Plasma membrane G protein-coupled estrogen receptor 1 (GPER) mediates rapid estradiol facilitation of sexual receptivity through the orphanin-FQ-ORL-1 system in estradiol primed female rats.

Abstract

In estradiol-primed nonreceptive ovariectomized rats, activation of G protein-coupled estrogen receptor 1 (GPER) in the arcuate nucleus of the hypothalamus (ARH) rapidly facilitates sexual receptivity (lordosis). Estradiol priming activates ARH β-endorphin (β-END) neurons that then activate medial preoptic (MPN) μ-opioid receptors (MOP) to inhibit lordosis. ARH infusion of non-esterified 17β-estradiol (E2) 47.5 h after 17β-estradiol benzoate (2 μg EB) priming deactivates MPN MOP and rapidly facilitates lordosis within 30 min via activation of GPER. Since it was unclear where GPERs were located in the neuron, we tested the hypothesis that GPER signaling is initiated at the plasma membrane. Membrane impermeable estradiol (17β-estradiol conjugated to biotin; E-Biotin) infused into the ARH of EB primed rats facilitated lordosis within 30 min, and MPN MOP was deactivated. These actions were blocked by pretreating with GPER antagonist, G-15. Further, we used cell fractionation and western blot techniques to demonstrate that GPER is expressed both in plasma membrane and cytosolic ARH fractions. In previous studies, the orphanin FQ/nociceptin-opioid receptor-like receptor-1 (OFQ/N-ORL-1) system mediated estradiol-only facilitation of lordosis. Therefore, we tested whether the OFQ/N-ORL-1 system mediates E-Biotin-GPER facilitation of lordosis. Pretreatment of UFP-101, an ORL-1 selective antagonist, blocked the facilitation of lordosis and deactivation of MPN MOP by ARH infusion of E-Biotin. Double-label immunohistochemistry revealed that GPER is expressed within approximately 70% of OFQ/N neurons. These data indicate that membrane GPER mediates the E2/E-Biotin facilitation of lordosis by inducing OFQ/N neurotransmission, which inhibits β-END neurotransmission to reduce MPN MOP activation.

• Authors: Reema Tominna, Sima Chokr, Micah Feri, Timbora Chuon, Kevin Sinchak
• Journal: Hormones and behavior (Horm Behav) Vol. 112 Pg. 89-99 (06 2019) ISSN: 1095-6867 [Electronic] United States
• PMID: 30981690 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Gper1 protein, rat
• Opioid Peptides
• Receptors, G-Protein-Coupled
• Receptors, Opioid
• Estradiol
• Nociceptin Receptor
• Oprl protein, rat

Topics

• Animals
• Estradiol (metabolism, pharmacology)
• Female
• Hypothalamus (drug effects, metabolism)
• Male
• Neurons (drug effects, metabolism)
• Opioid Peptides (metabolism)
• Posture (physiology)
• Rats
• Rats, Long-Evans
• Receptors, G-Protein-Coupled (physiology)
• Receptors, Opioid (metabolism)
• Sexual Behavior, Animal (drug effects, physiology)
• Signal Transduction (drug effects)
• Nociceptin Receptor
• Nociceptin