{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:43:07Z","timestamp":1791240187112,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T00:00:00Z","timestamp":1594512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>It has recently been suggested that the hypergonadotropic hypogonadism characterizing Klinefelter syndrome (KS) might not be due to a steroidogenic dysfunction per se, but mainly to an altered testosterone (T) secretion into the bloodstream. However, the Leydig cell functionality remains incompletely studied in KS, and new markers should be considered. Previous data indicated that chronic hCG stimulation influences the production of both insulin\u2010like peptide 3 (INSL3) and 25\u2010hydroxy\u2010vitamin D (25\u2010VD) in eugonadal men.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim of the study<\/jats:title><jats:p>To evaluate INSL3 and 25\u2010VD serum levels, as markers of Leydig cell functionality, in association with sex steroids, after an acute hCG test in a group of KS patients and healthy volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective analysis of a prospective case\u2010control clinical trial was carried out. KS patients (n\u00a0=\u00a011) and age\u2010matched healthy controls (n\u00a0=\u00a011) provided a basal blood sample (V0) immediately followed by a single intramuscular injection of hCG 5000\u00a0IU. Blood samples were taken in the following five days (V1\u2010V5).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At baseline, INSL3 was lower in KS patients compared with controls (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.007). When adjusted for INSL3 levels, the production of steroids was similar between KS patients and controls. 25\u2010VD was in the insufficient range both in KS patients and in controls and was not different (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.064). Acute hCG stimulation increased neither INSL3 nor 25\u2010VD in both KS patients and controls. In controls, an inverse correlation was detected between INSL3 levels and body mass index (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.020) and waist circumference (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.020).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>INSL3 secretion is independent from steroidogenesis, and its production is mostly not influenced by acute hCG stimulation both in KS men and in controls. INSL3 serum levels should be considered as a marker of Leydig cell differentiation and numbers rather than steroidogenesis. 25\u2010VD serum levels are also not increased by a single acute hCG administration, which was not able to restore the normal concentrations of 25\u2010VD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12851","type":"journal-article","created":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T21:14:39Z","timestamp":1593292479000},"page":"1720-1727","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effects of acute hCG stimulation on serum INSL3 and 25\u2010OH vitamin D in Klinefelter syndrome"],"prefix":"10.1111","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6607-7105","authenticated-orcid":false,"given":"Daniele","family":"Santi","sequence":"first","affiliation":[{"name":"Unit of Endocrinology Department of Medical Specialties Azienda Ospedaliero\u2010Universitaria of Modena Modena Italy"},{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Ivell","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Nottingham Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravinder","family":"Anand\u2010Ivell","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Nottingham Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"De Toni","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaminia","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology and Prevention and Care of Diabetes and Centre for Applied Biomedical Research Sant'Orsola Hospital Bologna Italy"},{"name":"Department of Medical and Surgical Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Mezzullo","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology and Prevention and Care of Diabetes and Centre for Applied Biomedical Research Sant'Orsola Hospital Bologna Italy"},{"name":"Department of Medical and Surgical Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6390-2146","authenticated-orcid":false,"given":"Carla","family":"Pelusi","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology and Prevention and Care of Diabetes and Centre for Applied Biomedical Research Sant'Orsola Hospital Bologna Italy"},{"name":"Department of Medical and Surgical Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uberto","family":"Pagotto","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology and Prevention and Care of Diabetes and Centre for Applied Biomedical Research Sant'Orsola Hospital Bologna Italy"},{"name":"Department of Medical and Surgical Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Belli","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology Department of Medical Specialties Azienda Ospedaliero\u2010Universitaria of Modena Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio R. 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