The 3alpha-hydroxy-steroid-dehydrogenase-mRNA and -protein are more prevalent in pericentral than in periportal hepatocytes.

Abstract

Under physiological conditions, de-novo synthesis and metabolism of bile acids are confined mainly to the pericentral zone of the liver acinus. In the rat, 3alpha-hydroxy-steroid-dehydrogenase (3alpha-HSD) is the major bile acid-binding protein. At the same time, this protein is involved in the de-novo synthesis and metabolism of bile acids. Because bile acid processing is greater in the pericentral than in the periportal region, we investigated whether 3alpha-HSD is more prevalent in the pericentral than in the periportal area. We determined the 3alpha-HSD-protein and its mRNA in periportal and pericentral rat cells. Rat hepatocytes from the periportal or pericentral areas were isolated using the digitonin perfusion technique. For Northern blotting, a labelled 1.3-kb cDNA insert corresponding to the mRNA sequence of 3alpha-HSD was used. For Western blotting, a polyclonal rabbit antiserum against human 3alpha-HSD was used. Blots were quantified by densitometry using phosphoimaging. The amounts of the 3alpha-HSD-protein and its mRNA were significantly greater in the pericentral than in the periportal cells. The greater occurrence of 3alpha-HSD in pericentral than in periportal hepatocytes is in line with the concept that bile acid synthesis and metabolism take place predominantly in pericentral cells.