Significance of Neonatal Testicular Sex Steroids to Defeminize Anteroventral Periventricular Kisspeptin Neurons and the GnRH/LH Surge System in Male Rats
Significance of Neonatal Testicular Sex Steroids to Defeminize Anteroventral Periventricular Kisspeptin Neurons and the GnRH/LH Surge System in Male Rats
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DOI：
10.1095/biolreprod.109.078311
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发表时间：
2009-12-01
影响因子：
3.6
通讯作者：
Tsukamura, Hiroko
中科院分区：
文献类型：
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作者：
Homma, Tamami;Sakakibara, Mototsugu;Tsukamura, Hiroko
啮齿动物调节促性腺激素释放激素(GnRH)/促黄体生成素（LH）释放的脑机制存在性别分化。腹侧脑室周围核（AVPV）中的Kisspeptin神经元被认为是两性二态的，并参与GnRH/LH激增的产生。本研究旨在确定新生儿睾丸雄激素对AVPV kisspeptin表达和GnRH/LH激波产生系统去雌性化的意义。为此，我们测试了新生儿阉割是否使雄性大鼠AVPV kisspeptin神经元和LH生成系统雌性化，以及新生儿苯甲酸雌二醇（EB）治疗是否抑制雌性大鼠kisspeptin表达和LH激增。免疫组织化学、原位杂交和实时定量RT-PCR检测kisspeptin和Kiss1 mRNA的表达。雄性大鼠在出生后立即阉割，雌性大鼠在出生后第5天给予EB治疗。新生儿阉割导致遗传雄性大鼠AVPV kisspeptin肽和mRNA水平表达增加，并且在成年期雌二醇（E2）排卵前水平存在的情况下，动物表现出激增样的LH释放。另一方面，新生儿EB治疗降低了雌性大鼠AVPV kisspeptin神经元数量，导致e2诱导的LH激增缺失。半定量RT-PCR分析显示，新生儿类固醇操作影响Kiss1的表达，但对AVPV中神经肽（神经紧张素和丙氨酸）和神经递质（γ -氨基丁酸、谷氨酸和多巴胺）的酶或转运蛋白的基因表达没有显著影响，表明类固醇操作特异性影响Kiss1的表达。综上所述，我们目前的研究结果为新生儿睾丸雄激素导致遗传雄性大鼠AVPV kisspeptin表达减少和LH激增失败提供了生理学证据。因此，围产期睾丸雄激素引起AVPV kisspeptin系统的去雌性化，导致雄性大鼠的激增系统丧失，这是合理的。
The brain mechanism regulating gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release is sexually differentiated in rodents. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) have been suggested to be sexually dimorphic and involved in the GnRH/LH surge generation. The present study aimed to determine the significance of neonatal testicular androgen to defeminize AVPV kisspeptin expression and the GnRH/LH surge-generating system. To this end, we tested whether neonatal castration feminizes AVPV kisspeptin neurons and the LH surge-generating system in male rats and whether neonatal estradiol benzoate (EB) treatment suppresses the kisspeptin expression and the LH surge in female rats. Immunohistochemistry, in situ hybridization, and quantitative real-time RT-PCR were performed to investigate kisspeptin and Kiss1 mRNA expressions. Male rats were castrated immediately after birth, and females were treated with EB on postnatal Day 5. Neonatal castration caused an increase in AVPV kisspeptin expression at peptide and mRNA levels in the genetically male rats, and the animals showed surge-like LH release in the presence of the preovulatory level of estradiol (E2) at adulthood. On the other hand, neonatal EB treatment decreased the number of AVPV kisspeptin neurons and caused an absence of E2-induced LH surge in female rats. Semiquantitative RT-PCR analysis showed that neonatal steroidal manipulation affects Kiss1 expression but does not significantly affect gene expressions of neuropeptides (neurotensin and galanin) and enzymes or transporter for neurotransmitters (gamma-aminobutyric acid, glutamate, and dopamine) in the AVPV, suggesting that the manipulation specifically affects Kiss1 expressions. Taken together, our present results provide physiological evidence that neonatal testicular androgen causes the reduction of AVPV kisspeptin expression and failure of LH surge in genetically male rats. Thus, it is plausible that perinatal testicular androgen causes defeminization of the AVPV kisspeptin system, resulting in the loss of the surge system in male rats.