REACTIVE HUMAN BILE DUCTULES EXPRESS PARATHYROID HORMONE-RELATED PEPTIDE

Various cholestatic liver diseases as well as regeneration after subma ssive necrosis are accompanied by a striking increase in the number of bile ductules. These reactive bile ductules are thought to arise eith er from proliferation of pre-existing bile ductules or bile ductule-re lated facultative stem cells, or from ductular metaplasia of hepatocyt es. Recently, we found that reactive bile ductules display neuro-endoc rine features, and speculated that the substance(s), produced in the n euro-endocrine granules, might play a role in their growth and/or diff erentiation through an autocrine or paracrine pathway. Parathyroid hor mone-related peptide has been shown to be encoded by a growth factor-r egulated gene that may play a role in cell growth and differentiation. We studied the immunohistochemical expression of this peptide in huma n liver, including three normal biopsies, 11 cases of cholestatic live r disease, six cases of focal nodular hyperplasia and three cases of r egenerating liver. In regenerating liver, primary biliary cirrhosis, p rimary sclerosing cholangitis and partial or intermittent obstruction, the majority of reactive ductular cells expressing neuro-endocrine ma rkers also expressed parathyroid hormone-related peptide. In focal nod ular hyperplasia, a smaller number of bile ductular cells expressed th e peptide. These findings suggest that parathyroid hormone-related pep tide is localized in bile ductular cells and may indicate a role for t his hormone in the growth and/or differentiation of human reactive bil e ductules.