Kisspeptin - a dual physiological role in the hypothalamic control of reproduction

Kisspeptin是一种54个氨基酸的神经肽，最近被发现是一种对青春期发育和生殖至关重要的下丘脑-垂体-性腺（HPG）轴的有效刺激物。除了性成熟期间表达的变化外，kisspeptin似乎在不同的下丘脑核中有不同的表达。性腺切除增加了弓形核（arc）中Kiss1的表达，而性类固醇替代使其表达恢复到完整动物[2]的水平，提示arc kisspeptin调节了性类固醇对GnRH分泌的负反馈。相比之下，在腹侧脑室周围核（AVPV）中，性腺切除术降低了Kiss1的表达，而性类固醇替代使其恢复。然而，kisspeptin和这些神经元群在青春期发育和成年生殖中的确切生理作用目前尚不清楚。为了阐明其生理作用，我们旨在确定特异性抑制kisspeptin在arc和AVPV中的表达对雄性和雌性成年大鼠青春期发育和生殖的影响，并表征这些核中表达kisspeptin的神经元。这些研究将为生殖疾病的潜在治疗靶点提供有价值的信息。

Kisspeptin is a 54 amino acid neuropeptide, recently identified as a potent stimulator of the hypothalamic-pituitary-gonadal (HPG) axis that is crucial for pubertal development and reproduction. Beyond the changes in expression during sexual maturation, kisspeptin appears to undergo differential expression in distinct hypothalamic nuclei. Gonadectomy increases Kiss1 expression in the arcuate nucleus (arc), and sex steroid replacement reduces expression back to that of intact animals [2], suggesting that arc kisspeptin modulates the negative feedback on GnRH secretion exerted by sex steroids. By contrast, in the anteroventral periventricular nucleus (AVPV) gonadectomy decreases Kiss1 expression and sex steroid replacement restores it. However, the precise physiological role of kisspeptin and these neuronal populations in pubertal development and adult reproduction is currently unknown. To elucidate its physiological role we aim to determine the effect of specifically suppressing kisspeptin expression in the arc and AVPV on pubertal development and reproduction and to characterise kisspeptin-expressing neurons in these nuclei in male and female adult rats. These studies will provide valuable information on potential therapeutic targets in reproductive disorders.