Cloning and characterization of a hormonally regulated rat long chain acyl-CoA synthetase

A previously unidentified gonadotropin-regulated long chain acyl-CoA synthe tase (GR-LACS) was cloned and characterized as a 79-kDa cytoplasmic protein expressed in Leydig cells of the rat testis, GR-LACS shares sequence ident ity with two conserved regions of the LACS and luciferase families, includi ng the ATP/AMP binding domain and the 25-aa fatty acyl-CoA synthetase signa ture motif, but displays low overall amino acid similarities (23-28%), GR-L ACS mRNA is expressed abundantly in Leydig cells of the adult testis and to a lesser degree in the seminiferous tubules in spermatogonia and Sertoli c ells. It is also observed in ovary and brain. Immunoreactive protein expres sion was observed mainly in Leydig cells and minimally in the tubules but w as not detected in other tissues, In vivo, treatment with a desensitizing d ose of human chorionic gonadotropin caused transcriptional down-regulation of CR-LACS expression in Leydig cells. The expressed protein present in the cytoplasm of transfected cells displayed acyl-CoA synthetase activity for long chain fatty acid substrates. CR-LACS may contribute to the provision o f energy requirements and to the biosynthesis of steroid precursors and cou ld participate through acyl-CoA's multiple functions in the regulation of t he male gonad.