Hepatic cysts are a common manifestation of autosomal dominant polycystic kidney disease (ADPKD). Recent studies from our laboratory suggest that hepatic cystic disease is modulated by female gender, number of pregnancies, and use of female steroid hormones. In addition, secretion by hepatic cysts may be stimulated by secretin. We have recently obtained hepatic cystic tissue from resected livers of patients with ADPKD, transferred hepatic cysts to tissue culture, and grown them in defined media. Thus, the specific aim of the proposed project is to determine whether female steroid hormones influence the growth of hepatic cystic epithelia and whether secretin, or related hormones, stimulate secretion. Growth of hepatic cystic epithelium in response to hormones will be determined by cell counts as well as incorporation of radiolabeled thymidine. The effects of hormones will also be assessed by histologic, morphometric, and electron microscopic studies. Certain hormone receptors (estrogen, progesterone, glucocorticoid, and insulin) will be measured and correlated with growth in response to added hormones. Secretion by hepatic cystic epithelium in response to secretin and related peptides will be determined by measurement of cyclic-AMP basally and after exposure of cells to hormone. Immunohistochemical studies of secretory component, asialoglycoprotein receptor, leucine aminopeptidase, and lectins (PNA, DBA) which bind to biliary-type antigens will establish the similarity of polycystic epithelium to biliary epithelium. These studies represent the first attempt to culture and characterize hepatic cystic epithelium. The nature of hormonal regulation of hepatic cyst growth and secretion may be defined, and the results may provide a rationale for pharmacotherapy of hepatic cystic disease. In addition, these studies will determine whether hepatic cystic epithelium is functionally related to biliary epithelium. If the latter is true, hepatic cystic epithelium cells may serve as a proliferating cell culture model of biliary epithelium.
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