Pleiotropic Functions of the Organic Solute Transporter Ost-Ost

The heteromeric organic solute transporter alpha-beta (Ost -Ost ) is expressed at relatively high levels on the basolateral membrane of enterocytes, where it plays a critical role in the intestinal absorption of bile acids and the enterohepatic circulation. However, this transporter is also expressed in nearly all human tissues, including those that are not normally thought to be involved in bile acid homeostasis, indicating that Ost -Ost may have additional roles beyond bile acid transport in these other tissues, or that bile acids and their derivatives are more pervasive than currently envisioned. Emerging data from different laboratories provide support for both of these hypotheses. In particular, recent studies indicate that tissues such as brain and ovary have the capacity to synthesize bile acids or bile acid precursors. In addition, studies examining Ost -Ost substrate specificity have revealed that this transporter can also accept conjugated steroids, including some neurosteroids, and that the transporter is selectively expressed in steroidogenic cells of the brain and adrenal gland, suggesting a novel function for Ost -Ost . The broad tissue expression of Ost  -Ost is also consistent with the emerging concept that bile acids and their derivatives act as signaling molecules in diverse tissues. Bile acids activate nuclear receptors such as the farnesoid X receptor (FXR/NR1H4), the pregnane X recepNed Ballatori, PhD Department of Environmental Medicine, Box EHSC University of Rochester School of Medicine 601 Elmwood Avenue, Rochester, NY 14642 (USA) Tel. +1 585 275 0262, E-Mail Ned_Ballatori @ urmc.rochester.edu © 2011 S. Karger AG, Basel Accessible online at: www.karger.com/ddi D ow nl oa de d by : 54 .7 0. 40 .1 1 10 /3 1/ 20 17 7 :0 0: 59 P M