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

Francis R. Simon, John Fortune, Mieko Iwahashi, Susan Bowman, Allan W. Wolkoff, Eileen Sutherland

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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 α-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume276
Issue number2 39-2
StatePublished - 1999

Fingerprint

Taurocholic Acid
Liver
Organic Anion Transporters
Hepatocytes
Membrane Fluidity
Membrane Lipids
Peptides
Anions
Sodium
Fluorescence Polarization
Cholesterol Esters
Bile Acids and Salts
Phosphatidylcholines
Estrogens
Lipids
Messenger RNA
Membranes

Keywords

  • Lipid composition
  • Lipid fluidity
  • Organic anion transport peptide
  • Sodium-dependent taurocholate transporter
  • Transcription

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Characterization of the mechanisms involved in the gender differences in hepatic taurocholate uptake. / Simon, Francis R.; Fortune, John; Iwahashi, Mieko; Bowman, Susan; Wolkoff, Allan W.; Sutherland, Eileen.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 276, No. 2 39-2, 1999.

Research output: Contribution to journalArticle

Simon, Francis R. ; Fortune, John ; Iwahashi, Mieko ; Bowman, Susan ; Wolkoff, Allan W. ; Sutherland, Eileen. / Characterization of the mechanisms involved in the gender differences in hepatic taurocholate uptake. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 1999 ; Vol. 276, No. 2 39-2.
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