Dehydroepiandrosterone Sulfotransferase Gene Induction by Bile Acid Activated Farnesoid X Receptor

Dehydroepiandrosterone sulfotransferase (STD) is a hydroxysteroid sulfo-conjugating enzyme with preferential substrate specificity for C-19 androgenic steroids and C-24 bile acids. STD is primarily expressed in the liver, intestine and adrenal cortex. Earlier studies have shown that androgens inhibit the rat Std promoter function through a negative androgen response region located between −235 and −310 base pair positions (Song, C. S., Jung, M. H., Kim, S. C., Hassan, T., Roy, A. K., and Chatterjee, B. (1998) J. Biol. Chem.273, 21856–21866). Here we report that the primary bile acid chenodeoxycholic acid (CDCA) also acts as an important regulator of the Std gene promoter. CDCA is a potent inducer of the Std gene, and its inducing effect is mediated through the bile acid-activated farnesoid X receptor (FXR), a recently characterized member of the nuclear receptor superfamily. The ligand-activated FXR acts as a heterodimer with the 9-cis-retinoic acid receptor (RXR) and regulates the Std gene by binding to an upstream region at base pair positions −169 to −193. This specific binding region was initially identified by bile acid responsiveness of the progressively deleted forms of the Std promoter in transfected HepG2 hepatoma and enterocyte-like Caco-2 cells. Subsequently, the precise RXR/FXR binding position was established by protein-DNA interaction using in vitro footprinting and electrophoretic mobility shift analyses. Unlike all other previously characterized FXR target genes, which contain an inverted repeat (IR) of the consensus hexanucleotide half-site (A/G)G(G/T)TCA with a single nucleotide spacer (IR-1), the bile acid response element of the Std promoter does not contain any spacer between the two hexanucleotide repeats (IR-0). A promoter-reporter construct carrying three tandem copies of the IR-0 containing −169/−193 element, linked to a minimal thymidine kinase promoter, can be stimulated more than 70-fold in transfected Caco-2 cells upon CDCA treatment. Autoregulation of the STD gene by its bile acid substrate may provide an important contributing role in the enterohepatic bile acid metabolism and cholesterol homeostasis. Dehydroepiandrosterone sulfotransferase (STD) is a hydroxysteroid sulfo-conjugating enzyme with preferential substrate specificity for C-19 androgenic steroids and C-24 bile acids. STD is primarily expressed in the liver, intestine and adrenal cortex. Earlier studies have shown that androgens inhibit the rat Std promoter function through a negative androgen response region located between −235 and −310 base pair positions (Song, C. S., Jung, M. H., Kim, S. C., Hassan, T., Roy, A. K., and Chatterjee, B. (1998) J. Biol. Chem.273, 21856–21866). Here we report that the primary bile acid chenodeoxycholic acid (CDCA) also acts as an important regulator of the Std gene promoter. CDCA is a potent inducer of the Std gene, and its inducing effect is mediated through the bile acid-activated farnesoid X receptor (FXR), a recently characterized member of the nuclear receptor superfamily. The ligand-activated FXR acts as a heterodimer with the 9-cis-retinoic acid receptor (RXR) and regulates the Std gene by binding to an upstream region at base pair positions −169 to −193. This specific binding region was initially identified by bile acid responsiveness of the progressively deleted forms of the Std promoter in transfected HepG2 hepatoma and enterocyte-like Caco-2 cells. Subsequently, the precise RXR/FXR binding position was established by protein-DNA interaction using in vitro footprinting and electrophoretic mobility shift analyses. Unlike all other previously characterized FXR target genes, which contain an inverted repeat (IR) of the consensus hexanucleotide half-site (A/G)G(G/T)TCA with a single nucleotide spacer (IR-1), the bile acid response element of the Std promoter does not contain any spacer between the two hexanucleotide repeats (IR-0). A promoter-reporter construct carrying three tandem copies of the IR-0 containing −169/−193 element, linked to a minimal thymidine kinase promoter, can be stimulated more than 70-fold in transfected Caco-2 cells upon CDCA treatment. Autoregulation of the STD gene by its bile acid substrate may provide an important contributing role in the enterohepatic bile acid metabolism and cholesterol homeostasis. farnesoid X receptor 9-cis-retinoic acid receptor inverted repeat thin layer chromatography oligonucleotide thymidine kinase 5α-dihydrotestosterone 3′-phosphoadenosine 5′-phosphosulfate hepatocyte nuclear factor dehydroepiandrosterone sulfotransferase small heterodimer partner ileal bile acid-binding protein bile salt efflux pump phospholipid transfer protein luciferase fetoprotein transcription factor dehydroepiandrosterone chenodeoxycholic acid lithocholic acid chloramphenicol acetyltransferase electrophoretic mobility shift assay Bile acids modulate gene expression by serving as ligands for the farnesoid X receptor (FXR),1which is a member of the nuclear receptor superfamily. They are produced in the liver as C-24 hydroxysteroid metabolites of cholesterol and serve as intestinal emulsifying agents for hydrophobic nutrients (1Bahar R.J. Stolz A. Gastroenterol. Clin. North Am. 1999; 28: 