{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:48:42Z","timestamp":1787791722942,"version":"build-2784847793"},"reference-count":45,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:p>\n                    Female transgenic mice that overexpress the human chorionic gonadotrophin \u03b2 subunit (hCG\u03b2+) develop prolactinomas, whereas hCG\u03b2+ males do not. The high levels of circulating hCG induce massive luteinization in the ovary of hCG\u03b2+ females, and progesterone becomes the primary steroid hormone produced, but estradiol remains at physiological level. The involvement of high levels of progesterone in lactotroph proliferation is not clearly understood; hence, the pathogenesis of prolactinomas in hCG\u03b2+ females remains unclear. TGF\u03b21 is an inhibitor of lactotroph function, and the reduced TGF\u03b21 activity found in prolactinomas has been proposed to be involved in tumor development. The aim of the present work was to study the role of TGF\u03b21 in the gender-specific development of prolactinomas in hCG\u03b2+ mice. We compared the expression of different components of the pituitary TGF\u03b21 system in males and females in this model. We found reduced TGF\u03b21 levels, reduced expression of TGF\u03b21 target genes, TGF\u03b21 receptors,\n                    <jats:italic>Ltbp1<\/jats:italic>\n                    ,\n                    <jats:italic>Smad4<\/jats:italic>\n                    and\n                    <jats:italic>Smad7<\/jats:italic>\n                    in hCG\u03b2+ female pituitaries. However, no differences were found between the transgenic and wild-type male pituitaries. We postulate that decreased pituitary TGF\u03b21 activity in hCG\u03b2+ females is involved in the development of prolactinomas. In fact, we demonstrated that an\n                    <jats:italic>in vivo<\/jats:italic>\n                    treatment carried out for increasing pituitary TGF\u03b21 activity, was successful in reducing the prolactinoma development, and the hyperprolactinemia in hCG\u03b2+ females. Moreover, the stronger TGF\u03b21 system found in males could protect them from excessive lactotroph proliferation. Sex differences in the regulation of the pituitary TGF\u03b21 system could explain gender differences in the incidence of prolactinoma.\n                  <\/jats:p>","DOI":"10.1530\/joe-16-0371","type":"journal-article","created":{"date-parts":[[2017,1,17]],"date-time":"2017-01-17T20:40:58Z","timestamp":1484685658000},"page":"535-546","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":21,"title":["Sex differences in the development of prolactinoma in mice overexpressing hCG\u03b2: role of TGF\u03b21"],"prefix":"10.1530","volume":"232","author":[{"given":"Erika Y","family":"Faraoni","sequence":"first","affiliation":[{"name":"1Instituto de Biolog\u00eda y Medicina ExperimentalConsejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Andrea","family":"Camilletti","sequence":"additional","affiliation":[{"name":"1Instituto de Biolog\u00eda y Medicina ExperimentalConsejo 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 ExperimentalConsejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura D","family":"Ratner","sequence":"additional","affiliation":[{"name":"1Instituto de Biolog\u00eda y Medicina ExperimentalConsejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"De Fino","sequence":"additional","affiliation":[{"name":"2Instituto de Investigaciones Farmacol\u00f3gicasConsejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilpo","family":"Huhtaniemi","sequence":"additional","affiliation":[{"name":"3Department of Surgery & CancerInstitute of Reproductive and Developmental Biology, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana B","family":"Rulli","sequence":"additional","affiliation":[{"name":"1Instituto de Biolog\u00eda y Medicina ExperimentalConsejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciela","family":"D\u00edaz-Torga","sequence":"additional","affiliation":[{"name":"1Instituto de Biolog\u00eda y Medicina ExperimentalConsejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2017021017102683000_232.3.535.1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208893"},{"key":"2017021017102683000_232.3.535.2","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-10-0016"},{"key":"2017021017102683000_232.3.535.3","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1159\/000126583","article-title":"Progesterone reverses the estradiol-induced decrease in tyrosine hydroxylase mRNA levels in the arcuate nucleus","volume":"58","author":"Arbogast","year":"1993","journal-title":"Neuroendocrinology"},{"key":"2017021017102683000_232.3.535.4","doi-asserted-by":"publisher","DOI":"10.1210\/en.135.1.343"},{"key":"2017021017102683000_232.3.535.5","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-6-4-564"},{"key":"2017021017102683000_232.3.535.6","doi-asserted-by":"publisher","DOI":"10.1210\/er.22.6.724"},{"key":"2017021017102683000_232.3.535.7","first-page":"1568","article-title":"PMEPA1, a transforming growth factor-beta-induced marker of terminal colonocyte differentiation whose expression is maintained in primary and metastatic colon cancer","volume":"63","author":"Brunschwig","year":"2003","journal-title":"Cancer Research"},{"key":"2017021017102683000_232.3.535.8","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1480325"},{"key":"2017021017102683000_232.3.535.9","doi-asserted-by":"crossref","first-page":"6815","DOI":"10.1016\/S0021-9258(17)37449-5","article-title":"Characterization and autoregulation of latent transforming growth factor beta (TGF beta) complexes in osteoblast-like cell lines. 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