Weems Peyton, Smith Jeremy, Clarke Iain J, Coolen Lique M, Goodman Robert L, Lehman Michael N
Neuroscience Graduate Program, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, USA.
School of Anatomy, Physiology and Human Biology, The University of Western Australia, Nedlands, Western Australia, Australia.
Endocrinology. 2017 Apr 1;158(4):831-841. doi: 10.1210/en.2016-1830.
Seasonal reproduction in sheep is primarily due to a dramatic increase in the ability of estradiol (E2) to inhibit the pulsatile secretion of gonadotropin-releasing hormone (GnRH) during the nonbreeding season [anestrus (ANS)]. Recent findings suggest that kisspeptin/neurokinin B/dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in conveying this negative feedback influence, with dopaminergic projections from the retrochiasmatic area acting upon KNDy cells to decrease kisspeptin release and thus inhibit GnRH pulses. However, several questions remain unanswered: (1) Are the coexpressed KNDy peptides, neurokinin B (NKB) and dynorphin, under seasonal regulation similar to kisspeptin? (2) Are seasonal changes in these peptides and their colocalization of D2 dopamine receptors (D2Rs) steroid dependent? and (3) Do KNDy neurons receive direct input from dopaminergic terminals? We used dual- and triple-label immunofluorescence to analyze brain sections through the ARC of ovariectomized (OVX) and OVX plus E2 ewes perfused during either the breeding season or ANS. Results showed (1) steroid-dependent and steroid-independent seasonal changes in kisspeptin and NKB, but not dynorphin, immunoreactivity; (2) increased D2R coexpression during ANS that was dependent on the presence of E2; and (3) evidence that KNDy cells receive direct contact from dopaminergic terminals and that this input increases during ANS. These results support the hypothesis that dopamine acts to inhibit GnRH secretion in ANS by directly suppressing the activity of ARC KNDy neurons, and implicate NKB as well as kisspeptin in seasonal shifts in E2-negative feedback in the sheep.
绵羊的季节性繁殖主要是由于在非繁殖季节[发情间期（ANS）]雌二醇（E2）抑制促性腺激素释放激素（GnRH）脉冲式分泌的能力急剧增强。最近的研究结果表明，弓状核（ARC）的亲吻素/神经激肽B/强啡肽（KNDy）神经元在传递这种负反馈影响中起关键作用，视交叉后区的多巴胺能投射作用于KNDy细胞以减少亲吻素释放，从而抑制GnRH脉冲。然而，仍有几个问题未得到解答：（1）共表达的KNDy肽、神经激肽B（NKB）和强啡肽是否与亲吻素一样受季节性调节？（2）这些肽及其D2多巴胺受体（D2Rs）共定位的季节性变化是否依赖于类固醇？以及（3）KNDy神经元是否接受来自多巴胺能终末的直接输入？我们使用双重和三重标记免疫荧光法分析在繁殖季节或发情间期灌注的去卵巢（OVX）和OVX加E2母羊通过ARC的脑切片。结果显示：（1）亲吻素和NKB免疫反应性存在依赖于类固醇和不依赖于类固醇的季节性变化，但强啡肽没有；（2）发情间期D2R共表达增加，这依赖于E2的存在；（3）有证据表明KNDy细胞接受来自多巴胺能终末的直接接触，并且这种输入在发情间期增加。这些结果支持以下假设，即多巴胺通过直接抑制ARC KNDy神经元的活性来抑制发情间期的GnRH分泌，并表明NKB以及亲吻素参与了绵羊E2负反馈的季节性变化。
