An NIMH Research Scientist Award is requested. Studies on the mechanism of steroid hormone action in controlling neural, endocrine, and behavioral aspects of sexual differentiation are proposed using ferrets. The ontogeny of estradiol receptors in the forebrain and the migration of neurons along processes of radial glia into the preoptic/anterior hypothalamic area (POA/AH) will be compared in fetal males and females using immunocytochemical and autoradiographic methods. The results should help establish how estradiol acts prenatally to promote the formation in male ferrets of a sexually dimorphic male nucleus of the dorsal POA/AH (Mn- POA/AH), which is absent in females. The ability of coital stimulation to activate the expression of the proto-oncogene, c-fos, in gonadotropin- releasing-hormone-containing (GnRH) neurons as well as other neurons of the forebrain will also be compared in males and females. These studies may help explain the previously observed sex difference in the response of the ferret's pituitary-gonadal axis to mating, and should show whether the male's Mn-POA/AH contributes to this functional dimorphism. Additional studies on the possible contribution of the Mn-POA/AH to psychosexual function in males will include an analysis of the effects of neurotoxic lesions of this structure on the development and adult expression of sex partner preference as well as other motivational and performance aspects of mating. Finally, I propose to study the possible interaction in male ferrets between early postnatal social stimulation, derived from peers as well as the mother, and the action of testosterone in controlling the sexual differentiation of sex partner preference, sexual motivation, and coital behavior. The incidence of maternal licking of the genital region of male versus female ferret kits and possible consequences for the neonatal secretion of testosterone, which is critical for the completion of psychosexual differentiation in males, will be assessed. These mechanistic studies of steroid action using a higher mammalian model, the ferret, should provide insight into the control of neural, endocrine, and behavioral aspects of sexual differentiation in man.
