{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:10:40Z","timestamp":1790831440417,"version":"4.1.0"},"reference-count":23,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,8,1]]},"abstract":"<jats:p>In male mice, deficiency of hormone sensitive lipase (HSL, Lipe gene, E.C.3.1.1.3) causes deficient spermatogenesis, azoospermia, and infertility. Postmeiotic germ cells express a specific HSL isoform that includes a 313 amino acid N-terminus encoded by a testis-specific exon (exon T1). The remainder of testicular HSL is identical to adipocyte HSL. The amino acid sequence of the testis-specific exon is poorly conserved, showing only a 46% amino acid identity with orthologous human and rat sequences, compared with 87% over the remainder of the HSL coding sequence, providing no evidence in favor of a vital functional role for the testis-specific N-terminus of HSL. However, exon T1 is important for Lipe transcription; in mouse testicular mRNA, we identified 3 major Lipe transcription start sites, finding numerous testicular transcription factor binding motifs upstream of the transcription start site. We directly explored two possible mechanisms for the infertility of HSL-deficient mice, using mice that expressed mutant HSL transgenes only in postmeiotic germ cells on a HSL-deficient background. One transgene expressed human HSL lacking enzyme activity but containing the testis-specific N-terminus (HSL\u2212\/\u2212muttg mice). The other transgene expressed catalytically inactive HSL with the testis-specific N-terminal peptide (HSL\u2212\/\u2212atg mice). HSL\u2212\/\u2212muttg mice were infertile, with abnormal histology of the seminiferous epithelium and absence of spermatozoa in the epididymal lumen. In contrast, HSL\u2212\/\u2212atg mice had normal fertility and normal testicular morphology. In conclusion, whereas the catalytic function of HSL is necessary for spermatogenesis in mice, the presence of the N-terminal testis-specific fragment is not essential.<\/jats:p>","DOI":"10.1210\/en.2014-1031","type":"journal-article","created":{"date-parts":[[2014,5,5]],"date-time":"2014-05-05T15:58:08Z","timestamp":1399305488000},"page":"3047-3053","source":"Crossref","is-referenced-by-count":18,"title":["The Catalytic Function of Hormone-Sensitive Lipase is Essential for Fertility in Male Mice"],"prefix":"10.1210","volume":"155","author":[{"given":"Shu Pei","family":"Wang","sequence":"first","affiliation":[{"name":"Divisions of Medical Genetics (S.P.W., J.W.W., H.B., S.C., G.A.M.), Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine and Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada, H3T 1C5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang Wei","family":"Wu","sequence":"first","affiliation":[{"name":"Divisions of Medical Genetics (S.P.W., J.W.W., H.B., S.C., G.A.M.), Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine and Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada, H3T 1C5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Bourdages","sequence":"first","affiliation":[{"name":"Divisions of Medical Genetics (S.P.W., J.W.W., H.B., S.C., G.A.M.), Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine and Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada, H3T 1C5"},{"name":"Valeant Cosm\u00e9derme (H.B.), Laval, Qu\u00e9bec, Canada, H7V 0A3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Fran\u00e7ois","family":"Lefebvre","sequence":"first","affiliation":[{"name":"Hematology (J.F.L., D.L.), Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine and Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada, H3T 1C5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Casavant","sequence":"first","affiliation":[{"name":"Divisions of Medical Genetics (S.P.W., J.W.W., H.B., S.C., G.A.M.), Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine and Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada, H3T 1C5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair R.","family":"Leavitt","sequence":"first","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics (B.R.L.), Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada, V5Z 4H4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Labuda","sequence":"first","affiliation":[{"name":"Hematology (J.F.L., D.L.), Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine and Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada, H3T 1C5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquetta","family":"Trasler","sequence":"first","affiliation":[{"name":"Department of Pediatrics (J.T.), Human Genetics and Pharmacology and Therapeutics, McGill University and Research Institute of the McGill University Health Centre at the Montreal Children\u2019s Hospital, Montr\u00e9al, Qu\u00e9bec, Canada, H3H 1P3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology (C.E.S., L.H.), McGill University, Montr\u00e9al, Qu\u00e9bec, Canada, H3A 2B2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Hermo","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology (C.E.S., L.H.), McGill University, Montr\u00e9al, Qu\u00e9bec, Canada, H3A 2B2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant A.","family":"Mitchell","sequence":"first","affiliation":[{"name":"Divisions of Medical Genetics (S.P.W., J.W.W., H.B., S.C., G.A.M.), Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine and Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada, H3T 1C5"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612494489600_B1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1146\/annurev.nutr.20.1.365","article-title":"Molecular mechanisms regulating hormone-sensitive lipase and lipolysis","volume":"20","author":"Holm","year":"2000","journal-title":"Ann Rev Nutr"},{"key":"2020071612494489600_B2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.humpath.2003.08.015","article-title":"Normal and pathological human testes express hormone-sensitive lipase and the lipid receptors CLA-1\/SR-BI and CD36","volume":"35","author":"Arenas","year":"2004","journal-title":"Hum Pathol"},{"key":"2020071612494489600_B3","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1194\/jlr.M028076","article-title":"HSL-knockout mouse testis exhibits class B