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Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Recent studies reveal that bile acids, also are signaling molecules that activate several nuclear receptors and regulate many physiological pathways and processes to maintain bile acid and cholesterol homeostasis. Mutations of the principal regulatory genes in bile acid biosynthetic pathways have recently been identified in human patients with hepatobiliary and cardiovascular diseases. Genetic manipulation of key regulatory genes and bile acid receptor genes in mice have been obtained. These advances have greatly improved our understanding of the molecular mechanisms underlying complex liver physiology but also raise many questions and controversies to be resolved. These developments will lead to early diagnosis and discovery of drugs for treatment of liver and cardiovascular diseases. liver orphan receptor; farnesoid X receptor; cholesterol 7[alpha]-hydroxylase cytochrome P-450; cholesterol homeostasis; gene regulation

Bile acids are cytoprotective in hepatocytes by activating phosphatidylinositol-3-kinase (PI3-K) and its downstream signal AKT. Our aim was to determine whether feeding taurocholate to C[Cl.sub.4]-treated rats reduces cholangiocyte apoptosis and whether this cytoprotective effect is dependent on PI3-K. Cholangiocyte proliferation, secretion, and apoptosis were determined in cholangiocytes from bile duct ligation (BDL), C[Cl.sub.4]-treated BDL rats, and C[Cl.sub.4]-treated taurocholate-fed rats. In vitro, we tested whether C[Cl.sub.4] induces apoptosis and whether loss of cholangiocyte proliferation and secretion is dependent on PI3-K. The C[Cl.sub.4]-induced cholangiocyte apoptosis and loss of cholangiocyte proliferation and secretion were reduced in C[Cl.sub.4]-treated rats fed taurocholate. C[Cl.sub.4]-induced cholangiocyte apoptosis, loss of cholangiocytes secretion, and proliferation were prevented by preincubation with taurocholate. Taurocholate cytoprotective effects were ablated by wortmannin. Taurocholate prevented, in vitro, C[Cl.sub.4]-induced decrease of phosphorylated AKT protein expression in cholangiocytes. The cytoprotective effects of taurocholate on C[Cl.sub.4] effects on cholangiocyte proliferation and secretion were abolished by wortmannin. Taurocholate protects cholangiocytes from C[Cl.sub.4]-induced apoptosis by a PI3-K-dependent mechanism. Bile acids are important in the prevention of drug-induced ductopenia in cholangiopathies. cytoprotection; biliary epithelium; bile acids

Gallstones develop when the secretion of cholesterol is elevated compared with the secretion of bile acids into bile. One of the risk factors for the formation of gallstones is pregnancy. Because the pregnancy-induced increase in hepatic cholesterol synthesis rates could play a critical role in the development of cholesterol stones, the aim of the present study was to determine whether stone formation, as assessed by the ratio of cholesterol to bile acids in bile, could be ablated by blocking the pregnancy-induced increase in hepatic sterol synthesis rates. Golden Syrian hamsters were fed either ground chow or chow supplemented with 0.5% cholesterol for 3 wk and studied in the nonpregnant state or in late gestation. In chow-fed animals, a 1.6-fold increase in the ratio of cholesterol to bile acids occurred simultaneously with a sevenfold increase in hepatic sterol synthesis rate and a ninefold increase in the amount of newly synthesized cholesterol secreted into the bile in late gestation. In the cholesterol-fed dams, an increase in the ratio of cholesterol to bile acids occurred even with the lack of induction of hepatic sterol synthesis rates during pregnancy. Thus it appears that the marked induction of hepatic sterol synthesis rates during gestation is not essential for the pregnancy-induced cholesterol saturation of bile when cholesterol is fed to animals. gallstones; gestation

Background and aims: C-myc over expression is implicated in malignancy although to date this has not been studied in Barrett's metaplasia. We sought to determine c-myc expression in the malignant [...]

Research has been conducted on circulating bile acids. The reabsorption of these acids by ileal sodium/bile acid cotransporter has been investigated and the decription of the bile acid reabsorption inhibitors is presented.

Research has been conducted on substrate specificities between Escherichia coli AcrB and AcrD. The functional chimeras of these proteins demonstrate that large periplasmis loops of these proteins are responsible for drug specificity.