27-58Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar, 2Russell D.W. Cell. 1999; 97: 539-542Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar, 3Chawla A. Saez E. Evans R.M. Cell. 2000; 103: 1-4Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar). These cholesterol derivatives also function as the autoregulated sensor to modulate the expression of the enzymes and proteins that are involved in bile acid and cholesterol metabolism through enterohepatic re-absorption and fecal excretion. For example, bile acids repress expression of the gene for CYP7A1, the rate-limiting enzyme for the neutral pathway to bile acid biosynthesis, and for CYP8B, a 12α-hydroxylase enzyme that routes the neutral pathway to cholic acid synthesis (2Russell D.W. Cell. 1999; 97: 539-542Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar, 3Chawla A. Saez E. Evans R.M. Cell. 2000; 103: 1-4Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, A. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). Bile acids also by the expression of the a protein that bile acids the E. M. Full Text PDF PubMed Scopus Google Scholar). the other bile acids the for the ileal bile acid-binding protein the bile salt efflux pump the phospholipid transfer protein and the receptor as the small heterodimer partner J. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, M. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, B. C. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, M. A. J. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google ligand-activated FXR forms a heterodimer with the 9-cis-retinoic acid receptor (RXR) and with the bile element of the target gene M. R.M. A. B. 1999; PubMed Scopus Google Scholar, 1999; PubMed Scopus Google Scholar, J. Cell. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). The consensus element for binding of the RXR/FXR heterodimer is an inverted repeat (IR) of the hexanucleotide the two by a single nucleotide J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). This is in the bile acid response of and J. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, M. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, B. C. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, M. A. J. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). to its role in gene the FXR acts to of A. Saez E. Evans R.M. Cell. 2000; 103: 1-4Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, B. C. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, M. A. J. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). the FXR expression that in gene transcription through with the fetoprotein transcription factor which acts as a factor in the and expression of the Unlike the FXR a J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, Biol. 2000; PubMed Scopus Google Scholar). FXR is expressed in the liver, and the that in bile acid metabolism and to to in the bile acid FXR is expressed in the adrenal J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, Biol. 2000; PubMed Scopus Google may also be involved in the of as STD by the is a enzyme that of a of hydroxysteroid as bile and R.M. C. J. PubMed Scopus Google Scholar, J. PubMed Scopus Google Scholar, B. Biol. PubMed Scopus Google Scholar, S. R.J. J. Full Text PDF PubMed Google Scholar, M. A. Biol. PubMed Scopus Google Scholar). of cholesterol to be mediated by two of the hydroxysteroid sulfotransferase acid with STD C. R.M. PubMed Scopus Google Scholar, C. PubMed Scopus Google Scholar). STD the substrate for dehydroepiandrosterone which is a C-19 and for The STD in the rat and have characterized B. PubMed Scopus Google Scholar, C. S. S. R.M. Biol. PubMed Scopus Google Scholar, Biol. PubMed Scopus Google Scholar, B. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). STD is expressed in the liver, small and adrenal R.M. C. J. PubMed Scopus Google J. PubMed Scopus Google Scholar, B. J. Biol. Full Text PDF PubMed Google Scholar, J. S. PubMed Scopus Google Scholar, C. C. R.M. Google Scholar, M. 2000; PubMed Scopus Google Scholar). the also of its bile acid sulfo-conjugating STD is to be an important of the cholesterol through fecal we that the primary bile acid chenodeoxycholic acid a for is a potent inducer of the rat Std promoter and is mediated through a response element located between −169 and Unlike the of the RXR/FXR binding identified in the and the −169/−193 in the Std promoter an IR-0 as the FXR the rat Std promoter the of an FXR target that of bile acids and contributing to cholesterol of and by is a pathway for of and R.M. C. J. PubMed Scopus Google Scholar, in and Scholar, 1999; PubMed Scopus Google Scholar). in cells a of at containing two for the and the other for the R.M. C. J. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, E. J. R.M. 2000; PubMed Scopus Google Scholar). of enzyme substrate which was to be involved in the metabolism of C-19 and in the of androgenic J. R.J. B. Biol. PubMed Scopus Google is to be a enzyme with substrate for bile acids and the liver, the expression of Std the of the in is to be a of the of androgens to androgen which are B. Biol. PubMed Scopus Google J. R.J. B. Biol. PubMed Scopus Google Scholar). the role of bile acid is is to that of bile acids and at the of cholesterol may also in the fecal of bile cholesterol the the we have shown that the produced STD of the primary bile acid CDCA and the bile acid we that the promoter for the rat is by the primary bile acid CDCA in transfected liver and intestinal we that STD gene expression was stimulated in HepG2 and Caco-2 cells CDCA not These the that may be a to the of of bile acids and and and fecal The of the Std gene promoter is of the that are for a of with the and of bile that the bile acid an of the for and the two proteins in the of intestinal bile acids and bile efflux of the A. