title: 17β-estradiol rapidly facilitates lordosis through G protein-coupled estrogen receptor 1 (GPER) via deactivation of medial preoptic nucleus μ-opioid receptors in estradiol primed female rats.
abstract: In female rats sexual receptivity (lordosis) can be induced with either a single large dose of estradiol benzoate (EB), or a priming dose of EB that does not induce sexual receptivity followed by 17β-estradiol (E2). Estradiol priming initially inhibits lordosis through a multi-synaptic circuit originating in the arcuate nucleus of the hypothalamus (ARH) that activates and internalizes μ-opioid receptors (MOR) in medial preoptic nucleus (MPN) neurons. Lordosis is facilitated when MPN MOR are deactivated after the initial estradiol-induced activation. We tested the hypothesis that E2 given 47.5 h post EB acts rapidly through G protein-coupled estrogen receptor 1 (GPER) in the ARH to deactivate MPN MOR and facilitate lordosis. Ovariectomized Long Evans rats implanted with a third ventricle cannula were primed with 2 μg EB. DMSO control, E2, or G1 (GPER selective agonist) was infused 47.5 h later, and rats were tested for sexual receptivity. E2 and G1 infusions significantly increased levels of sexual receptivity compared to DMSO controls and pretreatment with G15 (GPER antagonist) blocked the facilitation of sexual receptivity. Brains were processed for MPN MOR immunohistochemistry to measure MPN MOR activation levels. E2 and G1 both significantly reduced MPN MOR activation compared to DMSO controls, while pretreatment with G15 blocked MPN MOR deactivation. In another group of EB treated ovariectomized rats, GPER immunofluorescence positive staining was observed throughout the ARH. Together these data indicate that in the 2 μg EB primed rat, E2 rapidly signals through GPER in the ARH to deactivate MPN MOR and facilitate lordosis.
authors.affiliation: Department of Biological Sciences, California State University, Long Beach, Long Beach, CA, United States.
authors.forename: Nathan
authors.initials: N
authors.lastname: Long
authors.affiliation: Department of Biological Sciences, California State University, Long Beach, Long Beach, CA, United States.
authors.forename: Chhorvann
authors.initials: C
authors.lastname: Serey
authors.affiliation: Department of Biological Sciences, California State University, Long Beach, Long Beach, CA, United States. Electronic address: Kevin.sinchak@csulb.edu.
authors.forename: Kevin
authors.initials: K
authors.lastname: Sinchak
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011187:Posture / Q000502:physiology*; D011301:Preoptic Area / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism*; D012726:Sexual Behavior, Animal / Q000187:drug effects* / Q000502:physiology
chemical_list: C520305:Gper1 protein, rat; D043562:Receptors, G-Protein-Coupled; D017450:Receptors, Opioid, mu; D004958:Estradiol; C010452:estradiol-17 beta-benzoate
keywords: Arcuate nucleus of the hypothalamus; GPER; GPR30