Characterization of the mechanisms involved in the gender differences in hepatic taurocholate uptake

Am J Physiol. 1999 Feb;276(2):G556-65. doi: 10.1152/ajpgi.1999.276.2.G556.


Gender differences in the hepatic transport of organic anions is well established. Although uptake of many organic anions is greater in females, sodium-dependent taurocholate uptake is greater in hepatocytes from male rats. We examined the hypothesis that endogenous estrogens alter the number of sinusoidal bile acid transporters and/or decrease membrane lipid fluidity. The initial sodium-dependent uptake of [3H]taurocholate was 75% greater in hepatocytes from males than from either intact or oophorectomized females rats. Taurocholate maximal uptake was increased twofold (P < 0.03) without a significant change in the Michaelis-Menten constant. Sinusoidal membrane fractions were isolated from male and female rat livers with equal specific activities and enrichments of Na+-K+-ATPase. Males had a significant (P < 0.05) increase in cholesterol esters and phosphatidylethanolamine-to-phosphatidylcholine ratio. Fluorescence polarization indicated decreased lipid fluidity in females. In females, expression of the sodium-dependent taurocholate peptide (Ntcp) and mRNA were selectively decreased to 46 +/- 9 and 54 +/- 4% (P < 0.01), respectively, and the organic anion transporter peptide (Oatp) and Na+-K+-ATPase alpha-subunit were not significantly different. Nuclear run-on analysis indicated a 47% (P < 0.05) decrease in Ntcp transcription, without a significant change in Oatp. In conclusion, these studies demonstrated that decreased sodium-dependent bile salt uptake in female hepatocytes was due to decreased membrane lipid fluidity and a selective decrease in Ntcp.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anion Transport Proteins
  • Aryl Hydrocarbon Hydroxylases*
  • Biological Transport / physiology
  • Carrier Proteins / genetics
  • Cytochrome P-450 Enzyme System / genetics
  • Female
  • Liver / metabolism*
  • Male
  • Membrane Fluidity / physiology
  • Membrane Lipids / chemistry
  • Membrane Lipids / physiology
  • Membrane Proteins / analysis
  • Membrane Transport Proteins*
  • Organic Anion Transporters, Sodium-Dependent
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sex Characteristics*
  • Steroid Hydroxylases / genetics
  • Symporters
  • Taurocholic Acid / pharmacokinetics*


  • Anion Transport Proteins
  • Carrier Proteins
  • Membrane Lipids
  • Membrane Proteins
  • Membrane Transport Proteins
  • Organic Anion Transporters, Sodium-Dependent
  • RNA, Messenger
  • Symporters
  • sodium-bile acid cotransporter
  • Taurocholic Acid
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • Aryl Hydrocarbon Hydroxylases
  • steroid 15-beta-hydroxylase