This study was performed with growing chickens (4 to 22 d of age) to evaluate the effects of feeding a rye-based diet supplemented with commercial enzyme preparation containing xylanase and [beta]-glucanase (Quatrazyme HP, Nutri-Tomen, France) on small intestine wall morphology, bile acid composition, nutrient digestibility, and bird performance compared with unsupplemented rye- or corn-based diets. The rye-based diet decreased (P [less than or equal to] 0.05) weight gain, feed intake, and feed efficiency and increased water intake compared with the corn-based diet. Moreover, rye consumption reduced crude fat and protein digestibility as well as apparent metabolizable energy (P [less than or equal to] 0.05). The small intestine wall showed that villus length, width, and surface were decreased in broiler chickens fed the rye-based diet compared with those fed the corn-based diet. However, crypt morphometry parameters were not affected by diet type. The concentration of conjugated bile acids in the small intestine contents of broiler chickens fed the rye-based diet was decreased (P [less than or equal to] 0.05) compared with those fed the corn-based diet. These findings suggest that feeding a rye-based diet reduces villus capacity for nutrient absorption and bile acid capacity for fat solubilization and emulsification, resulting in decreased bird performance. The addition of xylanase and [beta]-glucanase to the rye-based diet improved (P [less than or equal to] 0.05) weight gain, feed intake, and feed efficiency, and decreased water intake. The digestibility of nutrients and apparent metabolizable energy were also increased (P [less than or equal to] 0.05). Addition of xylanase and [beta] glucanase increased (P [less than or equal to] 0.05) villus size and the villus height-to-crypt depth ratio, as well as the concentration of conjugated bile acids (P [less than or equal to] 0.05) in the small intestine contents. Exogenous enzymes improved nutrient digestibility and broiler chicken performance, probably by improving the absorption capacity of the small intestine through increased villus surface and intestinal concentration of conjugated bile acids. Key Words: Bile Acids, Broilers, [beta]-glucanase, Rye, Villi, Xylan 1,4-[beta]-xylosidase

We have previously shown that cAMP protects against bile acid-induced apoptosis in cultured rat hepatocytes in a phosphoinositide 3-kinase (PI3K)-dependent manner. In the present studies, we investigated the mechanisms involved in this anti-apoptotic effect. Hepatocyte apoptosis induced by glycodeoxycholate (GCDC) was associated with mitochondrial depolarization, activation of caspases, the release of cytochrome c from the mitochondria, and translocation of BAX from the cytosol to the mitochondria, cAMP inhibited GCDC-induced apoptosis, caspase 3 and caspase 9 activation, and cytochrome c release in a PI3K-dependent manner. cAMP activated PI3K in p85 immunoprecipitates and resulted in PI3K-dependent activation of the survival kinase Akt. Chemical inhibition of Akt phosphorylation with SB-203580 partially blocked the protective effect of cAMP. cAMP resulted in wortmannin-independent phosphorylation of BAD and was associated with translocation of BAD from the mitochondria to the cytosol. These results suggest that GCDC-induced apoptosis in cultured rat hepatocytes proceeds through a caspase-dependent intracellular stress pathway and that the survival effect of cAMP is mediated in part by PI3K-dependent Akt activation at the level of the mitochondria. phosphoinositide 3-kinase; Akt; cholestasis; BAX; adenosine 3',5'-cyclic monophosphate

We investigated prostanoid biogenesis by human colonic fibroblasts (CCD-18Co cells and nine primary fibroblast cultures) exposed to a primary (cholic, CA) or a secondary (deoxycholic, DCA) bile acid. Basal PG[E.sub.2] levels in CCD-18Co cultures and fibroblast strains initiated from normal and adenocarcinomatous colon, respectively, were 1.7 [+ or -] 0.3, 4.0 [+ or -] 2.0, and 15.0 [+ or -] 4.8 ng/mg protein. Peak levels 24 h after exposure to DCA (300 [micro]M) rose, respectively, seven-, six- and sevenfold, but CA elicited no such responses. Increases in PG[E.sub.2] synthesis were preceded by sequential increases in PGH synthase-2 mRNA and protein expression and were fully prevented by a nonselective (indomethacin) or a selective (celecoxib) nonsteroidal anti-inflammatory drug. DCA, but not CA, caused abrupt, transient increases in fibroblast intracellular [Ca.sup.2+] concentration ([[[Ca.sup.2+]].sub.i]) ~1 min after exposure. Increased [[[Ca.sup.2+]].sub.i] was required for DCA-mediated induction of PG[E.sub.2] synthesis, and protein kinase C was a further essential component of this signaling pathway. Colonic fibroblasts may be a major target for prostanoid biogenesis induced by fecal bile acids and, potentially, other noxious actions of these agents. colorectal neoplasms; feces; mesenchymal cells; prostaglandin H synthases

