Sinchak Kevin, Dalhousay Lauren, Sanathara Nayna
Department of Biological Sciences, California State University, Long Beach, California, USA.
Department of Biological Sciences, California State University, Long Beach, California, USA.
Vitam Horm. 2015;97:187-221. doi: 10.1016/bs.vh.2014.11.002. Epub 2015 Jan 14.
Orphanin FQ (OFQ/N) and its receptor, opioid receptor-like receptor-1 (ORL-1), are expressed throughout steroid-responsive limbic and hypothalamic circuits that regulate female ovarian hormone feedback and reproductive behavior circuits. The arcuate nucleus of the hypothalamus (ARH) is a brain region that expresses OFQ/N and ORL-1 important for both sexual behavior and modulating estradiol feedback loops. Within the ARH, the activation of the OFQ/N-ORL-1 system facilitates sexual receptivity (lordosis) through the inhibition of β-endorphin neuronal activity. Estradiol initially activates ARH β-endorphin neurons to inhibit lordosis. Simultaneously, estradiol upregulates coexpression of OFQ/N and progesterone receptors and ORL-1 in ARH β-endorphin neurons. Ovarian hormones regulate pre- and postsynaptic coupling of ORL-1 to its G protein-coupled signaling pathways. When the steroid-primed rat is nonreceptive, estradiol acts pre- and postsynaptically to decrease the ability of the OFQ/N-ORL-1 system to inhibit ARH β-endorphin neurotransmission. Conversely, when sexually receptive, ORL-1 signaling is restored to inhibit β-endorphin neurotransmission. Although steroid signaling that facilitates lordosis converges to deactivate ARH β-endorphin neurons, estradiol-only facilitation of lordosis requires the activation of ORL-1, but estradiol+progesterone does not, indicating that multiple circuits mediate ovarian hormone signaling to deactivate ARH β-endorphin neurons. Research on the role of OFQ/N-ORL-1 in ovarian hormone feedback loops is just beginning. In the rat, OFQ/N may act to terminate gonadotropin-releasing hormone and luteinizing hormone release under positive and negative feedbacks. In the ewe, it appears to directly inhibit gonadotropin-releasing hormone release to mediate progesterone-negative feedback. As a whole, the localization and actions of OFQ/N-ORL-1 system indicate that it may mediate the actions of estradiol and progesterone to synchronize reproductive behavior and ovarian hormone feedback loops.
孤啡肽（OFQ/N）及其受体，即阿片样受体-1（ORL-1），在调节雌性卵巢激素反馈和生殖行为回路的类固醇反应性边缘系统和下丘脑回路中均有表达。下丘脑弓状核（ARH）是一个表达OFQ/N和ORL-1的脑区，这对性行为和调节雌二醇反馈回路都很重要。在ARH内，OFQ/N-ORL-1系统的激活通过抑制β-内啡肽神经元活动促进性接受能力（脊柱前凸）。雌二醇最初激活ARHβ-内啡肽神经元以抑制脊柱前凸。同时，雌二醇上调ARHβ-内啡肽神经元中OFQ/N与孕激素受体以及ORL-1的共表达。卵巢激素调节ORL-1与其G蛋白偶联信号通路的突触前和突触后偶联。当经类固醇预处理的大鼠不接受时，雌二醇在突触前和突触后起作用，降低OFQ/N-ORL-1系统抑制ARHβ-内啡肽神经传递的能力。相反，当具有性接受能力时，ORL-1信号传导得以恢复以抑制β-内啡肽神经传递。尽管促进脊柱前凸的类固醇信号传导会汇聚以使ARHβ-内啡肽神经元失活，但仅雌二醇促进脊柱前凸需要ORL-1的激活，而雌二醇+孕酮则不需要，这表明多个回路介导卵巢激素信号传导以使ARHβ-内啡肽神经元失活。关于OFQ/N-ORL-1在卵巢激素反馈回路中作用的研究才刚刚开始。在大鼠中，OFQ/N可能在正反馈和负反馈下终止促性腺激素释放激素和黄体生成素的释放。在母羊中，它似乎直接抑制促性腺激素释放激素的释放以介导孕酮负反馈。总体而言，OFQ/N-ORL-1系统的定位和作用表明它可能介导雌二醇和孕酮的作用，以使生殖行为和卵巢激素反馈回路同步。
