title: Influence of simvastatin, pravastatin, and BM 15.766 on neutral sterols in liver and testis of guinea pigs.
abstract: There is mounting evidence that specific sterol precursors of cholesterol are associated with reproductive functions. Testicular meiosis-activating sterol (T-MAS) and follicular fluid meiosis-activating-sterol (FF-MAS) are 2 cholesterol precursors found in reproductive organs of mammals, which are able to overcome meiotic arrest in vitro. This study investigates the influence of simvastatin and pravastatin, 2 inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, and BM 15.766, an inhibitor of 7-dehydrocholesterol reductase, on concentrations of neutral sterols in liver and testis of guinea pigs. Concentrations of T-MAS, lathosterol, and desmosterol were markedly higher in testis compared with liver. Simvastatin (150 mg/d) and pravastatin (150 mg/d and 350 mg/d) markedly reduced cholesterol precursors in liver. In contrast, T-MAS and desmosterol in testis remained unchanged, albeit other cholesterol precursors were reduced. BM 15.766 led to the accumulation of 7- and 8-dehydrocholesterol, both in liver and testis. However, concentrations of T-MAS in testis were not changed by BM 15.766. We conclude that treatment of guinea pigs with simvastatin, pravastatin, or BM 15.766, which simulates the biochemical defect of the Smith-Lemli-Opitz (SLO) syndrome, does not affect T-MAS concentrations in testis.
authors.affiliation: Department of Clinical Pharmacology, University of Bonn, Bonn, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lindenthal
authors.forename: Thomas
authors.initials: T
authors.lastname: Bertsch
authors.forename: Klaus
authors.initials: K
authors.lastname: Fassbender
authors.forename: Mark
authors.initials: M
authors.lastname: Stroick
authors.forename: Sandra
authors.initials: S
authors.lastname: Kühl
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.forename: Klaus
authors.initials: K
authors.lastname: von Bergmann
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000096:biosynthesis; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D017035:Pravastatin / Q000494:pharmacology*; D019821:Simvastatin / Q000494:pharmacology*; D013261:Sterols / Q000378:metabolism*; D013737:Testis / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010879:Piperazines; D013261:Sterols; C047457:BM 15766; D002784:Cholesterol; D019821:Simvastatin; D017035:Pravastatin