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Bile acids and progesterone metabolites in intrahepatic cholestasis of pregnancy.

Abstract：

:The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) can be related to abnormalities in the metabolism and disposition of sex hormones and/or bile acids, determined by a genetic predisposition interacting with environmental factors. The total amount of oestrogens and progesterone circulating in the blood or excreted in the urine of ICP patients is similar to normal pregnancies. Thus, the search for the cause has been focused on abnormal hormone metabolites. The cholestatic potential of some D-ring oestrogen metabolites is supported by experimental and clinical data. Similar observations with regard to bile acids and progesterone metabolites are still scarce. This article reviews current knowledge in this field, including our own data. Bile acid synthesis appears to be reduced in patients with ICP, in whom primary conjugated bile acids are retained in blood. The major bile acid in blood and urine of these patients is cholic acid instead of chenodeoxycholic acid present in normal pregnancies. Hydroxylation and sulfation of bile acids are enhanced, while glucuronidation appears to be of lesser importance. The synthesis of progesterone appears unimpaired, while the profiles of progesterone metabolites in plasma and urine are different from normal pregnancies, with a larger proportion of mono- and disulfated metabolites, mainly 3alpha,5alpha isomers. Glucuronidated metabolites, however, are unchanged. With the administration of ursodeoxycholic acid (UDCA) to patients with ICP, pruritus and serum liver values are improved, the concentration of bile acids in blood is diminished and the proportion of their conjugated metabolites returned to normal. Simultaneously, the concentration of sulfated progesterone metabolites in blood and their urinary excretion are reduced. The serum levels of bile acids and progesterone metabolites before UDCA administration and their decrease during treatment do not correlate with each other. We propose that patients with ICP have a selective defect in the secretion of sulfated progesterone metabolites into bile and speculate that this may be caused by genetic polymorphism of canalicular transporter(s) for steroid sulfates or their regulation. Interaction with oestrogen metabolites and/or some exogenous compounds may further enhance the process triggering ICP in genetically predisposed individuals.

journal_name

Ann Med

journal_title

Annals of medicine

authors

Reyes H,Sjövall J

doi

10.3109/07853890009011758

subject

Has Abstract

pub_date

2000-03-01 00:00:00

pages

94-106

issue

eissn

0785-3890

issn

1365-2060

journal_volume

pub_type

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Bile acids and progesterone metabolites in intrahepatic cholestasis of pregnancy.