title: Influence of human serum albumin on the bile acid-mediated inhibition of liver microsomal type 1 11β-hydroxysteroid dehydrogenase.
abstract: The influence of human serum albumin (HSA) on the bile acid-mediated inhibition of liver microsomal type 1 11β-hydroxysteroid dehydrogenase (11β-HSD1) was studied in vitro. A rat liver microsomal fraction was prepared, and the 11β-HSD1 enzyme activity in the presence of various concentrations of bile acids and HSA was determined using hydrocortisone as the substrate. The products of the reaction were extracted and analyzed using high-performance liquid chromatography. The magnitude of the inhibition decreased with the addition of HSA in a dose-dependent manner. Four percent human albumin decreased the inhibitory effects of 100 μM chenodeoxycholic acid and lithocholic acid from 89.9 ± 5.6 to 54.5 ± 6.1% and from 83.8 ± 4.8 to 20.8 ± 4.2%, respectively. In contrast, ursodeoxycholic acid and deoxycholic acid showed no inhibitory effect on the enzyme activity in the presence of 4% human serum albumin, and the addition of 1% γ-globulin to the assay mixture in the presence of bile acids did not affect the enzyme activity. Our in vitro study showed that the addition of HSA ameliorated the inhibition of 11β-HSD1 and that the magnitude of the change is dependent on the species of bile acid, presumably based on the numbers of hydroxyl groups. These results suggest that HSA seems to protect the bile acid-mediated inhibition of 11β-HSD1 in the healthy subject. On the other hand, in the patients with obstructive biliary diseases, not only elevated serum bile acid but also the accompanying hypoalbuminemia is important to evaluate the pathophysiology of the bile acid-mediated inhibition of 11β-HSD1 of the disease.
authors.affiliation: Department of Surgery, Brestopia Hospital, Maruyama 2-112-1, Miyazaki, 880 0052, Japan, y.maeda@breastopia.org.
authors.forename: Yorio
authors.initials: Y
authors.lastname: Maeda
authors.forename: Mayumi
authors.initials: M
authors.lastname: Funagayama
authors.forename: Akio
authors.initials: A
authors.lastname: Shinohara
authors.forename: Chihiro
authors.initials: C
authors.lastname: Koshimoto
authors.forename: Hidemi
authors.initials: H
authors.lastname: Furusawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakahara
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Saitoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kansei
authors.initials: K
authors.lastname: Komaki
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D019826:Cholic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008095:Lithocholic Acid / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism*; D014580:Ursodeoxycholic Acid / Q000494:pharmacology
chemical_list: D001647:Bile Acids and Salts; D012709:Serum Albumin; D002635:Chenodeoxycholic Acid; D008095:Lithocholic Acid; D014580:Ursodeoxycholic Acid; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D019826:Cholic Acid
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