Inducible Kiss1 knockdown in the hypothalamic arcuate nucleus suppressed pulsatile secretion of luteinizing hormone in male mice
Inducible Kiss1 knockdown in the hypothalamic arcuate nucleus suppressed pulsatile secretion of luteinizing hormone in male mice
复制标题
DOI：
10.1262/jrd.2019-164
复制
发表时间：
2020-08-01
影响因子：
1.8
通讯作者：
Matsuda, Fuko
中科院分区：
文献类型：
--
作者：
Minabe, Shiori;Nakamura, Sho;Matsuda, Fuko
越来越多的证据表明，kisspeptin-GPR54 信号对于促性腺激素释放激素 (GnRH)/促性腺激素的分泌以及随后的哺乳动物生殖功能是不可或缺的。据报道，传统 Kiss] 敲除 (KO) 小鼠和大鼠不育。然而，迄今为止，还没有研究调查诱导型中枢 Kiss1 KO/敲低对雄性哺乳动物脉动促性腺激素释放的影响。在这里，我们报告了诱导条件 Kissl 敲低雄性小鼠的体内分析。这些小鼠是通过将驱动 Cre 重组酶的腺相关病毒 (AAV) 载体 (AAV-Cre) 或驱动 GFP 的 AAV 载体 (AAV-GFP，对照) 注射到 Kiss1-floxed 雄性小鼠的下丘脑弓状核 (ARC) 中产生的，其中 Kiss1 基因的外显子 3 与 loxP 位点进行 floxed。注射 AAV-Cre 4 周后，小鼠的 ARC Kiss1 表达细胞数量和黄体生成素 (LH) 脉冲频率均显着下降。有趣的是，尽管 ARC Kiss1 表达受到抑制，但在 AAV-Cre 注射后 8 周，脉冲性 LH 分泌仍然很明显。感染 AAV-GFP 的对照 Kissl-floxed 小鼠在 AAV-GFP 注射后 4 周和 8 周均显示出明显的 LH 脉冲和 ARC 中的 Kiss1 表达。雄性小鼠 ARC 中诱导性条件性 Kiss1 敲低的结果表明，ARC Kisspeptin 神经元负责雄性小鼠的脉冲性 LH 分泌，并表明恢复 GnRH/LH 脉冲生成的补偿机制的可能性。
Accumulating evidence suggests that kisspeptin-GPR54 signaling is indispensable for gonadotropin-releasing hormone (GnRH)/gonadotropin secretion and consequent reproductive functions in mammals. Conventional Kiss] knockout (KO) mice and rats are reported to be infertile. To date, however, no study has investigated the effect of inducible central Kiss1 KO/knockdown on pulsatile gonadotropin release in male mammals. Here we report an in vivo analysis of inducible conditional Kissl knockdown male mice. The mice were generated by a bilateral injections of either adeno-associated virus (AAV) vectors driving Cre recombinase (AAV-Cre) or AAV vectors driving GFP (AAV-GFP, control) into the hypothalamic arcuate nucleus (ARC) of Kiss1-floxed male mice, in which exon 3 of the Kiss1 gene were floxed with loxP sites. Four weeks after the AAV-Cre injection, the mice showed a profound decrease in the both number of ARC Kiss1-expressing cells and the luteinizing hormone (LH) pulse frequency. Interestingly, pulsatile LH secretion was apparent 8 weeks after the AAV-Cre injection despite the suppression of ARC Kiss1 expression. The control Kissl-floxed mice infected with AAV-GFP showed apparent LH pulses and Kiss1 expression in the ARC at both 4 and 8 weeks after the AAV-GFP injection. These results with an inducible conditional Kiss1 knockdown in the ARC of male mice suggest that ARC kisspeptin neurons are responsible for pulsatile LH secretion in male mice, and indicate the possibility of a compensatory mechanism that restores GnRH/LH pulse generation.