title: Orphanin FQ-ORL-1 regulation of reproduction and reproductive behavior in the female.
abstract: 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.
authors: Department of Biological Sciences, California State University, Long Beach, California, USA. Electronic address: kevin.sinchak@csulb.edu.
authors: Kevin
authors: K
authors: Sinchak
authors: Department of Biological Sciences, California State University, Long Beach, California, USA.
authors: Lauren
authors: L
authors: Dalhousay
authors: Department of Pharmacological Sciences, University of California, Irvine, California, USA.
authors: Nayna
authors: N
authors: Sanathara
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D005260:Female; D006801:Humans; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018847:Opioid Peptides / Q000378:metabolism*; D010053:Ovary / Q000502:physiology; D011187:Posture; D011957:Receptors, Opioid / Q000819:agonists* / Q000378:metabolism; D012098:Reproduction; D043762:Reproductive Behavior; D012726:Sexual Behavior, Animal; D015398:Signal Transduction; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D009419:Nerve Tissue Proteins; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human
keywords: Estrogen receptor; Female reproduction; LH surge; Lordosis; Nociceptin; Opioid receptor-like receptor-1; Progesterone receptor, membrane estrogen receptors; Sexual receptivity; β-endorphin; μ-Opioid receptors