Sham-operated and cecectomized rats were fed for 21 d a cholesterol-free purified diet containing (200 g/kg) either normal cornstarch (CS) or high amylose cornstarch (HACS). In both types of rats, those fed the HACS diet had a significantly lower plasma total cholesterol concentration and a significantly larger intestinal bile acid pool than those fed the CS diet. In cecectomized rats, those fed the HACS diet had significantly lower plasma HDL and LDL cholesterol concentrations, a significantly greater fecal bile acid excretion and a significantly lower hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase mRNA concentration than those fed the CS diet. The plasma triglyceride concentration and LDL-receptor mRNA concentration were not affected by the diet or cecectomy. In sham-operated rats, the propionate concentration in the cecal contents was significantly greater in those fed the HACS diet than in those fed the CS diet. Compared with sham-operated rats, cecectomized rats had significantly enhanced cholesterol 7[alpha]-hydroxylase activity. In intact rats, biliary bile acid flux into the small intestine was significantly greater in those fed the HACS diet than in those fed the CS diet. Thus, the hypocholesterolemic effect of HACS appears to be mediated by accelerated fecal excretion of bile acids and increases in the intestinal pool and biliary flux of bile acids, and not by cecal fermentation products. KEY WORDS: * high amylose cornstarch * cecectomy * plasma cholesterol * rats

Research has been conducted on the substituted cinnamic acids. The asymmetric epoxidation of these acids which has been obtained in the presence of keto bile acid derivatives as optically active carbonyl inducers has been investigated and is described.

Huntington's disease (HD) is an untreatable neurological disorder caused by selective and progressive degeneration of the caudate nucleus and putamen of the basal ganglia. Although the etiology of HD pathology is not fully understood, the observed loss of neuronal cells is thought to occur primarily through apoptosis. Furthermore, there is evidence in HD that cell death is mediated through mitochondrial pathways, and mitochondrial deficits are commonly associated with HD. We have previously reported that treatment with tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, prevented neuropathology and associated behavioral deficits in the 3-nitropropionic acid rat model of HD. We therefore examined whether TUDCA would also be neuroprotective in a genetic mouse model of HD. Our results showed that systemically administered TUDCA led to a significant reduction in striatal neuropathology of the R6/2 transgenic HD mouse. Specifically, R6/2 mice began receiving TUDCA at 6 weeks of age and exhibited reduced striatal atrophy, decreased striatal apoptosis, as well as fewer and smaller size ubiquitinated neuronal intranuclear huntingtin inclusions. Moreover, locomotor and sensorimotor deficits were significantly improved in the TUDCA-treated mice. In conclusion, TUDCA is a nontoxic, endogenously produced hydrophilic bile acid that is neuroprotective in a transgenic mouse model of HD and, therefore, may provide a novel and effective treatment in patients with HD.

Research has been conducted on the bile acids. The synthesis of different polymers carried out from these acids and the applications proposed for such polymers are discussed.

Research has been conducted on the mammalian sodium/bile acid cotransporters, the glycoproteins with the exoplasmic N-terminus, various transmembrane regions and cytoplasmic C-terminus. The hypothesis that the membrane-embedded regions are the transmembrane or membrane-associated segments in the liver bile acid transporter has been examined and the details are presented.

