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Titolo:
Suppression of bile acid synthesis, but not of hepatic cholesterol 7 alpha-hydroxylase expression, by obstructive cholestasis in humans
Autore:
Bertolotti, M; Carulli, L; Concari, M; Martella, P; Loria, P; Tagliafico, E; Ferrari, S; Del Puppo, M; Amati, B; De Fabiani, E; Crestani, M; Amorotti, C; Manenti, A; Carubbi, F; Pinetti, A; Carulli, N;
Indirizzi:
Univ Studi Modena & Reggio Emilia, Dipartimento Med Interna, Div Med 3, Policlin, I-41100 Modena, Italy Univ Studi Modena & Reggio Emilia Modena Italy I-41100 100 Modena, Italy Univ Studi Modena & Reggio Emilia, Dipartimento Sci Biomed, I-41100 Modena, Italy Univ Studi Modena & Reggio Emilia Modena Italy I-41100 100 Modena, Italy Univ Studi Modena & Reggio Emilia, Dipartimento Sci Chirurg, I-41100 Modena, Italy Univ Studi Modena & Reggio Emilia Modena Italy I-41100 100 Modena, Italy Univ Studi Modena & Reggio Emilia, Dipartimento Chim, I-41100 Modena, Italy Univ Studi Modena & Reggio Emilia Modena Italy I-41100 100 Modena, Italy Univ Studi Milano Biococca, Dipartimento Med Sperimentale Ambientale & Biotec, Milan, Italy Univ Studi Milano Biococca Milan Italy mbientale & Biotec, Milan, Italy Univ Studi Milano, Ist Sci Farmacol, Milan, Italy Univ Studi Milano Milan Italy di Milano, Ist Sci Farmacol, Milan, Italy
Titolo Testata:
HEPATOLOGY
fascicolo: 2, volume: 34, anno: 2001,
pagine: 234 - 242
SICI:
0270-9139(200108)34:2<234:SOBASB>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
FEEDBACK-REGULATION; MESSENGER-RNA; RAT-LIVER; TRANSCRIPTIONAL ACTIVITY; DEOXYCHOLIC-ACID; METABOLISM; SERUM; SALTS; BIOSYNTHESIS; PATHWAYS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
59
Recensione:
Indirizzi per estratti:
Indirizzo: Bertolotti, M Univ Studi Modena & Reggio Emilia, Dipartimento Med Interna,Div Med 3, Policlin, Via Pozzo 71, I-41100 Modena, Italy Univ Studi Modena& Reggio Emilia Via Pozzo 71 Modena Italy I-41100
Citazione:
M. Bertolotti et al., "Suppression of bile acid synthesis, but not of hepatic cholesterol 7 alpha-hydroxylase expression, by obstructive cholestasis in humans", HEPATOLOGY, 34(2), 2001, pp. 234-242

Abstract

Regulation of bile acid synthesis, a key determinant of cholesterol homeostasis, is still incompletely understood. To elucidate the feedback control exerted on bile acid biosynthesis in humans with obstructive cholestasis, 16 patients with bile duct obstruction were studied. In vivo 7 alpha -hydroxylation, reflecting bile acid synthesis, was assayed in 13 of them by tritium release analysis. Serum 27-hydroxycholesterol was determined by gas chromatography-mass spectrometry. In a subgroup, hepatic cholesterol 7 alpha -hydroxylase mRNA was assayed by real-time polymerase chain reaction (PCR), enzyme activity was determined by isotope incorporation, and microsomal cholesterol content was assayed by gas chromatography-mass spectrometry. Age-matched control subjects were studied in parallel. Hydroxylation rates were lower in cholestatic patients (108 +/- 33 mg of cholesterol per day, mean +/- SEM; controls: 297 +/- 40 mg/d; P < .01). The reduction was proportional to the severity of cholestasis, and synthetic rates were normalized in 4 subjects restudied after resolution of biliary obstruction. Consistent findings were obtained by analysis of serum 7 alpha -hydroxycholesterol levels. On the other hand, hepatic cholesterol 7 alpha -hydroxylase mRNA, microsomalenzyme activity, and cholesterol content tended to be increased in cholestasis. Finally, serum 27-hydroxycholesterol levels were slightly reduced in cholestatic subjects and were not related with the severity of the disease. Suppression of in vivo bile acid synthesis with no corresponding reductionin tissue 7 alpha -hydroxylase expression and activity is consistent with nontranscriptional, posttranslational levels of regulation; these may play a role in the feedback control of bile acid synthesis in particular conditions. Alteration of the alternate biosynthetic pathway seems unlikely according to the present data.

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Documento generato il 28/11/20 alle ore 03:47:06