Comment

In May 1999 three papers were published which should change the way we think about bile acids.1-3 For long appreciated as detergents, important for micelle formation and lipid absorption in the intestine, they should now also be regarded as members of the steroid family of hormones, affecting transcriptional control of gene expression through a specific nuclear receptor, the farnesoid X receptor.

The primary bile acids (cholate and chenodeoxycholate) are synthesised from cholesterol in the liver with the enzyme cholesterol 7α-hydroxylase (CYP7A) being the rate-limiting step in the classic pathway. The activity of this enzyme has been known for some time to be under inhibitory feed-back control by bile acids.4 In view of the importance of this pathway in the removal of cholesterol, the mechanisms for the positive and negative regulation of transcription of the CYP7A gene have been studied.5 Until now, the mediator of the effects of bile acids had not been found.

In the ileum, conjugated bile salts are reabsorbed, undergoing an enterohepatic circulation. Again this pathway is regulated by the bile salts themselves. At the cellular level, bile acid absorption involves at least two specific carrier proteins. The ileal apical membrane sodium …