Nakao Kimihiko, Iwata Kinuyo, Takeshita Toshiyuki, Ozawa Hitoshi
Department of Reproductive Medicine, Perinatology and Gynecologic Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan.
Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan.
Neurosci Lett. 2018 Feb 5;665:135-139. doi: 10.1016/j.neulet.2017.12.002. Epub 2017 Dec 5.
Zucker fatty (ZF) rats are considered to be an obese model due to leptin receptor abnormality and such rats show infertility. Pulsatile gonadotropin-releasing hormone/luteinizing hormone (LH) secretion, which is important for follicular development in females, is considered to be controlled by KNDy neurons coexpressing kisspeptin, neurokinin B (NKB), and dynorphin A (DynA), encoded by Kiss1, Tac3, and Pdyn, respectively, in the hypothalamic arcuate nucleus (ARC). The purpose of this study is to examine the expression of KNDy neurons in female ZF rats by histochemical approach because pulsatile LH secretion is suppressed. Zucker lean (ZL) rats served as a control group. Animals were ovariectomized and subcutaneously implanted with a silicon tube containing estradiol to produce plasma level of estradiol during diestrus. Plasma LH levels decreased in ZF rats compared with ZL rats. The expressions of each mRNA (Kiss1, Tac3, and Pdyn) and each peptide (kisspeptin, NKB, and DynA) in the ARC significantly decreased in ZF rats compared with ZL rats. However, the number of Kiss1 neurons in the anterior ventral periventricular nucleus did not significantly differ between the two groups. These results suggest that dysfunction of leptin signaling negatively affects KNDy neurons in the ARC, resulting in reproductive dysfunction caused by suppression of the LH pulse.
由于瘦素受体异常，Zucker肥胖（ZF）大鼠被认为是一种肥胖模型，且此类大鼠表现出不育。促性腺激素释放激素/黄体生成素（LH）的脉冲式分泌对雌性卵泡发育很重要，被认为受下丘脑弓状核（ARC）中共同表达 kisspeptin、神经激肽B（NKB）和强啡肽A（DynA）的KNDy神经元控制，它们分别由Kiss1、Tac3和Pdyn编码。本研究的目的是通过组织化学方法检测雌性ZF大鼠中KNDy神经元的表达，因为LH的脉冲式分泌受到了抑制。Zucker瘦素（ZL）大鼠作为对照组。对动物进行卵巢切除，并皮下植入含雌二醇的硅胶管，以在动情间期产生雌二醇的血浆水平。与ZL大鼠相比，ZF大鼠的血浆LH水平降低。与ZL大鼠相比，ZF大鼠ARC中各mRNA（Kiss1、Tac3和Pdyn）和各肽（kisspeptin、NKB和DynA）的表达显著降低。然而，两组之间腹侧室旁核前部的Kiss1神经元数量没有显著差异。这些结果表明，瘦素信号功能障碍对ARC中的KNDy神经元产生负面影响，导致LH脉冲受抑制引起的生殖功能障碍。
