Elevated hepatic SULT1E1 activity in mouse models of cystic fibrosis alters the regulation of estrogen responsive proteins

J Cyst Fibros. 2007 Jan;6(1):23-30. doi: 10.1016/j.jcf.2006.05.001. Epub 2006 Jun 23.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / physiopathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / analysis
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Disease Models, Animal
  • Estradiol / metabolism*
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / metabolism
  • Estrogens / physiology
  • Hepatocytes / metabolism
  • Humans
  • Liver Diseases / etiology*
  • Liver Diseases / physiopathology
  • Mice
  • Mice, Inbred CFTR
  • Mice, Knockout
  • Sulfotransferases / analysis
  • Sulfotransferases / metabolism*


  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Estradiol
  • Sulfotransferases
  • estrone sulfotransferase