Department of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, United States.
Harvard Medical School, Boston, United States.
Elife. 2018 Dec 19;7:e40476. doi: 10.7554/eLife.40476.
Neurokinin B (NKB) signaling is critical for reproduction in all studied species. The existing consensus is that NKB induces GnRH release via kisspeptin () stimulation in the arcuate nucleus. However, the stimulatory action of NKB is dependent on circulating estrogen (E) levels, without which, NKB inhibits luteinizing hormone (LH) release. Importantly, the evidence supporting the kisspeptin-dependent role of NKB, derives from models of persistent hypogonadal state [e.g. knock-out (KO) mice], with reduced E levels. Here, we demonstrate that in the presence of E, NKB signaling induces LH release in a kisspeptin-independent manner through the activation of NK3R (NKB receptor) neurons in the posterodorsal medial amygdala (MePD). Importantly, we show that chemogenetic activation of MePD Kiss1 neurons induces LH release, however, the stimulatory action of NKB in this area is Kiss1 neuron-independent. These results document the existence of two independent neuronal circuitries within the MePD that regulate reproductive function in females.
This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
神经激肽 B(NKB)信号对于所有研究物种的生殖都至关重要。现有共识认为,NKB 通过刺激弓状核中的 kisspeptin()诱导 GnRH 释放。然而,NKB 的刺激作用取决于循环雌激素(E)水平,没有 E,NKB 会抑制促黄体生成素(LH)的释放。重要的是,支持 NKB 通过 kisspeptin 发挥作用的证据来自于持续低促性腺激素状态的模型[例如 knock-out(KO)小鼠],这些模型中的 E 水平降低。在这里,我们证明,在 E 的存在下,NKB 信号通过激活后背侧内侧杏仁核(MePD)中的 NK3R(NKB 受体)神经元,以 kisspeptin 非依赖性的方式诱导 LH 释放。重要的是,我们表明 MePD Kiss1 神经元的化学遗传激活会诱导 LH 释放,然而,NKB 在该区域的刺激作用与 Kiss1 神经元无关。这些结果证明了 MePD 内存在两种独立的神经元回路,它们调节雌性的生殖功能。
本文经过了编辑过程,作者在该过程中决定如何处理同行评审期间提出的问题。审稿人的评估是所有问题都已得到解决(见评审意见)。