{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:21:04Z","timestamp":1784557264033,"version":"3.55.0"},"reference-count":45,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>\n                    Ovarian steroids control a variety of physiological functions. They exert actions through classical nuclear steroid receptors, but rapid non-genomic actions through specific membrane steroid receptors have been also described. In this study, we demonstrate that the G-protein-coupled estrogen receptor (GPER) is expressed in the rat pituitary gland and, at a high level, in the lactotroph population. Our results revealed that ~40% of the anterior pituitary cells are GPER positive and ~35% of the lactotrophs are GPER positive. By immunocytochemical and immuno-electron-microscopy studies, we demonstrated that GPER is localized in the plasmatic membrane but is also associated to the endoplasmic reticulum in rat lactotrophs. Moreover, we found that local\n                    <jats:italic>Gper<\/jats:italic>\n                    expression is regulated negatively by 17\u03b2-estradiol (E2) and progesterone (P4) and fluctuates during the estrus cycle, being minimal in proestrus. Interestingly, lack of ovarian steroids after an ovariectomy (OVX) significantly increased pituitary GPER expression specifically in the three morphologically different subtypes of lactotrophs. We found a rapid estradiol stimulatory effect on PRL secretion mediated by GPER, both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    , using a GPER agonist G1, and this effect was prevented by the GPER antagonist G36, demonstrating a novel role for this receptor. Then, the increased pituitary GPER expression after OVX could lead to alterations in the pituitary function as all three lactotroph subtypes are target of GPER ligand and could be involved in the PRL secretion mediated by GPER. Therefore, it should be taken into consideration in the response of the gland to an eventual hormone replacement therapy.\n                  <\/jats:p>","DOI":"10.1530\/joe-18-0402","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T13:19:36Z","timestamp":1540473576000},"page":"99-110","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":20,"title":["Role of GPER in the anterior pituitary gland focusing on lactotroph function"],"prefix":"10.1530","volume":"240","author":[{"given":"Mar\u00eda Andrea","family":"Camilletti","sequence":"first","affiliation":[{"name":"1Instituto de Biolog\u00eda y Medicina Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Abeledo-Machado","sequence":"additional","affiliation":[{"name":"1Instituto de Biolog\u00eda y Medicina Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimena","family":"Ferraris","sequence":"additional","affiliation":[{"name":"2Instituto de Investigaciones Biom\u00e9dicas, Facultad de Medicina, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo A","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"3Centro de Microscopia Electr\u00f3nica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Medicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika Y","family":"Faraoni","sequence":"additional","affiliation":[{"name":"1Instituto de Biolog\u00eda y Medicina Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Pisera","sequence":"additional","affiliation":[{"name":"2Instituto de Investigaciones Biom\u00e9dicas, Facultad de Medicina, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvina","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"3Centro de Microscopia Electr\u00f3nica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Medicas, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciela","family":"D\u00edaz-Torga","sequence":"additional","affiliation":[{"name":"1Instituto de Biolog\u00eda y Medicina Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref271","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nrendo.2011.122","article-title":"The G-protein-coupled estrogen receptor GPER in health and disease.","volume":"7","year":"2011","journal-title":"Nature Reviews Endocrinology"},{"key":"ref421","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/onc.2010.458","article-title":"A positive feedback loop of ER-alpha36\/EGFR promotes malignant growth of ER-negative breast cancer cells","volume":"30","year":"2011","journal-title":"Oncogene"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1210\/mend.16.1.0758","article-title":"Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis","volume":"16","year":"2002","journal-title":"Molecular Endocrinology"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1097\/gme.0b013e31825a27ab","article-title":"Oophorectomy: the debate between ovarian conservation and elective oophorectomy","volume":"20","year":"2013","journal-title":"Menopause"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/0304-3940(90)90173-7","article-title":"Evidence for a relationship between lactotroph heterogeneity and physiological context","volume":"120","year":"1990","journal-title":"Neurosciences Letters"},{"key":"ref431","first-page":"2057","article-title":"Involvement of ER-alpha36, Src, EGFR and STAT5 in the biphasic estrogen signaling of ER-negative breast cancer cells","volume":"27","year":"2012","journal-title":"Oncology Reports"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.1096\/fj.08-107672","article-title":"Nongenomic