{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:35:38Z","timestamp":1790865338791,"version":"4.1.0"},"reference-count":29,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,7,1]]},"abstract":"<jats:p>Dopamine, acting through the dopamine type 2 receptor (Drd2), is the main inhibitor of pituitary prolactin (PRL) secretion and lactotroph proliferation. TGF-\u03b21 is involved, at least in part, in mediating these actions. It was described that TGF-\u03b21 synthesis in rat pituitary lactotrophs is up-regulated by dopamine and down-regulated by estradiol. TGF-\u03b21 is secreted as a large latent complex. The local regulation of cytokine activation in the pituitary has not yet been explored. In this work, we studied pituitary active and total TGF-\u03b21 content, as well as TGF-\u03b21 mRNA, and the in vivo role of dopamine and estradiol on pituitary TGF-\u03b21 levels. Adult female mice (wild type), and female mice with a null mutation in the Drd2 (Drd2\u2212\/\u2212), were used. The loss of dopaminergic tone induced a decrease in TGF-\u03b21 mRNA expression, in active and total cytokine content, and in TGF-\u03b2 type II receptor expression. Dopamine regulation of pituitary TGF-\u03b21 activation process was inferred by the inhibition of active cytokine by in vivo sulpiride treatment. Interestingly, in the absence of dopaminergic tone, estradiol induced a strong increase in active TGF-\u03b21. PRL secretion correlated with active, but not total cytokine. TGF-\u03b21 inhibitory action on lactotroph proliferation and PRL secretion was decreased in Drd2\u2212\/\u2212 pituitary cells, in correlation with decreased TGF-\u03b2 type II receptor. The study of the TGF-\u03b21 activation process and its regulation is essential to understand the cytokine activity. As an intermediary of dopamine inhibition of lactotroph function, TGF-\u03b21 and local activators may be important targets in the treatment of dopamine agonist-resistant prolactinomas.<\/jats:p>","DOI":"10.1210\/en.2010-1464","type":"journal-article","created":{"date-parts":[[2011,4,27]],"date-time":"2011-04-27T00:35:38Z","timestamp":1303864538000},"page":"2722-2730","source":"Crossref","is-referenced-by-count":28,"title":["Active and Total Transforming Growth Factor-\u03b21 Are Differentially Regulated by Dopamine and Estradiol in the Pituitary"],"prefix":"10.1210","volume":"152","author":[{"given":"M. Victoria","family":"Recouvreux","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental (M.V.R., M.C.G., D.B.-V., G.D.-T.), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires 1428, Argentina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Clara","family":"Guida","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental (M.V.R., M.C.G., D.B.-V., G.D.-T.), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires 1428, Argentina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Rifkin","sequence":"first","affiliation":[{"name":"Department of Cell Biology (D.B.R.), New York University Medical Center, New York, New York 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damasia","family":"Becu-Villalobos","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental (M.V.R., M.C.G., D.B.-V., G.D.-T.), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires 1428, Argentina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciela","family":"D\u00edaz-Torga","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental (M.V.R., M.C.G., D.B.-V., G.D.-T.), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires 1428, Argentina;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2011,4,26]]},"reference":[{"key":"2020071612370394600_B1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1210\/edrv-6-4-564","article-title":"Dopamine: a prolactin inhibiting hormone.","volume":"6","author":"Ben-Jonathan","year":"1985","journal-title":"Endocr Rev"},{"key":"2020071612370394600_B2","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1210\/edrv.22.6.0451","article-title":"Dopamine as a prolactin (PRL) inhibitor.","volume":"22","author":"Ben-Jonathan","year":"2001","journal-title":"Endocr Rev"},{"key":"2020071612370394600_B3","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1152\/physrev.1998.78.1.189","article-title":"Dopamine receptors: from structure to function.","volume":"78","author":"Missale","year":"1998","journal-title":"Physiol