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(ER-β)在成年大鼠发育脑性分化中的生理作用以及对生殖神经内分泌的性别特异性调节。应用非等位原位杂交和免疫组织化学方法，我们发现ERβ在大鼠视前区前腹侧脑室周围核中的表达存在显著的性别差异。在距第三脑室室管膜表面50μm的范围内，动静脉动静脉内侧部ER mR NA阳性细胞数明显多于男性。成年雌性动静脉动静脉内ERα免疫反应阳性细胞中有83%的ERβ阳性细胞共存，在动静脉动静脉周围的第三脑室注入ERβ反义寡核苷酸可使动情持续天数显著延长，动静脉动静脉内ERβ免疫反应细胞数减少50%。这些发现支持了这一假说，即动静脉曲张中ERβ的激活是女性黄体生成素激增的典型调节事件。现在，我们通过向动静脉动静脉注入寡核苷酸来进一步研究ERβ和ERα在雌激素调节黄体生成素激增过程中的相互作用。

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.