Estradiol Upregulates Progesterone Receptor and Orphanin FQ Colocalization in Arcuate Nucleus Neurons and Opioid Receptor-Like Receptor-1 Expression in Proopiomelanocortin Neurons That Project to the Medial Preoptic Nucleus in the Female Rat

Background: Ovarian steroids regulate sexual receptivity in the female rat by acting on neurons that converge on proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH) that project to the medial preoptic nucleus (MPN). Estradiol rapidly activates these neurons to release 3-endorphin that activates MPN p-opioid receptors (MOP) to inhibit lordosis. Lordosis is facilitated by the subsequent action of progesterone that deactivates the estradiolinduced MPN MOP activation. Orphanin FQ (OFQ/N; also known as nociceptin) infusions into the ARH, like progesterone, deactivate MPN MOP and facilitate lordosis in estradiolprimed rats. OFQ/N reduces the activity of ARH 3-endorphin neurons through post-and presynaptic mechanisms via its cognate receptor, ORL-1. Methods: We tested the hypotheses that progesterone receptors (PR) are expressed in ARH OFQ/N neurons by imnnunohistochemistry and ORL-1 is expressed in POMC neurons that project to the MPN by corn- bining Fluoro-Gold injection into the MPN and double-label fluorescent in situ hybridization (FISH). We also hypothesized that estradiol increases coexpression of PR-OFQ/N and ORL-1-POMC in ARH neurons of ovariectonnized rats. Results: The number of PR-and OFQ/N-immunopositive ARH neurons was increased as was their colocalization by estradiol treatment. FISH for ORL-1 and POMC mRNA revealed a subpopulation of ARH neurons that was triple labeled, indicating these neurons project to the MPN and coexpress ORLI and POMC mRNA. Estradiol was shown to upregulate ORLI and POMC expression in MPN-projecting ARH neurons. Conclusion: Estradiol upregulates the ARH OFQ/N-ORL-1 system projecting to the MPN that regulates lordosis. (C) 2014 S. Karger AG, Basel