Effect of neuronal nitric oxide synthase serine-1412 phosphorylation on hypothalamic-pituitary-ovarian function and leptin response
Effect of neuronal nitric oxide synthase serine-1412 phosphorylation on hypothalamic-pituitary-ovarian function and leptin response
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DOI：
10.1093/biolre/ioaa025
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发表时间：
2020-06-01
影响因子：
3.6
通讯作者：
Hurt, K. Joseph
中科院分区：
文献类型：
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作者：
Guerra, Damian D.;Bok, Rachael;Hurt, K. Joseph
下丘脑神经元一氧化氮合酶（nNOS）通过刺激促性腺激素释放激素（GnRH）的分泌，进而促进黄体生成素（LH）的释放和排卵，从而增强成年雌性啮齿动物的生育能力。下丘脑nNOS激活的机制尚不清楚，但可能通过nNOS丝氨酸1412 （S1412）磷酸化，增加nNOS活性和其他器官系统的生理NO效应。据报道，在雌性啮齿动物中，下丘脑nNOS S1412磷酸化在发情前或发情期间急性瘦素暴露时增加。为了确定nNOS S1412是否调控雌性小鼠的生殖，我们比较了野生型和nNOS丝氨酸1412 ->丙氨酸（nNOS(S1412A)）敲入雌性小鼠的生殖解剖、发情周期、期比和繁殖力。我们还测量了下丘脑GnRH和血清LH、促卵泡激素（FSH）、雌二醇和孕酮在绝经小鼠腹腔注射瘦素后的变化。各基因型的脏器重量和组织学没有差异。野生型和nNOS（S1412A）小鼠的卵巢原始卵泡、窦卵泡和黄体相似。同样，发情周期和相长也没有差异，繁殖力也不显著。黄体生成素、卵泡刺激素、雌二醇或黄体酮的基因型之间没有差异。与之前的研究相反，我们的工作表明nNOS S1412磷酸化对于正常的下丘脑-垂体-卵巢功能和正常的动情周期是必不可少的。这些发现对目前nNOS磷酸化调控生育的模型具有重要意义。nNOS丝氨酸-1412-丙氨酸敲入小鼠表现出正常的动情周期和下丘脑-垂体-卵巢（hp -o）功能。
Hypothalamic neuronal nitric oxide synthase (nNOS) potentiates adult female fertility in rodents by stimulating gonadotropin releasing hormone (GnRH) secretion, which in turn promotes luteinizing hormone (LH) release and ovulation. The mechanism of hypothalamic nNOS activation is not clear but could be via nNOS serine1412 (S1412) phosphorylation, which increases nNOS activity and physiologic NO effects in other organ systems. In female rodents, hypothalamic nNOS S1412 phosphorylation reportedly increases during proestrus or upon acute leptin exposure during diestrus. To determine if nNOS S1412 regulates female reproduction in mice, we compared the reproductive anatomy, estrous cycle duration and phase proportion, and fecundity of wild-type and nNOS serine1412 -> alanine (nNOS(S1412A)) knock-in female mice. We also measured hypothalamic GnRH and serum LH, follicle stimulating hormone (FSH), estradiol, and progesterone in diestrus mice after intraperitoneal leptin injection. Organ weights and histology were not different by genotype. Ovarian primordial follicles, antral follicles, and corpora lutea were similar for wild-type and nNOS(S1412A) mice. Likewise, estrous cycle duration and phase length were not different, and fecundity was unremarkable. There were no differences among genotypes for LH, FSH, estradiol, or progesterone. In contrast to prior studies, our work suggests that nNOS S1412 phosphorylation is dispensable for normal hypothalamic-pituitary-ovarian function and regular estrous cycling. These findings have important implications for current models of fertility regulation by nNOS phosphorylation.Summary sentence nNOS serine-1412-alanine knock-in mice demonstrate normal estrous cycles and hypothalamicpituitary-ovarian (H-P-O) function.