{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:55:16Z","timestamp":1790240116942,"version":"4.1.0"},"reference-count":59,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,1,1]]},"abstract":"<jats:p>Leptin, the 16,000 molecular weight protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta, in which it was found to be expressed. In the present work, we have found that recombinant human chorionic gonadotropin (hCG) added to BeWo choriocarcinoma cell line showed a stimulatory effect on endogenous leptin expression, when analyzed by Western blot. This effect was time and dose dependent. Maximal effect was achieved at hCG 100 IU\/ml. Moreover, hCG treatment enhanced leptin promoter activity up to 12.9 times, evaluated by transient transfection with a plasmid construction containing different promoter regions and the reporter gene luciferase. This effect was dose dependent and evidenced with all the promoter regions analyzed, regardless of length. Similar results were obtained with placental explants, thus indicating physiological relevance. Because hCG signal transduction usually involves cAMP signaling, this pathway was analyzed. Contrarily, we found that dibutyryl cAMP counteracted hCG effect on leptin expression. Furthermore, cotransfection with the catalytic subunit of PKA and\/or the transcription factor cAMP response element binding protein repressed leptin expression. Thereafter we determined that hCG effect could be partially blocked by pharmacologic inhibition of MAPK pathway with 50 \u03bcM PD98059 but not by the inhibition of the phosphatidylinositol 3-kinase pathway with 0.1 \u03bcm wortmannin. Moreover, hCG treatment promoted MAPK kinase and ERK1\/ERK2 phosphorylation in placental cells. Finally, cotransfection with a dominant-negative mutant of MAPK blocked the hCG-mediated activation of leptin expression. In conclusion, we provide some evidence suggesting that hCG induces leptin expression in trophoblastic cells probably involving the MAPK signal transduction pathway.<\/jats:p><jats:p>Human chorionic gonadotropin induces leptin expression in trophoblastic BeWo cells and placental explants analyzed by western-blot and reporter gene strategy. This effect involves the MAPK signal transduction pathway.<\/jats:p>","DOI":"10.1210\/en.2008-0522","type":"journal-article","created":{"date-parts":[[2008,9,12]],"date-time":"2008-09-12T00:44:51Z","timestamp":1221180291000},"page":"304-313","source":"Crossref","is-referenced-by-count":50,"title":["Up-Regulation of Placental Leptin by Human Chorionic Gonadotropin"],"prefix":"10.1210","volume":"150","author":[{"given":"Julieta L.","family":"Maymo\u0301","sequence":"first","affiliation":[{"name":"Departamento de Qui\u0301mica Biolo\u0301gica (J.L.M., J.C.C., C.L.V.), 1428 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pe\u0301rez Pe\u0301rez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqui\u0301mica Me\u0301dica y Biologi\u0301a Molecular (A.P.P., V.S.-M.), Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vi\u0301ctor","family":"Sa\u0301nchez-Margalet","sequence":"additional","affiliation":[{"name":"Departamento de Bioqui\u0301mica Me\u0301dica y Biologi\u0301a Molecular (A.P.P., V.S.-M.), Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u0301 L.","family":"Duen\u0303as","sequence":"additional","affiliation":[{"name":"Servicio de Ginecologi\u0301a y Obstetricia (J.L.D.), Hospital Universitario Virgen Macarena, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Calvo","sequence":"additional","affiliation":[{"name":"Departamento de Qui\u0301mica Biolo\u0301gica (J.L.M., J.C.C., C.L.V.), 1428 Buenos Aires, Argentina"},{"name":"Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Instituto de Biologi\u0301a y Medicina Experimental (J.C.C.), 1428 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia L.","family":"Varone","sequence":"additional","affiliation":[{"name":"Departamento de Qui\u0301mica Biolo\u0301gica (J.L.M., J.C.C., C.L.V.), 1428 Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2008,9,11]]},"reference":[{"key":"2020071613564225300_R1","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1210\/jc.2003-032127","article-title":"The leptin system during human endometrial receptivity and preimplantation development.","volume":"89","author":"Cervero","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613564225300_R2","first-page":"31","article-title":"Cytokines in implantation.","volume":"55","author":"Kauma","year":"2000","journal-title":"J Reprod Fertil Suppl"},{"key":"2020071613564225300_R3","first-page":"181","article-title":"Signal transduction in trophoblast 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