Sex steroids and the development of the newborn mouse hypothalamus and preoptic area in vitro. II. Morphological correlates and hormonal specificity.

In studies designed to elucidate morphogenetic mechanisms involved in the neurogenesis of sexual differentiation of the brain, estradiol or testosterone was added to organotypic cultures of the newborn mouse hypothalamus and preoptic area. Both gonadal hormones selectively accelerated and enhanced neuritic proliferation in specific regions of the preoptic area and infundibular/premamillary levels. This regional localization suggests specific induction of neuritic branching perhaps only in those neurons shown by autoradiography to contain the steroid receptor. The significance of estradiol per se is emphasized by the reduction and retardation of neuritic outgrowth in those same regions following exposure to steroid-deficient medium or blockade of the nuclear receptor (CI-628) and by the failure of testosterone alone to induce a significant response. The importance of aromatization of androgen to estradiol is supported by the failure of non-aromatizable 5 alpha-dihydrotestosterone to elicit an effect even in the presence of estradiol. This apparent hormonal specificity suggests that the neuritic response may be a component of sexual differentitation and that the trophic effects of estradiol may influence significantly the ontogeny of target neural circuits in the brain of both genders.