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, S. J. Biol. Full Text PDF PubMed Google are to enterohepatic of cholesterol of the gene by bile acids is to be important in the of cholesterol J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, M. B. C. B. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). of the for the bile acid protein and the bile acid enzymes to bile acid in the enterohepatic (2Russell D.W. Cell. 1999; 97: 539-542Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar, 3Chawla A. Saez E. Evans R.M. Cell. 2000; 103: 1-4Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, E. M. Full Text PDF PubMed Scopus Google Scholar). The rat Std promoter, its by the bile acid-activated is also by the androgen receptor B. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, B. S. M. S. A. PubMed Scopus Google Scholar). in a two of androgens and bile are also the ligands for two of the nuclear receptor androgen receptor and that the expression of have characterized for in the to in the have not as an heterodimer with the 9-cis-retinoic acid receptor (RXR) and regulates target gene expression by binding to an inverted repeat of a hexanucleotide The binding element for the RXR/FXR heterodimer is an of the (A/G)G(G/T)TCA as the of the that can be a of of binding to a of and FXR J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). target for FXR and that all of contain the FXR with a single nucleotide spacer between the inverted hexanucleotide repeat with the Std gene promoter to an IR-0 as an binding for the RXR/FXR of established the role of IR-0 in the bile acid the −169/−193 element can of a promoter in HepG2 and Caco-2 of the IR-0 by the of the of the at the −169/−193 element is by the is that other transcription are also in we have for the of the nuclear receptor in S. and B. Chatterjee, the the −169/−193 is to the consensus element for A. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). as a factor in the gene expression mediated by the liver X receptor and its partner is also for the expression of the enzyme that of cholic acid in the bile acid is to that and are expressed in the liver and intestine Biol. 2000; PubMed Scopus Google the two that also STD and that a bile acid is by the primary bile acid CDCA in liver and intestinal an IR-0 element to the The role of pathway to be The that are in the rate-limiting enzyme in the pathway to CDCA are to be in bile acid E. D.W. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). These and to the be of to the of Std gene the enterohepatic a role in bile of the role of FXR in Std gene expression may be of Bile acids modulate gene expression by serving as ligands for the farnesoid X receptor (FXR),1which is a member of the nuclear receptor superfamily. They are produced in the liver as C-24 hydroxysteroid metabolites of cholesterol and serve as intestinal emulsifying agents for hydrophobic nutrients (1Bahar R.J. Stolz A. Gastroenterol. Clin. North Am. 1999; 28: 27-58Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar, 2Russell D.W. Cell. 1999; 97: 539-542Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar, 3Chawla A. Saez E. Evans R.M. Cell. 2000; 103: 1-4Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar). These cholesterol derivatives also function as the autoregulated sensor to modulate the expression of the enzymes and proteins that are involved in bile acid and cholesterol metabolism through enterohepatic re-absorption and fecal excretion. For example, bile acids repress expression of the gene for CYP7A1, the rate-limiting enzyme for the neutral pathway to bile acid biosynthesis, and for CYP8B, a 12α-hydroxylase enzyme that routes the neutral pathway to cholic acid synthesis (2Russell D.W. Cell. 1999; 97: 539-542Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar, 3Chawla A. Saez E. Evans R.M. Cell. 2000; 103: 1-4Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, A. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). Bile acids also by the expression of the a protein that bile acids the E. M. Full Text PDF PubMed Scopus Google Scholar). the other bile acids the for the ileal bile acid-binding protein the bile salt efflux pump the phospholipid transfer protein and the receptor as the small heterodimer partner J. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, M. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, B. C. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, M. A. J. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). The ligand-activated FXR forms a heterodimer with the 9-cis-retinoic acid receptor (RXR) and with the bile element of the target gene M. R.M. A. B. 1999; PubMed Scopus Google Scholar, 1999; PubMed Scopus Google Scholar, J. Cell. