Physiological Role of Estrogen Receptor β Positive Cells in Liteinizing hormone surge.

本研究旨在探讨雌激素受体β (estrogen receptor β, ERβ)在成年大鼠发育中脑性别分化和生殖神经内分泌性别特异性调节中的生理作用。通过非同位素原位杂交和免疫组化，我们发现大鼠视前区腹侧脑室周围核（AVPV）中ERβ的表达存在显著的性别差异。在距第三脑室室管膜表面50 μm范围内的AVPV内侧，可见ERβ mRNA阳性细胞数量明显多于男性。在第14天检查时，雄性新生儿的睾丸切除术或雌性幼崽的雌激素治疗逆转了大脑表型。在成年女性的AVPV中，ERα免疫反应性共定位在83%的ERβ mrna阳性细胞中。将ERβ反义寡核苷酸注入AVPV附近的第三脑室，可显著延长连续发情天数，并使AVPV中ERβ免疫反应细胞数量减少50%。这些发现支持了AVPV中ERβ的激活是雌性激素诱导黄体生成素激增的重要调节事件的假设。我们现在利用寡核苷酸注入AVPV进一步研究ERβ和ERα在雌激素调控促黄体生成素激增中的相互作用。

In this project, we investigated the physiological role of estrogen receptor β (ERβ) in sexual differentiation of developing brain and sex specific regulation of reproductive neuroendocrinology in the adult rats. By using non-isotoic in situ hybridizaiton and immunohistochemistry, we found a strikingly sex difference expression of the ERβ in the anteroventral periventricular nucleus (AVPV) of the rat preoptic area. In females more than in males, a significantly of larger number ERβ mRNA positive cells were visualized in the medial portion of the AVPV within 50 μm form the ependymal surface of the third ventricle. Orchidectomy of male neonates or estrogen treatment of female pups reversed the brain phenotype when examined on day 14. In the AVPV of adult females, ERα immunoreactivity colocalized in 83% of ERβ mRNA-positive cells.Infusion of ERβ antisense oligonucleotide into the third ventricle in the vicinity of the AVPV resulted in significantly longer days of successive estrus and a 50% reduction in the number of ERβ-immunoreactive cells in the AVPV. These findings provide support for the hypothesis that activation of ERβ in the AVPV is an important regulatory event in the female-typical induction of luteinizing hormone surge by estrogen. We further examine the interaction between ERβ and ERα in the regulation of luteinizing hormone surge by estrogen by using oligonucleotide infusion into the AVPV now.