出版社:American Society for Biochemistry and Molecular Biology
摘要:Scavenger receptor class B type I (SR-BI) contributes to HDL-mediatedcellular cholesterol efflux and is a phagocytosis-inducing phospholipidphosphatidylserine receptor in rat Sertoli cells, whereas thespliced variant of the SR-B gene, SR-BII, is implicated in theefflux of free cholesterol in macrophages. This study aimedto assess whether spontaneous autoimmune orchitis (AIO), whichcauses impaired clearance of apoptotic germ cells and spermatogenicarrest, involves SR-BI, SR-BII, and/or cholesterol. The levelsmeasured during development and the annual reproductive cyclein normal mink were compared with those in mink with spontaneousAIO. Time periods with lowest tubular esterified cholesterol(EC) levels showed maximal SR-BI and SR-BII levels, and theperiods when one or the other SR-BI isoform predominated showedincreased EC levels and spermatogenic arrest in normal minkseminiferous tubules. In tubules with AIO, the predominanceof only one or the other SR-BI isoform was the reverse of thatmeasured in normal tubules, and it was associated with an increasein EC levels but not with apoptosis levels. SR-BI and SR-BIIlevels were not correlated with serum testosterone levels. SR-BImainly localized to the Leydig cell, germ cell, and Sertolicell surface, where its distribution was stage-specific. SR-BIIwas principally intracellular. Tubules from testes with AIOshowed a deregulation of cholesterol homeostasis and SR-BI expressionbut relatively unchanged apoptosis levels. These results suggestthat the expression of both SR-BI isoforms is required for themaintenance of low EC levels and that the predominance of onlyone isoform is associated with the accumulation of EC but notwith apoptosis in the tubules.Supplementary key words scavenger receptor class B type I • Sertoli cell • autoimmune orchitis • cell clearance • Leydig cell