Sex steroid receptors in the perinatal rat brain

Many sex differences in the regulation of reproductive function in rats are the result of a differentiation of the brain which occurs neonatally. Although injections of either androgens or estrogens are capable during the neonatal period of altering hypothalamic systems involved in reproductive behavior and gonadotropin regulation, the physiological role of each type of hormone has not been clearly established. In both sexes, circulating estrogens are normally kept from interacting with estrogen receptors in the limbic brain by the high levels of alpha-fetoprotein in the blood. The local aromatization of androgens in the brain could circumvent alpha-fetoprotein, since androgens do not bind to this serum protein. The "paromatization hypothesis" states that testosterone, which is abundant in neonatal male circulation but absent in females, is locally converted to estradiol in the limbic brain. There it binds to estrogen receptor proteins to produce tissue differentiation. The ontogeny of estradiol binding proteins in limbic areas is consistent with the aromatization hypothesis, with a rapid increase in receptor levels occurring shortly after birth. Also, the presence of endogenous estradiol-receptor complexes has been demonstrated in the cell nuclei of male neonates but not female neonales. Furthermore, the presence of estradiol binding proteins in other regions of the neonatal male and female brain suggests an additional role of estradiol. unknown as of yet. Several studies with agents which block the aromatization of androgens to estrogens or the binding of estrogens to their receptors are consistent with the aromatization hypothesis, since these agents prevent the differentiation of intact neonatal males. However, specific androgen binding proteins are also present in neonatal brains, and androgen-receptor complexes can be found in cell nuclei of neonates after an injection of tritiated androgen. The possible involvement of these receptors in sexual differentiation of the brain is suggested by the finding that an antiandrogen inhibits both the binding of androgens (but not estrogens) and the differentiation of males.