title: Lessons from the gonadotropin-regulated long chain acyl-CoA synthetase (GR-LACS) null mouse model: a role in steroidogenesis, but not result in X-ALD phenotype.
abstract: Gonadotropin-regulated long chain fatty acid Acyl-CoA synthetase (GR-LACS), is a member of the LACS family that is regulated by gonadotropin in the rat Leydig cell (LC). Its mouse/human homologs, lipidosin/bubblegum, have been suggested to participate in X-linked adrenoleukodystrophy (X-ALD), an adreno/neurodegenerative disorder with accumulation of very long chain fatty acids (VLCFA) in tissues and plasma. To further gain insights into its regulatory function, a GR-LACS/lipidosin null mouse was generated. No apparent phenotypic abnormalities were observed in the X-ALD target tissues (brain, testis, adrenal). Nuclear inclusions seen in mice >15 month-old, were present in LC of 9 month-old GR-LACS(-/-) mice. LC of the null mice showed refractoriness to the gonadotropin-induced desensitization of testosterone production that is observed in adult animals. LCFAs were moderately increased in the testis, ovary and brain, but not in the adrenal gland of GR-LACS(-/-) mice, with no major changes in VLCFA. No change in LACS activity was observed in these tissues, suggesting a compensatory mechanism exhibited by other LACS members. The GR-LACS(-/-) model did not support its association with X-ALD. These studies revealed a role of GR-LACS in reducing the aging process of the LC, and its participation in gonadotropin-induced testicular desensitization of testosterone production.
authors.affiliation: Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4510, United States.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sheng
authors.forename: Chon-Hwa
authors.initials: CH
authors.lastname: Tsai-Morris
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Maria L
authors.initials: ML
authors.lastname: Dufau
mesh_terms: D000326:Adrenoleukodystrophy / Q000503:physiopathology*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism*; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D007985:Leydig Cells / Q000378:metabolism / Q000648:ultrastructure; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D051381:Rats; D011995:Recombination, Genetic; D013256:Steroids / Q000096:biosynthesis*; D014018:Tissue Distribution
chemical_list: D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D008055:Lipids; D013256:Steroids; D003066:Coenzyme A Ligases; C418138:lipidosin