Influence of simvastatin, pravastatin, and BM 15.766 on neutral sterols in liver and testis of guinea pigs.
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.
Lindenthal
Bernhard
B
Department of Clinical Pharmacology, University of Bonn, Bonn, Germany.
Bertsch
Thomas
T
Fassbender
Klaus
K
Stroick
Mark
M
Kühl
Sandra
S
Lütjohann
Dieter
D
von Bergmann
Klaus
K
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*
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010879:Piperazines; D013261:Sterols; C047457:BM 15766; D002784:Cholesterol; D019821:Simvastatin; D017035:Pravastatin