Glucocorticoids upregulate taurocholate transport by ileal brush-border membrane

Area of Science:

• Biochemistry
• Physiology
• Molecular Biology

Background:

• The enterohepatic circulation of bile acids is crucial for digestion but its regulation is not fully understood.
• Ileal uptake of taurocholate (TC) is known to be regulated by substrate availability via positive feedback.
• Additional regulatory mechanisms for ileal bile acid uptake are likely involved.

Purpose of the Study:

• To investigate whether the ileal bile acid transporter (iBAT) is sensitive to glucocorticoids.
• To determine if changes in iBAT expression are mediated by alterations in iBAT synthesis.

Main Methods:

• Adult rats were administered corticosterone or a vehicle control daily for 3 days.
• Ileal brush-border membrane vesicles (BBMV) and hepatic basolateral membrane vesicles (BLMV) were isolated.
• Taurolicholate (TC) transport kinetics, iBAT mRNA levels (Northern analysis), and iBAT protein abundance (Western blot) were assessed.

Main Results:

• Na(+)-dependent TC uptake velocity and maximal velocity (Vmax) in ileal BBMV were significantly higher in corticosterone-treated rats compared to controls.
• Steady-state iBAT mRNA levels increased twofold, and 48-kDa iBAT protein abundance increased eightfold in treated animals.
• Hepatic TC uptake kinetics showed no significant differences between treated and control groups.

Conclusions:

• Glucocorticoid administration upregulates taurocholate (TC) transport in the ileum.
• The increased ileal BBMV transport Vmax is associated with elevated iBAT mRNA and protein levels.
• These findings suggest that glucocorticoids regulate bile acid absorption through modulation of iBAT expression.