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). The consensus element for binding of the RXR/FXR heterodimer is an inverted repeat (IR) of the hexanucleotide the two by a single nucleotide J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). This is in the bile acid response of and J. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, M. M. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, B. C. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, M. A. J. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). to its role in gene the FXR acts to of A. Saez E. Evans R.M. Cell. 2000; 103: 1-4Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, B. C. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, M. A. J. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). the FXR expression that in gene transcription through with the fetoprotein transcription factor which acts as a factor in the and expression of the Unlike the FXR a J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, Biol. 2000; PubMed Scopus Google Scholar). FXR is expressed in the liver, and the that in bile acid metabolism and to to in the bile acid FXR is expressed in the adrenal J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, Biol. 2000; PubMed Scopus Google may also be involved in the of as STD by the is a enzyme that of a of hydroxysteroid as bile and R.M. C. J. PubMed Scopus Google Scholar, J. PubMed Scopus Google Scholar, B. Biol. PubMed Scopus Google Scholar, S. R.J. J. Full Text PDF PubMed Google Scholar, M. A. Biol. PubMed Scopus Google Scholar). of cholesterol to be mediated by two of the hydroxysteroid sulfotransferase acid with STD C. R.M. PubMed Scopus Google Scholar, C. PubMed Scopus Google Scholar). STD the substrate for dehydroepiandrosterone which is a C-19 and for The STD in the rat and have characterized B. PubMed Scopus Google Scholar, C. S. S. R.M. Biol. PubMed Scopus Google Scholar, Biol. PubMed Scopus Google Scholar, B. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). STD is expressed in the liver, small and adrenal R.M. C. J. PubMed Scopus Google J. PubMed Scopus Google Scholar, B. J. Biol. Full Text PDF PubMed Google Scholar, J. S. PubMed Scopus Google Scholar, C. C. R.M. Google Scholar, M. 2000; PubMed Scopus Google Scholar). the also of its bile acid sulfo-conjugating STD is to be an important of the cholesterol through fecal we that the primary bile acid chenodeoxycholic acid a for is a potent inducer of the rat Std promoter and is mediated through a response element located between −169 and Unlike the of the RXR/FXR binding identified in the and the −169/−193 in the Std promoter an IR-0 as the FXR the rat Std promoter the of an FXR target that of bile acids and contributing to cholesterol homeostasis. of and by is a pathway for of and R.M. C. J. PubMed Scopus Google Scholar, in and Scholar, 1999; PubMed Scopus Google Scholar). in cells a of at containing two for the and the other for the R.M. C. J. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, E. J. R.M. 2000; PubMed Scopus Google Scholar). of enzyme substrate which was to be involved in the metabolism of C-19 and in the of androgenic J. R.J. B. Biol. PubMed Scopus Google is to be a enzyme with substrate for bile acids and the liver, the expression of Std the of the in is to be a of the of androgens to androgen which are B. Biol. PubMed Scopus Google J. R.J. B. Biol. PubMed Scopus Google Scholar). the role of bile acid is is to that of bile acids and at the of cholesterol may also in the fecal of bile cholesterol the the we have shown that the produced STD of the primary bile acid CDCA and the bile acid we that the promoter for the rat is by the primary bile acid CDCA in transfected liver and intestinal we that STD gene expression was stimulated in HepG2 and Caco-2 cells CDCA not These the that may be a to the of of bile acids and and and fecal The of the Std gene promoter is of the that are for a of with the and of bile that the bile acid an of the for and the two proteins in the of intestinal bile acids and bile efflux of the A. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, S. J. Biol. Full Text PDF PubMed Google are to enterohepatic of cholesterol of the gene by bile acids is to be important in the of cholesterol J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, M. B. C. B. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). of the for the bile acid protein and the bile acid enzymes to bile acid in the enterohepatic (2Russell D.W. Cell. 1999; 97: 539-542Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar, 3Chawla A. Saez E. Evans R.M. Cell. 2000; 103: 1-4Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, E. M. Full Text PDF PubMed Scopus Google Scholar). The rat Std promoter, its by the bile acid-activated is also by the androgen receptor B. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, B. S. M. S. A. PubMed Scopus Google Scholar). in a two of androgens and bile are also the ligands for two of the nuclear receptor androgen receptor and that the expression of have characterized for in the to in the have not as an heterodimer with the 9-cis-retinoic acid receptor (RXR) and regulates target gene expression by binding to an inverted repeat of a hexanucleotide The binding element for the RXR/FXR heterodimer is an of the (A/G)G(G/T)TCA as the of the that can be a of of binding to a of and FXR J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). target for FXR and that all of contain the FXR with a single nucleotide spacer between the inverted hexanucleotide repeat with the Std gene promoter to an IR-0 as an binding for the RXR/FXR of established the role of IR-0 in the bile acid the −169/−193 element can of a promoter in HepG2 and Caco-2 of the IR-0 by the of the of the at the −169/−193 element is by the is that other transcription are also in we have for the of the nuclear receptor in S. and B. Chatterjee, the the −169/−193 is to the consensus element for A. