Silveira Marina Augusto, Furigo Isadora C, Zampieri Thais T, Bohlen Tabata M, de Paula Daniella G, Franci Celso Rodrigues, Donato Jose, Frazao Renata
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Mol Cell Endocrinol. 2017 Jun 15;448:55-65. doi: 10.1016/j.mce.2017.03.024. Epub 2017 Mar 23.
Previous studies have shown that kisspeptin neurons are important mediators of prolactin's effects on reproduction. However, the cellular mechanisms recruited by prolactin to affect kisspeptin neurons remain unknown. Using whole-cell patch-clamp recordings of brain slices from kisspeptin reporter mice, we observed that 20% of kisspeptin neurons in the anteroventral periventricular nucleus was indirectly depolarized by prolactin via an unknown population of prolactin responsive neurons. This effect required the phosphatidylinositol 3-kinase signaling pathway. No effects on the activity of arcuate kisspeptin neurons were observed, despite a high percentage (70%) of arcuate neurons expressing prolactin-induced STAT5 phosphorylation. To determine whether STAT5 expression in kisspeptin cells regulates reproduction, mice carrying Stat5a/b inactivation specifically in kisspeptin cells were generated. These mutants exhibited an early onset of estrous cyclicity, indicating that STAT5 transcription factors exert an inhibitory effect on the timing of puberty.
先前的研究表明， kisspeptin神经元是催乳素对生殖作用的重要介质。然而，催乳素影响kisspeptin神经元所涉及的细胞机制仍不清楚。利用kisspeptin报告基因小鼠脑片的全细胞膜片钳记录，我们观察到室旁核前腹侧20%的kisspeptin神经元通过一群未知的催乳素反应神经元被催乳素间接去极化。这种效应需要磷脂酰肌醇3-激酶信号通路。尽管有高比例（70%）的弓状核神经元表达催乳素诱导的STAT5磷酸化，但未观察到对弓状核kisspeptin神经元活性的影响。为了确定kisspeptin细胞中STAT5的表达是否调节生殖，我们构建了特异性在kisspeptin细胞中使Stat5a/b失活的小鼠。这些突变体表现出动情周期提前开始，表明STAT5转录因子对青春期时间有抑制作用。
