Stincic Todd L, Rønnekleiv Oline K, Kelly Martin J
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239, United States.
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239, United States; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, United States.
Steroids. 2021 Apr;168:108428. doi: 10.1016/j.steroids.2019.108428. Epub 2019 Jun 20.
Reproduction and energy balance are inextricably linked in order to optimize the evolutionary fitness of an organism. With insufficient or excessive energy stores a female is liable to suffer complications during pregnancy and produce unhealthy or obesity-prone offspring. The quintessential function of the hypothalamus is to act as a bridge between the endocrine and nervous systems, coordinating fertility and autonomic functions. Across the female reproductive cycle various motivations wax and wane, following levels of ovarian hormones. Estrogens, more specifically 17β-estradiol (E2), coordinate a triumvirate of hypothalamic neurons within the arcuate nucleus (ARH) that govern the physiological underpinnings of these behavioral dynamics. Arising from a common progenitor pool of cells, this triumvirate is composed of the kisspeptin (Kiss1), proopiomelanocortin (POMC), and neuropeptide Y/agouti-related peptide (AgRP) neurons. Although the excitability of these neuronal subpopulations is subject to genomic and rapid estrogenic regulation, kisspeptin neurons are the most sensitive, reflecting their integral function in female fertility. Based on the premise that E2 coordinates autonomic functions around reproduction, we will review the recent findings on the synaptic interactions between Kiss1, AgRP and POMC neurons and how the rapid membrane-initiated and intracellular signaling cascades activated by E2 in these neurons are critical for control of homeostatic functions supporting reproduction.
生殖与能量平衡紧密相连，以优化生物体的进化适应性。能量储备不足或过多时，女性在孕期容易出现并发症，并产下不健康或易肥胖的后代。下丘脑的核心功能是充当内分泌系统和神经系统之间的桥梁，协调生育能力和自主功能。在女性生殖周期中，各种动机随卵巢激素水平的变化而消长。雌激素，更具体地说是17β-雌二醇（E2），协调弓状核（ARH）内的一组下丘脑神经元，这些神经元控制着这些行为动态的生理基础。这组神经元起源于共同的祖细胞池，由 kisspeptin（Kiss1）、阿黑皮素原（POMC）和神经肽Y/刺鼠相关肽（AgRP）神经元组成。尽管这些神经元亚群的兴奋性受到基因组和快速雌激素调节的影响，但kisspeptin神经元最为敏感，这反映了它们在女性生育中的重要作用。基于E2协调生殖周围自主功能的前提，我们将综述关于Kiss1、AgRP和POMC神经元之间突触相互作用的最新研究结果，以及E2在这些神经元中激活的快速膜起始和细胞内信号级联反应如何对支持生殖的稳态功能控制至关重要。