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). as a factor in the gene expression mediated by the liver X receptor and its partner is also for the expression of the enzyme that of cholic acid in the bile acid is to that and are expressed in the liver and intestine Biol. 2000; PubMed Scopus Google the two that also STD and that a bile acid is by the primary bile acid CDCA in liver and intestinal an IR-0 element to the The role of pathway to be The that are in the rate-limiting enzyme in the pathway to CDCA are to be in bile acid E. D.W. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). These and to the be of to the of Std gene the enterohepatic a role in bile of the role of FXR in Std gene expression may be of of and by is a pathway for of and R.M. C. J. PubMed Scopus Google Scholar, in and Scholar, 1999; PubMed Scopus Google Scholar). in cells a of at containing two for the and the other for the R.M. C. J. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, E. J. R.M. 2000; PubMed Scopus Google Scholar). of enzyme substrate which was to be involved in the metabolism of C-19 and in the of androgenic J. R.J. B. Biol. PubMed Scopus Google is to be a enzyme with substrate for bile acids and the liver, the expression of Std the of the in is to be a of the of androgens to androgen which are B. Biol. PubMed Scopus Google J. R.J. B. Biol. PubMed Scopus Google Scholar). the role of bile acid is is to that of bile acids and at the of cholesterol may also in the fecal of bile cholesterol the the we have shown that the produced STD of the primary bile acid CDCA and the bile acid we that the promoter for the rat is by the primary bile acid CDCA in transfected liver and intestinal we that STD gene expression was stimulated in HepG2 and Caco-2 cells CDCA not These the that may be a to the of of bile acids and and and fecal The of the Std gene promoter is of the that are for a of with the and of bile that the bile acid an of the for and the two proteins in the of intestinal bile acids and bile efflux of the A. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. Biol. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, S. J. Biol. Full Text PDF PubMed Google are to enterohepatic of cholesterol of the gene by bile acids is to be important in the of cholesterol J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, M. B. C. B. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). of the for the bile acid protein and the bile acid enzymes to bile acid in the enterohepatic (2Russell D.W. Cell. 1999; 97: 539-542Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar, 3Chawla A. Saez E. Evans R.M. Cell. 2000; 103: 1-4Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, E. M. Full Text PDF PubMed Scopus Google Scholar). The rat Std promoter, its by the bile acid-activated is also by the androgen receptor B. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, B. S. M. S. A. PubMed Scopus Google Scholar). in a two of androgens and bile are also the ligands for two of the nuclear receptor androgen receptor and that the expression of have characterized for in the to in the have not FXR as an heterodimer with the 9-cis-retinoic acid receptor (RXR) and regulates target gene expression by binding to an inverted repeat of a hexanucleotide The binding element for the RXR/FXR heterodimer is an of the (A/G)G(G/T)TCA as the of the that can be a of of binding to a of and FXR J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). target for FXR and that all of contain the FXR with a single nucleotide spacer between the inverted hexanucleotide repeat with the Std gene promoter to an IR-0 as an binding for the RXR/FXR of established the role of IR-0 in the bile acid the −169/−193 element can of a promoter in HepG2 and Caco-2 of the IR-0 by the of the promoter. of the at the −169/−193 element is by the is that other transcription are also in we have for the of the nuclear receptor in S. and B. Chatterjee, the the −169/−193 is to the consensus element for A. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). as a factor in the gene expression mediated by the liver X receptor and its partner is also for the expression of the enzyme that of cholic acid in the bile acid is to that and are expressed in the liver and intestine Biol. 2000; PubMed Scopus Google the two that also STD and that a bile acid is by the primary bile acid CDCA in liver and intestinal an IR-0 element to the The role of pathway to be The that are in the rate-limiting enzyme in the pathway to CDCA are to be in bile acid E. D.W. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). These and to the be of to the of Std gene the enterohepatic a role in bile of the role of FXR in Std gene expression may be of are to for the FXR expression and to Evans for the expression for in and in