Rev"},{"key":"2020071612370394600_B4","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1210\/endo.143.4.8750","article-title":"Disruption of the D2 dopamine receptor alters GH and IGF-I secretion and causes dwarfism in male mice.","volume":"143","author":"D\u00edaz-Torga","year":"2002","journal-title":"Endocrinology"},{"key":"2020071612370394600_B5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0896-6273(00)80351-7","article-title":"Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice.","volume":"19","author":"Kelly","year":"1997","journal-title":"Neuron"},{"key":"2020071612370394600_B6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1159\/000094308","article-title":"The dopaminergic D2 receptor knockout mouse: an animal model of prolactinoma.","volume":"35","author":"Cristina","year":"2006","journal-title":"Front Horm Res"},{"key":"2020071612370394600_B7","doi-asserted-by":"crossref","first-page":"18758","DOI":"10.1073\/pnas.0805411105","article-title":"Perturbation of transforming growth factor (TGF)-\u03b21 association with latent TGF-\u03b2 binding protein yields inflammation and tumors.","volume":"105","author":"Yoshinaga","year":"2008","journal-title":"Proc Natil Acad Sci USA"},{"key":"2020071612370394600_B8","first-page":"1825","article-title":"Transforming growth factor-\u03b21 messenger RNA and protein expression in the pituitary gland: its action on prolactin secretion and lactotropic growth.","volume":"6","author":"Sarkar","year":"1992","journal-title":"Mol Endocrinol"},{"key":"2020071612370394600_B9","doi-asserted-by":"crossref","first-page":"3620","DOI":"10.1210\/endo.139.8.6135","article-title":"Role of transforming growth factor-b type I and TGF-b type II receptores in the TGF-b1 regulated gene expression in pituitary prolactin-secreting lactotropes.","volume":"139","author":"Sarkar","year":"1998","journal-title":"Endocrinology"},{"key":"2020071612370394600_B10","doi-asserted-by":"crossref","first-page":"4179","DOI":"10.1210\/en.2005-0430","article-title":"Dopamine, dopamine D2 receptor short isoform, transforming growth factor (TGF)-\u03b21, and TGF-\u03b2 type II receptor interact to inhibit the growth of pituitary lactotropes.","volume":"146","author":"Sarkar","year":"2005","journal-title":"Endocrinology"},{"key":"2020071612370394600_B11","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1111\/j.1530-0277.2007.00539.x","article-title":"Ethanol alters production and secretion of estrogen-regulated growth factors that control prolactin-secreting tumors in the pituitary.","volume":"31","author":"Sarkar","year":"2007","journal-title":"Alcohol Clin Exp Res"},{"key":"2020071612370394600_B12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1677\/joe.0.1490019","article-title":"Pituitary lactotrope expresses transforming growth factor b (TGF-b) type II receptor mRNA and protein and contains I-TGF-b1 binding sites.","volume":"149","author":"De","year":"1996","journal-title":"J Endocrinol"},{"key":"2020071612370394600_B13","first-page":"4892","article-title":"Reduction in the expression and action of transforming growth factor-b1 on lactotropes during estrogen-induced tumorigenesis.","volume":"55","author":"Pastorcic","year":"1995","journal-title":"Cancer Res"},{"key":"2020071612370394600_B14","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1210\/endo.142.5.8117","article-title":"Analysis of homogeneous populations of anterior pituitary folliculostellate cells by laser capture microdissection and reverse transcription-polymerase chain reaction.","volume":"142","author":"Jin","year":"2001","journal-title":"Endocrinology"},{"key":"2020071612370394600_B15","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1242\/jcs.00229","article-title":"Making sense of latent TGF\u03b2 activation.","volume":"116","author":"Annes","year":"2003","journal-title":"J Cell Sci"},{"key":"2020071612370394600_B16","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1083\/jcb.200312172","article-title":"Integrin \u03b1V\u03b26-mediated activation of latent TGF-\u03b2 requires the latent TGF-\u03b2 binding protein-1.","volume":"165","author":"Annes","year":"2004","journal-title":"J Cell Biol"},{"key":"2020071612370394600_B17","doi-asserted-by":"crossref","first-page":"5348","DOI":"10.1210\/endo.140.11.7118","article-title":"Pituitary lactotroph adenomas develop after prolonged lactotroph hyperplasia