Most Gram-positive bacteria are susceptible to the bactericidal action of fatty acids and bile acids. Because dietary calcium phosphate (CaP[sub.i]) lowers the intestinal concentration of these antimicrobial agents, high CaP[sub.i] intake may enhance intestinal colonization of Gram-positive pathogens and the subsequent pathogenesis. In this study, we tested this hypothesis in a rat model using Listeria monocytogenes. Rats were fed diets containing low (20 [micro]mol/g diet) or high (160 [micro]mol/g diet) amounts of CaP[sub.i]. Dietary fat was provided as corn oil or milk fat. Rats were orally inoculated with L. monocytogenes. When rats consumed diets containing corn oil, high CaP[sub.i] intake indeed stimulated colonization of L. monocytogenes and increased L. monocytogenes translocation and diarrhea. In addition, supplemental CaP[sub.i] enhanced ex vivo growth of L. monocytogenes in fecal extracts of rats fed corn oil diets, suggesting that high CaP[sub.i] intake decreased a luminal inhibitory factor. The concentrations of bile salts and fatty acids, which were highly listericidal in vitro, were indeed considerably decreased in fecal water of rats in the high calcium corn oil group. Surprisingly, dietary CaP[sub.i] did not affect colonization and translocation of L. monocytogenes in rats fed the milk fat diet, nor did CaP[sub.i] enhance ex vivo growth in fecal extracts. This absence of Listeria stimulation was associated with a lack of effect of dietary CaP[sub.i] on fecal soluble fatty acids. In addition, residual soluble bile salts were higher in rats fed the high CaP[sub.i] milk fat diet compared with the high CaP[sub.i] corn oil diet. These results suggest that the stimulating effect of CaP[sub.i] on L. monocytogenes infection depends on the type of dietary fat consumed. Key Words: * calcium * dietary fat * fatty acids * bile acids * infection * rats

Multidrug resistance-associated protein 3 (MRP3; symbol ABCC3), has been shown to mediate ATP-dependent transport of organic anions including 17[beta]-glucuronosyl estradiol, glucuronosyl bilirubin, monovalent, and sulfated bile salts. MRP3 mRNA expression was reported in rat intestine suggesting a role of MRP3 in the intestinal transport. We examined the expression and localization of MRP3 in rat small and large intestine by RT-PCR, immunofluorescence, and immunoblot analysis. MRP3 was identified in all intestinal segments by RT-PCR. MRP3 expression was low in duodenum and jejunum but markedly increased in ileum and colon. With the use of a rat MRP3 specific antibody, MRP3 was localized to the basolateral domains of enterocytes. Immunofluorescence analysis and immunoblot analysis confirmed a strong expression of rat MRP3 in ileum and colon. In contrast, MRP2 was predominantly expressed in the proximal segments of rat small intestine. Our findings demonstrate a high expression of rat MRP3 in ileum and colon and provide evidence for an involvement of MRP3 in the ATP-dependent transport of organic anions, including bile salts from the enterocyte into blood. enterohepatic circulation; intestinal transport; organic anions; bile acids

Research has been conducted on the human type III 3(alpha)-hydroxysteroid dehydrogenase/bile acid binding protein complexed with NADP (super)+ and ursodeoxycholate. The crystal structure of this compound has been investigated and the results are presented.

Research has been conducted on the bile acids. The use of these acids as the building block for the dendritic unit construction has been explored and the results indicate that these molecules have globular shapes with the nanometric dimensions.

Results reveal that the 3-hydroxyl group plays a critical role in anchoring monohydroxy bile acids and their salts to the aqueous interface and condense into phospholipid membranes. Data indicate the bile acids in association with phosphatidylcholine monolayer at low pH than at high pH.

Research demonstrates that intestinal Lactobacillus accumulates bile acids as shown by the accumulation of cholic acid. Data indicate that the acid uptake is mediated by the transmembrane proton gradient.

Recently published work that establishes a specific role for the nuclear receptor FXR in cholesterol catabolism pathways and in repression of the CYP7A1 gene and regulation by nuclear receptors, is discussed in this review article. The rate-limiting step of the neutral bile biosynthesis pathway is catalyzed by the cytochrome P450 cholesterol 7alpha-hydroxylase or CYP7A1. Lipid homeostasis in vertebrates, that is, the acquisition, synthesis and metabolism of cholesterol, is important. As mediators of organ physiology, nuclear hormone receptors, and other proteins are thought to play a vital role in the processes by controlling the transcription of genes encoding the transporters, the apoplipoproteins, as well as catabolic and synthetic enzymes. Implications for future drug development in treatment of hypercholesterolemia and cholestasis are important.

The authors dicuss the role of the nuclear bile acid receptor FXR/BAR as an intracellular bile acide sensor in lipid and bile accid homeostasis.