actions of estradiol compared with estrone and estriol in pituitary tumor cell signaling and proliferation","volume":"22","year":"2008","journal-title":"FASEB Journal"},{"key":"ref291","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1126\/science.1106943","article-title":"A transmembrane intracellular estrogen receptor mediates rapid cell signaling","volume":"307","year":"2005","journal-title":"Science"},{"key":"ref341","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1083\/jcb.47.1.61","article-title":"Production of both prolactin and growth hormone by clonal strains of rat pituitary tumor cells. Differential effects of hydrocortisone and tissue extracts","volume":"47","year":"1970","journal-title":"Journal of Cell Biology"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.jsbmb.2015.06.014","article-title":"What have we learned about GPER function in physiology and disease from knockout mice?","volume":"153","year":"2015","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref311","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.anireprosci.2013.04.003","article-title":"Expression of estradiol receptor, GPR30, in bovine anterior pituitary and effects of GPR30 agonist on GnRH-induced LH secretion","volume":"139","year":"2013","journal-title":"Animal Reproduction Science"},{"key":"ref321","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1111\/j.1365-2826.2010.02010.x","article-title":"Cell life and death in the anterior pituitary gland: role of oestrogens","volume":"22","year":"2010","journal-title":"Journal of Neuroendocrinology"},{"key":"ref401","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1152\/ajpendo.90785.2008","article-title":"Estrogens exert a rapid apoptotic action in anterior pituitary cells of : and https org","year":"2009","journal-title":"American Journal Physiology Endocrinology Metabolism"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"e97383","DOI":"10.1371\/journal.pone.0097383","article-title":"Prolactin induces apoptosis of lactotropes in female rodents","volume":"9","year":"2014","journal-title":"PLoS ONE"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jsbmb.2017.05.006","article-title":"Role of GPER in estrogen-dependent nitric oxide formation and vasodilation","volume":"176","year":"2018","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref221","first-page":"83","article-title":"Occurrence of atypical lactotrophs associated with levels of prolactin secretory activity","volume":"18","year":"1994","journal-title":"Biocell"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1530\/JOE-16-0371","article-title":"Sex differences in the development of prolactinoma in mice overexpressing hCGbeta: role of TGFbeta1","volume":"232","year":"2017","journal-title":"Journal of Endocrinology"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.steroids.2008.01.002","article-title":"Estradiol interacts with insulin through membrane receptors to induce an antimitogenic effect on lactotroph cells","volume":"73","year":"2008","journal-title":"Steroids"},{"key":"ref301","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1021\/cb700072n","article-title":"Synthetic estrogen derivatives demonstrate the functionality of intracellular GPR30","volume":"2","year":"2007","journal-title":"ACS Chemical Biology"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"3976","DOI":"10.1210\/endo.139.9.6181","article-title":"Cellular distribution and gene regulation of estrogen receptors alpha and beta in the rat pituitary gland","volume":"139","year":"1998","journal-title":"Endocrinology"},{"key":"ref211","first-page":"105","article-title":"The unfolding stories of GPR30, a new membrane-bound estrogen receptor","volume":"204","year":"2010","journal-title":"Journal of Endocrinology"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1111\/j.1365-2826.2009.01893.x","article-title":"GPR30 differentially regulates short latency responses of luteinising hormone and prolactin secretion to oestradiol","volume":"21","year":"2009","journal-title":"Journal of Neuroendocrinology"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.mce.2015.08.009","article-title":"Inhibitory role of ERbeta on anterior pituitary cell proliferation by controlling the expression of proteins related to cell cycle progression","volume":"415","year":"2015","journal-title":"Molecular and Cellular Endocrinology"},{"key":"ref411","doi-asserted-by":"crossref","first-page":"e41299","DOI":"10.1371\/journal.pone.0041299","article-title":"Estrogens induce expression of membrane-associated estrogen receptor alpha isoforms in lactotropes","volume":"7","year":"2012","journal-title":"PLoS ONE"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1677\/JOE-09-0066","article-title":"Localisation of GPR30, a novel G protein-coupled oestrogen receptor, suggests multiple functions in rodent brain and peripheral tissues","volume":"202","year":"2009","journal-title":"Journal of Endocrinology"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1679\/aohc.50.455","article-title":"Changing ultrastructures in the estrous cycle and postnatal development of prolactin cells in the rat anterior pituitary as studied by immunogold electron microscopy","volume":"50","year":"1987","journal-title":"Archivum Histologicum