neuronal elements may determine the capacity of the preoptic hypothalamus to regulate the cyclic discharge of GTH. (Endocrinology76: 226, 1965)