Studies on the mechanism of regulation of bile acid synthesis in humans with some aspects on genetic factors

摘要: In the present investigation we studied human bile acid synthesis and its regulation both in vivo vitro also evaluated a possible influence of polymorphisms CYP7A1 CYP8B1 genes on vivo. The following observations were made: • Primary hepatocytes cultured matrigel under serum-free conditions produced acids consistent with pattern vivo, i.e. predominately CA (70%) CDCA (25%), conjugated glycine or taurine. Both glycine-conjugated free suppressed mRNA levels cultures primary order CDCA>DCA>CA>UDCA. Also CYP27A1 but to much lesser extent. Addition GCDCA as well GDCA resulted higher for SHP supporting mechanism by which FXR suppresses through induction SHP. Upregulation humans cholestyramine treatment not only CYP7A1, HNF-4α. This is HNF-4α an important stimulating nuclear factor involved synthesis. Earlier described promoter region gene could be associated variation enzyme activity liver biopsies rate serum 7α-hydroxy-4-cholesten-3-one isotope dilution kinetics. genotypes did differ experiments reporter system transcriptional EMSA analysis measuring binding extracts. Differences ratio gallbladder observed number subjects explained gene. results obtained emphasize marked species differences mechanisms Genetic polymorphism key enzymes does appear major importance this regulation.