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Estrogen receptor‐α is required for estrogen‐induced μ‐opioid receptor internalization
Author(s) -
Micevych Paul E,
Rissman Emilie F.,
Gustafsson JanÅke,
Sinchak Kevin
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10526
Subject(s) - estrogen receptor , estrogen , internalization , endocrinology , medicine , estrogen receptor beta , endogenous opioid , estrogen receptor alpha , ovariectomized rat , estrogen related receptor alpha , lordosis behavior , opioid receptor , chemistry , agonist , receptor , biology , opioid , estradiol benzoate , cancer , breast cancer
Endogenous opioid circuits are pivotal for the regulation of sexual receptivity. Treatment of mice with morphine, a preferential μ‐opioid receptor (MOR) agonist, severely attenuates lordosis. Estrogen induces internalization of MOR in cell groups of the limbic‐hypothalamic lordosis‐regulating circuit. Because rapid MOR internalization is mediated by estrogen release of endogenous opioid peptides, internalization has been used as a neurochemical signature of estrogen action in the central nervous system. Together these results indicate that estrogen induces a MOR mediated inhibition of sexual receptivity. To determine which estrogen receptor, estrogen receptor‐α (ERα) or estrogen receptor‐β (ERβ), mediates MOR internalization, ERα knockout (ERαKO), ERβ knockout (ERβKO) and wild‐type (WT) mice were used in the present study. WT, ERαKO and ERβKO mice had similar MOR distributions in the limbic‐hypothalamic lordosis‐regulating circuit. Estrogen treatment internalized MOR in the medial preoptic nucleus of ovariectomized WT and ERβKO, but not ERαKO mice. Treatment of ERαKO mice with the selective endogenous MOR ligand, endomorphin‐1, induced levels of MOR internalization similar to WT mice suggesting that MOR in ERαKO mice could be activated and were probably functional. The results of the present experiments indicate that ERα is required for estrogen‐induced MOR internalization and suggest that ERα can mediate rapid actions of estrogen. © 2002 Wiley‐Liss, Inc.