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Title: Elevated hepatic SULT1E1 activity in mouse models of cystic fibrosis alters the regulation of estrogen responsive proteins. Author: Li L, Falany CN. Journal: J Cyst Fibros; 2007 Jan; 6(1):23-30. PubMed ID: 16798114. Abstract: BACKGROUND: Previous studies with cystic fibrosis transmembrane conductance regulator (CFTR) DeltaF508 mice indicate that estrogen levels may play a role in the occurrence or severity of CF-associated liver disease. However, the underlying mechanisms of liver disease in CF are poorly understood. METHODS: The levels of SULT1E1 (estrogen sulfotransferase) were measured in livers of control and CFTR-knockout (KO) mice. The impact of increased SULT1E1 activity on hepatic protein expression was assessed by immunoblot and MALDI mass spectrometric analysis. RESULTS: SULT1E1 expression was significantly elevated in livers of several CFTR-KO mice. SULT1E1 and CFTR were specifically detected in hepatocytes and cholangiocytes, respectively. Elevated SULT1E1 activity may result in lower levels of free beta-estradiol thereby altering estrogen-responsive hepatic protein expression. Estrogen receptors (ER)-alpha and beta were differentially regulated in CFTR-KO and CFTR-DeltaF508 mice. ERalpha expression was reduced in mice with high SULT1E1 activity. Glutathione S-transferase-P1 and carbonic anhydrase III were significantly decreased in CFTR (-/-) mice with high SULT1E1 activity. Furthermore, cytochrome P450 2B9, also estrogen regulated, was significantly induced in the livers of CFTR (-/-) mice with high SULT1E1 activity. CONCLUSIONS: Elevated SULT1E1 levels and associated alterations in estrogen-regulated hepatic protein expression may play an important role in CF liver disease.[Abstract] [Full Text] [Related] [New Search]