Differential regulation of soluble epoxide hydrolase by clofibrate and sexual hormones in the liver and kidneys of mice

Franck Pinot, David F. Grant, Jimmy L. Spearow, Anthony G. Parker, Bruce D. Hammock

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Soluble epoxide hydrolase (sEH) activity was measured in the liver and kidneys of male, female, and castrated male mice in order to evaluate sex- and tissue-specific differences in enzyme expression. sEH activity was found to be higher in liver than in kidneys. Activity increased with age in the liver of females, males and castrated males, but only in males did activity in the kidneys increase. There was greater activity in both the liver and kidneys of adult males than females. This sexual dimorphism was more pronounced in the kidneys (283% higher) than in the liver (55% higher). Castration of males led to a decrease in activity in both organs, but it had a greater effect on renal activity (67% decrease) than on hepatic activity (27% decrease). Treatment of castrated mice with testosterone led to an increase in sEH activity of 400% in kidneys and 49% in liver compared with surgical controls. These results suggest differential regulation of sEH by testosterone in kidneys and liver. Ovariectomized female mice had renal and hepatic activities approximately 30% greater than control females. Feeding mice with the hypolipidemic drug clofibrate produced stronger induction of sEH in liver than in kidneys. Testosterone treatment, however, caused greater induction in kidneys than in liver of females and castrated males and had no effect in either kidneys or liver in males. When given together, the effects of these two compounds appeared to be additive in both liver and kidneys. Results from western blot showed that the increase in sEH enzyme activity in kidneys is correlated with an increase in sEH protein. These results suggest that clofibrate and testosterone independently regulate sEH activity in vivo, and that kidneys and liver respond differently to clofibrate and testosterone.

Original languageEnglish (US)
Pages (from-to)501-508
Number of pages8
JournalBiochemical Pharmacology
Volume50
Issue number4
DOIs
StatePublished - Aug 8 1995

Fingerprint

Epoxide Hydrolases
Clofibrate
Liver
Hormones
Kidney
Testosterone
Hypolipidemic Agents
Enzyme activity
Orchiectomy
Enzymes

Keywords

  • clofibrate
  • hormones
  • induction
  • peroxisome proliferators
  • regulation
  • soluble epoxide hydrolase

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Differential regulation of soluble epoxide hydrolase by clofibrate and sexual hormones in the liver and kidneys of mice. / Pinot, Franck; Grant, David F.; Spearow, Jimmy L.; Parker, Anthony G.; Hammock, Bruce D.

In: Biochemical Pharmacology, Vol. 50, No. 4, 08.08.1995, p. 501-508.

Research output: Contribution to journalArticle

Pinot, Franck ; Grant, David F. ; Spearow, Jimmy L. ; Parker, Anthony G. ; Hammock, Bruce D. / Differential regulation of soluble epoxide hydrolase by clofibrate and sexual hormones in the liver and kidneys of mice. In: Biochemical Pharmacology. 1995 ; Vol. 50, No. 4. pp. 501-508.
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