{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T11:51:04Z","timestamp":1792324264337,"version":"4.4.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Ko\u00e7 University Research Center for Translational Medicine"},{"name":"Republic of Turkey Ministry of Development Research Infrastructure Support Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Human chorionic gonadotropin (hCG) is a luteotropic hormone that promotes the survival and steroidogenic activity of corpus luteum (CL) by acting through luteinizing hormone receptors (LHRs) expressed on luteinized theca and granulosa cells (GCs). Therefore, it is used to support luteal phase in in vitro fertilization (IVF) cycles to improve clinical pregnancy rates and prevent miscarriage. However, the molecular mechanism underlying this action of hCG is not well characterized. To address this question, we designed an in vitro translational research study on the luteal GCs obtained from 58 IVF patients. hCG treatment at different concentrations and time points activated c-Jun N-terminal kinase (JNK) pathway and significantly increased its endogenous kinase activity along with upregulated expression of steroidogenic enzymes (steroidogenic acute regulatory protein (stAR), 3\u03b2-Hydroxysteroid dehydrogenase (3\u03b2-HSD)) in a dose-dependent manner in the luteal GCs. As a result, in vitro P production of the cells was significantly enhanced after hCG. When JNK pathway was inhibited pharmacologically or knocked-down with small interfering RNA luteal function was compromised, P4 production was declined along with the expression of stAR and 3\u03b2-HSD in the cells. Further, hCG treatment after JNK inhibition failed to correct the luteal defect and promote P4 output. Similar to hCG, luteinizing hormone (LH) treatment improved luteal function as well and this action of LH was associated with JNK activation in the luteal GCs. These findings could be important from the perspective of CL biology and luteal phase in human because we for the first time identify a critical role for JNK signaling pathway downstream LHR activation by hCG\/LH in luteal GCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary Sentence<\/jats:title>\n                    <jats:p>JNK signaling pathway plays a central role in the upregulated expression of the steroidogenic enzymes StAR and 3b-HSD and augmented progesterone production by hCG\/LH in human luteal granulosa cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/biolre\/ioaa034","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T07:57:47Z","timestamp":1583999867000},"page":"1270-1280","source":"Crossref","is-referenced-by-count":25,"title":["hCG Improves Luteal Function and Promotes Progesterone Output through the Activation of JNK Pathway in the Luteal Granulosa Cells of the Stimulated IVF Cycles\u2020"],"prefix":"10.1093","volume":"102","author":[{"given":"Gamze","family":"Bildik","sequence":"first","affiliation":[{"name":"Graduate School of Health Sciences, Koc University, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazli","family":"Akin","sequence":"first","affiliation":[{"name":"Graduate School of Health Sciences, Koc University, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashar","family":"Esmaeilian","sequence":"first","affiliation":[{"name":"Graduate School of Health Sciences, Koc University, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesko","family":"Hela","sequence":"first","affiliation":[{"name":"Graduate School of Health Sciences, Koc University, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayhan","family":"Yakin","sequence":"first","affiliation":[{"name":"Graduate School of Health Sciences, Koc University, Istanbul, Turkey"},{"name":"Department of Obstetrics and Gynecology, Koc University School of Medicine, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamer","family":"Onder","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, School of Medicine, Koc University, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bulent","family":"Urman","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Koc University School of Medicine, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozgur","family":"Oktem","sequence":"first","affiliation":[{"name":"Graduate School of Health Sciences, Koc University, Istanbul, Turkey"},{"name":"Department of Obstetrics and Gynecology, Koc University School of Medicine, Istanbul, 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