Hu M H, Li X F, McCausland B, Li S Y, Gresham R, Kinsey-Jones J S, Gardiner J V, Sam A H, Bloom S R, Poston L, Lightman S L, Murphy K G, O'Byrne K T
Division of Women's Health (M.H.H., X.F.L., B.M., S.Y.L., R.G., L.P., K.T.O.), Faculty of Life Sciences and Medicine, King's College London, Guy's Campus, London SE1 1UL, United Kingdom; Section of Investigative Medicine (J.S.K.-J., J.V.G., A.H.S., S.R.B., K.G.M.), Division of Diabetes, Endocrinology, and Metabolism, Imperial College London, London W12 0NN, United Kingdom; and Henry Wellcome Laboratory for Integrative Neuroscience and Endocrinology (S.L.L.), University of Bristol, Bristol BS13NY, United Kingdom.
Endocrinology. 2015 Jul;156(7):2619-31. doi: 10.1210/en.2014-1655. Epub 2015 Apr 15.
Kisspeptin plays a critical role in pubertal timing and reproductive function. In rodents, kisspeptin perikarya within the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei are thought to be involved in LH pulse and surge generation, respectively. Using bilateral microinjections of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC or AVPV of female rats at postnatal day 10, we investigated the relative importance of these two kisspeptin populations in the control of pubertal timing, estrous cyclicity, and LH surge and pulse generation. A 37% knockdown of kisspeptin in the AVPV resulted in a significant delay in vaginal opening and first vaginal estrous, abnormal estrous cyclicity, and reduction in the occurrence of spontaneous LH surges, although these retained normal amplitude. This AVPV knockdown had no effect on LH pulse frequency, measured after ovariectomy. A 32% reduction of kisspeptin in the ARC had no effect on the onset of puberty but resulted in abnormal estrous cyclicity and decreased LH pulse frequency. Additionally, the knockdown of kisspeptin in the ARC decreased the amplitude but not the incidence of LH surges. These results might suggest that the role of AVPV kisspeptin in the control of pubertal timing is particularly sensitive to perturbation. In accordance with our previous studies, ARC kisspeptin signaling was critical for normal pulsatile LH secretion in female rats. Despite the widely reported role of AVPV kisspeptin neurons in LH surge generation, this study suggests that both AVPV and ARC populations are essential for normal LH surges and estrous cyclicity.
kisspeptin在青春期启动和生殖功能中起着关键作用。在啮齿动物中，下丘脑弓状核（ARC）和室旁前腹侧核（AVPV）内的kisspeptin神经元胞体分别被认为参与促黄体生成素（LH）脉冲和高峰的产生。我们在出生后第10天对雌性大鼠的ARC或AVPV进行双侧显微注射编码kisspeptin反义序列的重组腺相关病毒，研究了这两种kisspeptin群体在控制青春期启动、发情周期以及LH高峰和脉冲产生方面的相对重要性。AVPV中kisspeptin敲低37%导致阴道开口和首次阴道发情显著延迟、发情周期异常以及自发性LH高峰出现次数减少，不过这些高峰的幅度保持正常。这种AVPV敲低对卵巢切除术后测量的LH脉冲频率没有影响。ARC中kisspeptin减少32%对青春期启动没有影响，但导致发情周期异常和LH脉冲频率降低。此外，ARC中kisspeptin敲低降低了LH高峰的幅度，但未降低其发生率。这些结果可能表明，AVPV kisspeptin在控制青春期启动方面的作用对干扰特别敏感。与我们之前的研究一致，ARC kisspeptin信号传导对雌性大鼠正常的LH脉冲分泌至关重要。尽管AVPV kisspeptin神经元在LH高峰产生中的作用已被广泛报道，但本研究表明，AVPV和ARC群体对于正常的LH高峰和发情周期都是必不可少的。