Hepatic cholesterol 7(alpha)-hydroxylase (CYP7A) and sterol 27 hydroxylase activities were measured in fetal, newborn, suckling, and weaned piglets from 76 d into gestation to 49 d of age. Hepatic CYP7A activity was not detected in fetal microsomes, but it increased to 6.8 +/- 2.6 pmol/min*mg(super -1) protein in suckling piglets at 21 d of age and to 18.2 +/- 2.5 in weaned piglets at 49 d of age. Hepatic CYP7A activity was not different between 49-d-old piglets weaned at 21 d and piglets suckled for 49 d (18.9 +/- 2.6 and 18.2 +/- 2.5 pmol/min*mg protein, respectively). Fasting for 14 h decreased CYP7A activity by 86% in both suckled and weaned piglets. Cholesterol 7(alpha)-hydroxylase activity remained decreased for at least 5 h after refeeding. Sterol 27-hydroxylase activity was also undetectable near birth, but was detectable by 21 d of age. Postnatally, sterol 27-hydroxylase activity was not influenced by age or suckling and weaning, as was CYP7A. Sterol 27-hydroxylase was decreased by 80% in piglets deprived of feed compared with piglets given free access. In contrast to CYP7A activity, 27-hydroxylase activity returned within 5 h after refeeding to levels observed in piglets given ad libitum access to feed. Similar to CYP7A enzyme activity, hepatic CYP7A mRNA was not detected in newborn piglets, but increased from 2.7 +/- 1.7. pg mRNA/(mu)g RNA in suckling piglets at 21 d to 13.7 +/- 1.2 in 49-d-old piglets weaned at 21 d. As with enzyme activity, feed deprivation decreased CYP7A mRNA to barely detectable levels (< .5 pg/(mu)g RNA), and which remained decreased for at least 5 h following refeeding (.6 +/- .3 and 2.67 +/- .4 pg mRNA/(mu)g RNA for suckled and weaned piglets, respectively). In piglets allowed free access to feed, CYP7A mRNA concentrations were associated positively (P = .001) with enzyme activity. These results suggest that developmental regulation of CYP7A activity is the result of a pretranslational mechanism. Key Words: Bile Acids, Cholesterol Hydroxylase, Messenger RNA, Piglets, Suckling, Weaning

Research describes a mathematical model incorporating parameters of cell adsorption that influence the survival of bifidobacteria after exposure to gastic and intestinal fluids. Data show that cell death rate in the beads decreases in relation to alginate concentration and the bead size.

Two strains of mice with genetic differences in cholesterol absorption were examined with regard to cholesterolemic response. Results showed that 129/Sv mice absorbed twice as efficiently as C57BL/6 mice when fed a diet that was low in cholesterol. When fed lipid-enriched diets, the 129/Sv mice became more hypercholesterolemic than the C57BL/6 mice. The 129/Sv mice also had higher hepatic cholesterol levels. Analysis indicates that cholesterol absorption was not influenced by physicochemical factors but were linked to genetic differences in the translocation of sterol across epithelial cells.

Research was conducted to elucidate the mechanism of absorption of conjugated bile acid at the apical membrane of jejunal epithelial cells. Brush-border membrane vesicles were prepared and the absorption of two taurine-conjugated bile acids that are representative of endogenous bile acids in many variate vertebrate species were examined. Results showed that the absorption of conjugated bile acids in the jejunum from the rat is caused by anion exchange and is most probably an antiport transport.

The role of the biliary epithelial cells in lipid and sterol metabolism was investigated using immortalized bile duct cells. The bile duct cells were derived from transgenic mice with the SV40 thermosensitive immortalizing mutant gene ts458. Experimental results showed that biliary epithelium actively synthesizes lipids and appears to directly contribute bile acids to the biliary fluid in vivo. The presence of cholesterol 7alpha- and 26R-hydroxylases were also identified, suggesting their role in bile acid formation.

A study was conducted to analyze the function of potassium channels in bile acid-independent bile flow in the isolated and bile duct-cannulated perfused rat liver. The driving force on K+ was changed and different K+ channel blockers were utilized to carry out the study. Results indicated that partial cholestasis induced by the K+ channel blockers Ba2+ and tetraethylammonium occurs by significantly different mechanisms.

