{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T23:49:19Z","timestamp":1780789759824,"version":"3.54.1"},"reference-count":66,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:p>Prolactin (PRL), synthesized and secreted from lactotrophs of the anterior pituitary gland, is tonically inhibited by hypothalamic dopamine (DA) throughout the female reproductive (estrous) cycle. Our laboratory has shown that DA hyperpolarizes these cells by activating G protein-coupled inwardly rectifying K<jats:sup>+<\/jats:sup>(GIRK) channels; however, this response is only observed on proestrus. While the cellular mechanisms that allow for functional expression of this unique DA-signaling pathway are unclear, we hypothesized that activation of the DA-GIRK effector pathway is due to the rise in circulating estrogen (E<jats:sub>2<\/jats:sub>) during the preceding day of diestrus. Thus, we examined the effects of E<jats:sub>2<\/jats:sub>on primary lactotrophs isolated from female rats. Treatment with a physiological concentration of E<jats:sub>2<\/jats:sub>(40\u201380 pg\/ml, in vivo or in vitro) induced a proestrous phenotype in diestrous lactotrophs. These cells exhibited a DA-induced membrane hyperpolarization, as well as a secretory rebound of PRL following DA withdrawal (characteristic of proestrous cells). Internal dialysis of GTP\u03b3S demonstrated that E<jats:sub>2<\/jats:sub>exposure enabled functional expression of GIRK channels, and this regulation by E<jats:sub>2<\/jats:sub>did not involve the D<jats:sub>2<\/jats:sub>R. The effect of E<jats:sub>2<\/jats:sub>was blocked by the receptor antagonist, ICI 182,780, and by the protein synthesis inhibitor, cycloheximide. Single-cell analysis revealed increased mRNA expression of GIRK channel subunits in E<jats:sub>2<\/jats:sub>-treated lactotrophs. While E<jats:sub>2<\/jats:sub>is known to have multiple actions on the lactotroph, the present findings illuminate a novel action of E<jats:sub>2<\/jats:sub>in lactotrophs\u2014regulation of the expression of a DA effector, the GIRK channel.<\/jats:p>","DOI":"10.1152\/ajpregu.00138.2011","type":"journal-article","created":{"date-parts":[[2011,6,9]],"date-time":"2011-06-09T00:46:12Z","timestamp":1307580372000},"page":"R746-R756","source":"Crossref","is-referenced-by-count":13,"title":["Estrogen regulation of the dopamine-activated GIRK channel in pituitary lactotrophs: implications for regulation of prolactin release during the estrous cycle"],"prefix":"10.1152","volume":"301","author":[{"given":"Heather R.","family":"Christensen","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Physiological Science, St. Louis University, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Murawsky","sequence":"additional","affiliation":[{"name":"James L. 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