{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T03:05:13Z","timestamp":1767927913856,"version":"3.49.0"},"reference-count":82,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"E-Rare Research Programme ERA-NET E-Rare 3 \u201cTreatPolyQ\u201d","award":["01GM1804"],"award-info":[{"award-number":["01GM1804"]}]},{"name":"E-Rare Research Programme ERA-NET E-Rare 3 \u201cTreatPolyQ\u201d","award":["643417"],"award-info":[{"award-number":["643417"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["01GM1804"],"award-info":[{"award-number":["01GM1804"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["643417"],"award-info":[{"award-number":["643417"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Body weight (BW) loss and reduced body mass index (BMI) are the most common peripheral alterations in Huntington disease (HD) and have been found in HD mutation carriers and HD animal models before the manifestation of neurological symptoms. This suggests that, at least in the early disease stage, these changes could be due to abnormal tissue growth rather than tissue atrophy. Moreover, BW and BMI are reported to be more affected in males than females in HD animal models and patients. Here, we confirmed sex-dependent growth alterations in the BACHD rat model for HD and investigated the associated contributing factors. Our results showed growth abnormalities along with decreased plasma testosterone and insulin-like growth factor 1 (IGF-1) levels only in males. Moreover, we demonstrated correlations between growth parameters, IGF-1, and testosterone. Our analyses further revealed an aberrant transcription of testosterone biosynthesis-related genes in the testes of BACHD rats with undisturbed luteinizing hormone (LH)\/cAMP\/PKA signaling, which plays a key role in regulating the transcription process of some of these genes. In line with the findings in BACHD rats, analyses in the R6\/2 mouse model of HD showed similar results. Our findings support the view that mutant huntingtin may induce abnormal growth in males via the dysregulation of gene transcription in the testis, which in turn can affect testosterone biosynthesis.<\/jats:p>","DOI":"10.3390\/cells11233779","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T04:56:25Z","timestamp":1669611385000},"page":"3779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evidences for Mutant Huntingtin Inducing Musculoskeletal and Brain Growth Impairments via Disturbing Testosterone Biosynthesis in Male Huntington Disease Animals"],"prefix":"10.3390","volume":"11","author":[{"given":"Libo","family":"Yu-Taeger","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, Germany"},{"name":"Institute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianna","family":"Novati","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, Germany"},{"name":"Institute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3758-1569","authenticated-orcid":false,"given":"Jonasz Jeremiasz","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, Germany"},{"name":"Institute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6669-9676","authenticated-orcid":false,"given":"Elisabeth","family":"Singer-Mikosch","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, Germany"},{"name":"Institute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann-Sophie","family":"Pabst","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fubo","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Saft","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ruhr University Bochum, 44801 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Koenig","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ruhr University Bochum, 44801 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisa","family":"Ellrichmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ruhr University Bochum, 44801 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taneli","family":"Heikkinen","sequence":"additional","affiliation":[{"name":"Charles River Discovery Services, 70210 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud A.","family":"Pouladi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"},{"name":"British Columbia Children\u2019s Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf","family":"Riess","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, Germany"},{"name":"Center for Rear Disease [ZSE], University of Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6139-788X","authenticated-orcid":false,"given":"Huu Phuc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Faculty of Medicine, Ruhr University Bochum, 44801 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosomes. 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