in dopamine D2 receptor-deficient mice.","volume":"140","author":"Asa","year":"1999","journal-title":"Endocrinology"},{"key":"2020071612370394600_B18","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1159\/000094307","article-title":"Genesis of prolactinomas: studies using estrogen-treated animals.","volume":"35","author":"Sarkar","year":"2006","journal-title":"Front Horm Res"},{"key":"2020071612370394600_B19","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0303-7207(00)00270-7","article-title":"Bromocriptine restores Angiotensin II response in pituitary hyperplasia.","volume":"165","author":"Gonz\u00e1lez Iglesias","year":"2000","journal-title":"Mol Cell Endocrinol"},{"key":"2020071612370394600_B20","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1210\/en.2004-1445","article-title":"Increased pituitary vascular endothelial growth factor-A in dopaminergic D2 receptor knockout female mice.","volume":"146","author":"Cristina","year":"2005","journal-title":"Endocrinology"},{"key":"2020071612370394600_B21","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1210\/en.2005-0893","article-title":"Dopamine and transforming growth factor-\u03b21: an odd couple in growth inhibition of the lactotrophs.","volume":"146","author":"Ben-Jonathan","year":"2005","journal-title":"Endocrinology"},{"key":"2020071612370394600_B22","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/ki.1997.188","article-title":"Latent transforming growth factor-\u03b2: structural features and mechanisms of activation.","volume":"51","author":"Munger","year":"1997","journal-title":"Kidney Int"},{"key":"2020071612370394600_B23","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1097\/00003081-198012000-00008","article-title":"Lactation suppression.","volume":"23","author":"Kochenour","year":"1980","journal-title":"Clin Obstet Gynecol"},{"key":"2020071612370394600_B24","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1136\/bmj.4.5627.387","article-title":"Inhibition of lactation by oestrogens.","volume":"4","author":"Llewellyn-Jones","year":"1968","journal-title":"Br Med J"},{"key":"2020071612370394600_B25","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1210\/endo.141.3.7382","article-title":"Transforming growth factor-b3 stimulates lactotrope cell growth by increasing basic fibroblast growth factor from folliculo-stellate cells.","volume":"141","author":"Hentges","year":"2000","journal-title":"Endocrinology"},{"key":"2020071612370394600_B26","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1126\/science.285.5431.1259","article-title":"Genetic variation in susceptibility to endocrine disruption by estrogen in mice.","volume":"285","author":"Spearow","year":"1999","journal-title":"Science"},{"key":"2020071612370394600_B27","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1590\/S0100-879X2005001000005","article-title":"Regulation of pituitary hormones and cell proliferation by components of the extracellular matrix.","volume":"38","author":"Paez-Pereda","year":"2005","journal-title":"Braz J Med Biol Res"},{"key":"2020071612370394600_B28","doi-asserted-by":"crossref","first-page":"26775","DOI":"10.1016\/S0021-9258(18)47086-X","article-title":"Thrombospondin binds and activates the small and large forms of latent transforming growth factor-\u03b2 in a chemically defined system.","volume":"269","author":"Schultz-Cherry","year":"1994","journal-title":"J Biol Chem"},{"key":"2020071612370394600_B29","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1677\/joe.1.06925","article-title":"Changes in thrombospondin-1 levels in the endothelial cells of the anterior pituitary during estrogen-induced prolactin-secreting pituitary tumors.","volume":"192","author":"Sarkar","year":"2007","journal-title":"J Endocrinol"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/152\/7\/2722\/9038876\/endo2722.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/152\/7\/2722\/9038876\/endo2722.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T07:22:08Z","timestamp":1637565728000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/152\/7\/2722\/2457186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,4,26]]},"references-count":29,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2011,7,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2010-1464","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,4,26]]}}}