In order to gain a better understanding of the neurobiology of positive feedback on gonadotropin secretion we are studying the development and regulation of neurotransmitter expression in the anteroventral periventricular nucleus of the preoptic region (AVPV) of juvenile female rats. Glutamate is an important regulator of GnRH secretion during pubertal development, but its sites of action remain largely unknown. We have used histochemical methods to demonstrate that neurons in the AVPV express both NMDA (RI) and AMPA (GluR1, GluR2, and GluR3, but not GluR4-7) glutamate receptor subtypes. Treatment of ovariectomized juvenile rats with exogenous estradiol caused a significant increase in the ratio of GluR1/GluR2. However, neither levels of GluR3 mRNA, nor the GluR3/GluR2 ratio, were altered significantly by estrogen treatment. These findings suggest that estrogen may facilitate Ca2+ influx in the AVPV by inducing the expression of GluR1 and we are currently using calcium imaging to test this hypothesis directly. Sex steroid hormones also regulate the development of sexually dimorphic populations of neurons in the AVPV. By using mice that have mutations in either the estrogen receptor (ER) or androgen receptor (AR) we have determined that sexual differentiation of dopaminergic neurons in the AVPV is dependent on an intact ER, but appears to be independent of the AR. Moreover, we are using organotypic explants of the AVPV in vitro to study the direct effects of sex steroid hormones on the development of dopamine neurons in the AVPV. We have adapted this method for the study of primate brain development and experiments examining the role of hormones in regulating glutamatergic signaling in the nonhuman primate brain are in progress.
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