{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:35:32Z","timestamp":1780572932930,"version":"3.54.1"},"reference-count":52,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"<jats:p>Sexual receptivity in the female rat is dependent on dose and duration of estradiol exposure. A 2 \u03bcg dose of estradiol benzoate (EB) primes reproductive behavior circuits without facilitating lordosis. However, 50 \u03bcg EB facilitates lordosis after 48 hours. Both EB doses activate membrane estrogen receptor-\u03b1 (mER\u03b1) that complexes with and signals through metabotropic glutamate receptor-1a (mGluR1a). This mER\u03b1-mGluR1a signaling activates a multisynaptic lordosis-inhibiting circuit in the arcuate nucleus (ARH) that releases \u03b2-endorphin in the medial preoptic nucleus (MPN), activating \u03bc-opioid receptors (MOP). MPN MOP activation is maintained, inhibiting lordosis for 48 hours by 2 \u03bcg EB, whereas 50 \u03bcg EB at 48 hours deactivates MPN MOP, facilitating lordosis. We hypothesized that 50 \u03bcg EB down-regulates ER\u03b1 and mER\u03b1-mGluR1a complexes in the ARH to remove mER\u03b1-mGluR1a signaling. In experiment I, 48 hours after 2 \u03bcg or 50 \u03bcg EB, the number of ARH ER\u03b1-immunopositive cells was reduced compared with controls. In experiment II, compared with oil controls, total ARH ER\u03b1 protein was decreased 48 hours after 50 \u03bcg EB, but the 2 \u03bcg dose was not. These results indicate that both EB doses reduced the total number of cells expressing ER\u03b1, but 2 \u03bcg EB may have maintained or increased ER\u03b1 expressed per cell, whereas 50 \u03bcg EB appeared to reduce total ER\u03b1 per cell. In experiment III, coimmunoprecipitation and Western blot revealed that total mER\u03b1 and coimmunoprecipitated mER\u03b1 with mGluR1a were greater 48 hours after 2 \u03bcg EB treatment vs rats receiving 50 \u03bcg EB. These results indicate 2 \u03bcg EB maintains but 50 \u03bcg EB down-regulates mER\u03b1-mGluR1a to regulate the lordosis circuit activity.<\/jats:p>","DOI":"10.1210\/en.2013-1235","type":"journal-article","created":{"date-parts":[[2013,7,4]],"date-time":"2013-07-04T08:13:43Z","timestamp":1372925623000},"page":"3251-3260","source":"Crossref","is-referenced-by-count":26,"title":["Estradiol Dose-Dependent Regulation of Membrane Estrogen Receptor-\u03b1, Metabotropic Glutamate Receptor-1a, and Their Complexes in the Arcuate Nucleus of the Hypothalamus in Female Rats"],"prefix":"10.1210","volume":"154","author":[{"given":"Matthew","family":"Mahavongtrakul","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, California State University, Long Beach, Long Beach, California 90840\u20139502"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha P.","family":"Kanjiya","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, 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