Japonicum"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jsbmb.2016.12.005","article-title":"Role of G-protein-coupled estrogen receptor (GPER\/GPR30) in maintenance of meiotic arrest in fish oocytes","volume":"167","year":"2017","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref441","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1042\/CS20160114","article-title":"GPER-novel membrane oestrogen receptor","volume":"130","year":"2016","journal-title":"Clinical Science"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"E2713","DOI":"10.3390\/ijms18122713","article-title":"G protein-coupled receptors at the crossroad between physiologic and pathologic angiogenesis: old paradigms and emerging concepts","volume":"18","year":"2017","journal-title":"International Journal of Molecular Sciences"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1210\/en.2008-0623","article-title":"Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice","volume":"150","year":"2009","journal-title":"Endocrinology"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.tins.2017.09.001","article-title":"Estradiol membrane-initiated signaling in the brain mediates reproduction","volume":"40","year":"2017","journal-title":"Trends in Neurosciences"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.brainresbull.2007.03.001","article-title":"Prolactin secretory surge during estrus coincides with increased dopamine activity in the hypothalamus and preoptic area and is not altered by ovariectomy on proestrus","volume":"73","year":"2007","journal-title":"Brain Research Bulletin"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1677\/JOE-07-0017","article-title":"Distribution and characterization of estrogen receptor G protein-coupled receptor 30 in the rat central nervous system","volume":"193","year":"2007","journal-title":"Journal of Endocrinology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/j.1365-2826.2007.01567.x","article-title":"Thyrotrophin-releasing hormone, vasoactive intestinal peptide, prolactin-releasing peptide and dopamine regulation of prolactin secretion by different lactotroph morphological subtypes in the rat","volume":"19","year":"2007","journal-title":"Journal of Neuroendocrinology"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1210\/en.2008-1759","article-title":"G protein-coupled receptor 30: estrogen receptor or collaborator?","volume":"150","year":"2009","journal-title":"Endocrinology"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1210\/en.2008-0756","article-title":"Estrogen receptor-alpha mediates the epidermal growth factor-stimulated prolactin expression and release in lactotrophs","volume":"150","year":"2009","journal-title":"Endocrinology"},{"key":"ref371","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1289\/ehp.1205826","article-title":"Bisphenol S disrupts estradiol-induced nongenomic signaling in a rat pituitary cell line: effects on cell functions","volume":"121","year":"2013","journal-title":"Environmental Health Perspectives"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nrm.2016.122","article-title":"Nuclear receptors outside the nucleus: extranuclear signalling by steroid receptors","volume":"17","year":"2016","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.steroids.2007.12.025","article-title":"Association of the membrane estrogen receptor, GPR30, with breast tumor metastasis and transactivation of the epidermal growth factor receptor","volume":"73","year":"2008","journal-title":"Steroids"},{"key":"ref391","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1172\/JCI107600","article-title":"Augmentation of prolactin secretion by estrogen in hypogonadal women","volume":"53","year":"1974","journal-title":"Journal of Clinical Investigation"},{"key":"ref121","first-page":"2323","article-title":"The ovarian cycle of the rat","year":"1986","journal-title":"The Physiology of Reproduction"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1210\/mend.14.10.0532","article-title":"Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF","volume":"14","year":"2000","journal-title":"Molecular Endocrinology"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S1043-2760(01)00377-0","article-title":"Rapid actions of plasma membrane estrogen receptors","volume":"12","year":"2001","journal-title":"Trends in Endocrinology and Metabolism"},{"key":"ref361","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1210\/en.2004-1064","article-title":"Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells","volume":"146","year":"2005","journal-title":"Endocrinology"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0065-1281(97)80022-0","article-title":"Heterogeneity of pituitary lactotrophs: immunocytochemical identification of functional subtypes","volume":"99","year":"1997","journal-title":"Acta Histochemica"}],"container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/240\/2\/JOE-18-0402.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/240\/2\/JOE-18-0402.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:56:28Z","timestamp":1784555788000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/240\/2\/99-110\/5140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2]]},"references-count":45,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/joe-18-0402","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2]]}}}