scavenger receptor upregulation and disrupted lipid raft microdomains","volume":"53","author":"Casado","year":"2012","journal-title":"J Lipid Res"},{"key":"2020071612494489600_B4","doi-asserted-by":"crossref","first-page":"4272","DOI":"10.1210\/endo.142.10.8424","article-title":"Infertility and testicular defects in hormone-sensitive lipase-deficient mice","volume":"142","author":"Chung","year":"2001","journal-title":"Endocrinology"},{"key":"2020071612494489600_B5","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1073\/pnas.97.2.787","article-title":"Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity","volume":"97","author":"Osuga","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612494489600_B6","doi-asserted-by":"crossref","first-page":"5688","DOI":"10.1210\/en.2004-0919","article-title":"Expression of human hormone-sensitive lipase (HSL) in postmeiotic germ cells confers normal fertility to HSL-deficient mice","volume":"145","author":"Wang","year":"2004","journal-title":"Endocrinology"},{"key":"2020071612494489600_B7","doi-asserted-by":"crossref","first-page":"42875","DOI":"10.1074\/jbc.M403495200","article-title":"The testicular form of hormone-sensitive lipase HSLtes confers rescue of male infertility in HSL-deficient mice","volume":"279","author":"Vallet-Erdtmann","year":"2004","journal-title":"J Biol Chem"},{"key":"2020071612494489600_B8","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1006\/geno.1996.0383","article-title":"Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase","volume":"35","author":"Holst","year":"1996","journal-title":"Genomics"},{"key":"2020071612494489600_B9","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1007\/s003350010185","article-title":"The hormone-sensitive lipase gene is transcribed from at least five alternative first exons in mouse adipose tissue","volume":"11","author":"Laurin","year":"2000","journal-title":"Mamm Genome"},{"key":"2020071612494489600_B10","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1006\/bbrc.2002.6427","article-title":"Characterization of a novel testicular form of human hormone-sensitive lipase","volume":"291","author":"Mairal","year":"2002","journal-title":"Biochem Biophys Res Comm"},{"key":"2020071612494489600_B11","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1194\/jlr.R200009-JLR200","article-title":"Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis","volume":"43","author":"Kraemer","year":"2002","journal-title":"J Lipid Res"},{"key":"2020071612494489600_B12","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1086\/430799","article-title":"Single-gene disorders: what role could moonlighting enzymes play?","volume":"76","author":"Sriram","year":"2005","journal-title":"Am J Hum Genet"},{"key":"2020071612494489600_B13","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1101\/gr.3715005","article-title":"Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes","volume":"15","author":"Siepel","year":"2005","journal-title":"Genome Res"},{"key":"2020071612494489600_B14","first-page":"190","article-title":"New methods for detecting lineage-specific selection","author":"Siepel"},{"key":"2020071612494489600_B15","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/337373a0","article-title":"Genetically haploid spermatids are phenotypically diploid","volume":"337","author":"Braun","year":"1989","journal-title":"Nature"},{"key":"2020071612494489600_B16","doi-asserted-by":"crossref","first-page":"5071","DOI":"10.1073\/pnas.90.11.5071","article-title":"Analysis of the mouse protamine 1 promoter in transgenic mice","volume":"90","author":"Zambrowicz","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612494489600_B17","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/0014-5793(94)00403-X","article-title":"Identification of the active site serine of hormone-sensitive lipase by site-directed mutagenesis","volume":"344","author":"Holm","year":"1994","journal-title":"FEBS Lett"},{"key":"2020071612494489600_B18","first-page":"109","article-title":"Hormone-sensitive lipase and neutral cholesteryl ester lipase","volume":"109","author":"Holm","year":"1999","journal-title":"Methods Mol Biol"},{"key":"2020071612494489600_B19","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ymgme.2008.06.012","article-title":"Lipolysis and the integrated physiology of lipid energy metabolism","volume":"95","author":"Wang","year":"2008","journal-title":"Mol Genet Metab"},{"key":"2020071612494489600_B20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.cmet.2011.12.018","article-title":"FAT SIGNALS\u2013lipases and lipolysis in lipid metabolism and signaling","volume":"15","author":"Zechner","year":"2012","journal-title":"Cell Metab"},{"key":"2020071612494489600_B21","doi-asserted-by":"crossref","first-page":"3333","DOI":"10.1210\/en.2002-220341","article-title":"Hormone-sensitive lipase deficiency in mice causes lipid storage in the adrenal cortex and impaired corticosterone response to corticotropin stimulation","volume":"143","author":"Li","year":"2002","journal-title":"Endocrinology"},{"key":"2020071612494489600_B22","doi-asserted-by":"crossref","first-page":"43615","DOI":"10.1074\/jbc.M301809200","article-title":"Mutational analysis of the hormone-sensitive lipase translocation reaction in adipocytes","volume":"278","author":"Su","year":"2003","journal-title":"J Biol Chem"},{"key":"2020071612494489600_B23","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1126\/science.1090776","article-title":"Generation of viable cholesterol-free mice","volume":"302","author":"Wechsler","year":"2003","journal-title":"Science"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/155\/8\/3047\/10828727\/endo3047.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/155\/8\/3047\/10828727\/endo3047.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T22:02:26Z","timestamp":1594936946000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/155\/8\/3047\/2433313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,1]]},"references-count":23,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2014,8,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2014-1031","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,1]]}}}