{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:48:48Z","timestamp":1787791728390,"version":"build-2784847793"},"reference-count":48,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11,1]]},"abstract":"<jats:p>Dopamine and estradiol interact in the regulation of lactotroph cell proliferation and prolactin secretion. Ablation of the dopamine D2 receptor gene (Drd2\u2212\/\u2212) in mice leads to a sexually dimorphic phenotype of hyperprolactinemia and pituitary hyperplasia, which is stronger in females. TGF-\u03b21 is a known inhibitor of lactotroph proliferation. TGF-\u03b21 is regulated by dopamine and estradiol, and it is usually down-regulated in prolactinoma experimental models. To understand the role of TGF-\u03b21 in the gender-specific development of prolactinomas in Drd2\u2212\/\u2212 mice, we compared the expression of different components of the pituitary TGF-\u03b21 system, including active cytokine content, latent TGF-\u03b2\u2013binding protein isoforms, and possible local TGF-\u03b21 activators, in males and females in this model. Furthermore, we evaluated the effects of dopamine and estradiol administration to elucidate their role in TGF-\u03b21 system regulation. The expression of active TGF-\u03b21, latent TGF-\u03b2\u2013binding protein isoforms, and several putative TGF-\u03b21 activators evaluated was higher in male than in female mouse pituitary glands. However, Drd2\u2212\/\u2212 female mice were more sensitive to the decrease in active TGF-\u03b21 content, as reflected by the down-regulation of TGF-\u03b21 target genes. Estrogen and dopamine caused differential regulation of several components of the TGF-\u03b21 system. In particular, we found sex- and genotype- dependent regulation of active TGF-\u03b21 content and a similar expression pattern for 2 of the putative TGF-\u03b21 activators, thrombospondin-1 and kallikrein-1, suggesting that these proteins could mediate TGF-\u03b21 activation elicited by dopamine and estradiol. Our results indicate that (1) the loss of dopaminergic tone affects the pituitary TGF-\u03b21 system more strongly in females than in males, (2) males express higher levels of pituitary TGF-\u03b21 system components including active cytokine, and (3) estradiol negatively controls most of the components of the system. Because TGF-\u03b21 inhibits lactotroph proliferation, we propose that the higher levels of the TGF-\u03b21 system in males could protect or delay the development of prolactinomas in Drd2\u2212\/\u2212 male mice.<\/jats:p>","DOI":"10.1210\/en.2013-1433","type":"journal-article","created":{"date-parts":[[2013,9,6]],"date-time":"2013-09-06T02:32:24Z","timestamp":1378434744000},"page":"4192-4205","source":"Crossref","is-referenced-by-count":20,"title":["Sex Differences in the Pituitary Transforming Growth Factor-\u03b21 System: Studies in a Model of Resistant Prolactinomas"],"prefix":"10.1210","volume":"154","author":[{"given":"M. Victoria","family":"Recouvreux","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental (M.V.R., L.L., M.A.C., M.C.G., A.O., 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":"Lara","family":"Lapyckyj","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental (M.V.R., L.L., M.A.C., M.C.G., A.O., 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. 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