Pleiotropic Functions of the Organic Solute Transporter Ostα-Ostβ

Abstract

tor and the vitamin D receptor, are ligands for a G-proteincoupled bile acid receptor (GPBAR1/TGR5), and can also activate protein kinases A and C as well as mitogen-activated protein kinase pathways. These signaling pathways are present in many tissues and regulate processes such as triglyceride, glucose and energy homeostasis. Note that although FXR and TGR5 are thought to function primarily as bile acid receptors, they are modulated by some other sterols and select lipid metabolites, and are also widely expressed in tissues, indicating a complex interplay among diverse regulatory networks that impact critical cell and organ functions. The present report summarizes the evidence for a pleiotropic role of Ost ␣ -Ost ␤ in different tissues.

The heteromeric organic solute transporter, OSTα–OSTβ/SLC51: A transporter for steroid-derived molecules

“…OSTα–OSTβ can also transport other signaling molecules, including estrone 3-sulfate, PREGS, DHEAS and prostaglandin E 2 (Ballatori et al, 2008; Fang et al, 2010; Wang et al, 2001). The localization of OSTα–OSTβ to steroidogenic tissues such as the ovary, testis, uterus, mammary gland, prostate, thyroid, and adrenal gland, and steroidogenic cells in the brain supports additional roles for this transporter (Fang et al, 2010; Seward et al, 2003; Ballatori, 2011). …”

“…Additional evidence for a role of the transporter in bile acid disposition comes from the observation that OSTα–OSTβ tissue distribution pattern overlaps that of the farnesoid X receptor (FXR) and of TGR5/GPBAR1, both bile acid receptors (Ballatori, 2011). FXR expressed sequence tag counts are quite abundant in human adrenal gland, are expressed at relatively high levels in the intestine, kidney, liver, and mammary gland, and are also detected in ovary, blood, brain, and connective tissue (Ballatori, 2011).…”

“…FXR expressed sequence tag counts are quite abundant in human adrenal gland, are expressed at relatively high levels in the intestine, kidney, liver, and mammary gland, and are also detected in ovary, blood, brain, and connective tissue (Ballatori, 2011). …”

“…OSTα–OSTβ also appears to have effects outside of the digestive tract (Ballatori, 2011). Bile acids are decreased in serum of Slc51a -deficient mice, indicating that OSTα–OSTβ is important for maintaining systemic bile acid levels and that it may have effects on other tissues (Ballatori et al, 2008).…”

β-Subunit of the Ostα-Ostβ Organic Solute Transporter Is Required Not Only for Heterodimerization and Trafficking but Also for Function

“…The heteromeric organic solute transporter (Ost) 2 ␣-␤ (Ost␣-Ost␤/Slc51) is the key basolateral plasma membrane bile acid and steroid conjugate carrier in many human tissues, including the small intestine, liver, and other steroidogenic organs (1)(2)(3)(4). Recently, Ost␣ Ϫ/Ϫ mice have been generated (5-7), and these animals exhibit a major defect in intestinal bile acid absorption, confirming that Ost␣-Ost␤ is the main intestinal bile acid efflux transporter in the enterohepatic circulation.…”