Na+-glucose cotransport has been previously demonstrated to be inhibited by a decline in the cotransporter numbers in rabbits, while Na+-amino acid cotransport was inhibited by a reduction in the affinity for the amino acid. It is further established that Na+-bile acid cotransport decreases in villus cells from the chronically inflamed ileum. In villus cell brush-border membrane vesicles from the chronically inflamed ileum, Na+-bile acid cotransport was also decreased, indicating a direct consequence of the cotransporter itself.

An in vitro model of adaptive cytoprotection caused by deoxycholate (DC) in human gastric cells was established. Protreatment with a low concentration of DC was found to substantially reduce injury caused by a damaging concentration of DC. The effect of DC as a mild irritant on changes in intracellular Ca2+ was evaluated. Findings showed that protection conferred by mild irritant was lost when any of its effects on intracellular Ca2+ were prevented.

A study was conducted on the mechanism responsible for the impaired modulation of hepatic cAMP formation after bile duct ligation (BDL). The findings indicate that cAMP stimulates both bile acid uptake and secretion. Therefore, impairment of cAMP synthesis and bile acid uptake may be an initial hepatocellular defense mechanism during cholestasis whereby bile acid accumulation in the hepatocyte is prevented.

Research was conducted to study influence of Na+-dependent transport mechanisms on the enterohepatic circulation of bile acids. Human ileum, cecum and kidney tissue samples were gathered from surgical specimens excised as a result of colon carcinoma, inflammatory bowel disease or kidney carcinoma. Results showed that the taurocholate uptake by human ileal Na+-bile acid cotransporter-transfected cells exhibit a strict condition for external Na+.

Research shows that taurocholate absorption in the ileum via ileal brush-border membrane vesicles is stimulated and controlled by glucocorticoids. Western blot analysis techniques demonstrate that more ileal bile acid transporter (iBAT) is transcribed under the influence of glucocorticoid. Glucocorticoids appear to play an important part in ileal bile acid uptake.

Fluorescent bile acid derivatives such as cholyl-NBDAB-Gly and chenodeoxycholyl-NBDAB-Gly were utilized to characterize the uptake of bile acid molecules during the synthesis of bile acids in rat liver. Analysis of the uptake of the two fluorescent bile acid derivatives in the hepatic bile duct of the rat liver indicated the presence of a carrier-mediated anion transport system that mediated the uptake of bile acid molecules. Furthermore, the carrier exhibited a broad specificity and due to its multiple transport functions.

The therapeutic effects of dietary treatments with bile acids were analyzed in the small intestines of rats subjected to prolonged dietary bile acid pretreatments. Administration of ursodeoxycholic acid (UDCA) enhanced the inhibitory effects of indomethacin on food intake and body weight. The stimulatory effects of indomethacin on the biliary contents of secondary bile acids and gross inflammatory scores in rat small intestines was also enhanced by UDCA. On the other hand, tauroursodeoxycholic acid inhibited the effects of indomethacin on the biliary contents of secondary bile acids.

Biliary glutathione (GSH) efflux was measured in rats with streptozotocin (STZ)-induced diabetes to determine changes in hepatic GSH transport due to diabetes. Rats with STZ-induced diabetes exhibited significant alterations in hepatobiliary metabolism such as progressive and significant reductions in bile GSH output due to heightened protein kinase C levels. However, canalicular GSH transport was not affected STZ-induced diabetes in rats.

The role of intracellular membrane systems in the delivery of bile salts to the canalicular membrane for secretion was analyzed in rat hepatocyte couplets by confocal scanning fluorescence microscopy (CSFM). CSFM analysis of cellular and canalicular fluorescence from rat hepatocyte couplets indicated the simultaneous occurrence of bile salts across the canalicular membrane and intracellular structures. Furthermore, the dependence of hepatic bile salt secretion on microtubule-dependent vesicle trafficking was indirect and involved the insertion and retrieval of transport proteins.

The mechanisms of estrogen-cholestasis after chronic ethinyl estradiol administration were analyzed in male Sprague-Dawley (SD) rats based on the quantitative analysis of taurochlorate uptake and membrane transport. Taurochlorate transport, Na+-K+-adenosine triphosphatase activity and sinusoidal membrane fluidity was impaired by 13% in SD rats after the administration of ethinyl estradiol. The marked reduction in membrane bile acid transport was also mediated by low bile acid transporter protein mass and decreased Na+ gradient driving forces in the lipid membrane.