Dissertation/Thesis Abstract

Tamoxifen and ICI 182,780 activate GPER-1 in orphanin FQ neurons to facilitate sexual receptivity in female rats
by Long, Nathan P., M.S., California State University, Long Beach, 2016, 57; 10142967
Abstract (Summary)

Infusion of 17β-estradiol into the arcuate nucleus of the hypothalamus (ARH) 47.5 hours after estrogen benzoate (EB) priming rapidly facilitates sexual receptivity (lordosis) via G protein-coupled estrogen receptor 1 (GPER) that deactivates µ-opioid receptors (MOP) in the medial pre-optic nucleus of the hypothalamus (MPN). Initial estradiol inhibits lordosis via activating an ARH neurocircuit that activates MPN MOP, and simultaneously upregulates orphanin FQ/ nociception (OFQ/N), its cognate receptor (ORL-1), and progesterone receptor (PR) in the ARH. Subsequent ORL-1 activation 48 hours post-EB deactivates MPN MOP to facilitate lordosis. Thus, I hypothesized that GPER directly regulates OFQ/N neurons and tested whether EB increased coexpression of GPER and OFQ/N in ARH neurons. EB significantly increased the number of GPER OFQ/N expressing neurons. Antiestrogens, tamoxifen (TAM) and ICI 182,780 (ICI), are treatments for some estrogen responsive tumors, but sometimes exacerbate tumor proliferation via GPER. I hypothesized that TAM and ICI activate ARH GPER and facilitate lordosis via deactivation of MPN MOP. In EB-primed rats, ARH infusion of either TAM or ICI facilitated lordosis and deactivated MPN MOP. GPER antagonist, G15, blocked these results. Thus, TAM and ICI rapidly activate ARH GPER neurons that express OFQ/N to facilitate sexual receptivity.

Indexing (document details)
Advisor: Sinchak, Kevin
Commitee: Tsai, Houng-Wei, Young, Kelly
School: California State University, Long Beach
Department: Biological Sciences
School Location: United States -- California
Source: MAI 55/06M(E), Masters Abstracts International
Subjects: Neurosciences, Endocrinology
Keywords: Arcuate nucleus of the hypothalamus, Estradiol, G-protein coupled estrogen receptor, Lordosis, Tamoxifen
Publication Number: 10142967
ISBN: 978-1-339-98221-2
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