Induction of rabbit lung CPY4A4 prostaglandin ω-hydroxylase by various steroid hormones

T. J. McCabe, L. J. Roman, B. S S Masters

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Cytochrome P4504A4 (CYP4A4) is expressed at low basal levels in adult rabbit lungs, but is significantly induced during pregnancy by an unknown mechanism. As the gradual rise in CYP4A4 leveis appears to coincide with the progressive increase in several steroid hormones throughout pregnancy, we examined the induction of CYP4A4 after treatment with various steroid hormones by monitoring both the CYP4A4 mRNA level and the CYP4A4-specific prostaglandin E1 (PGE1) ω-hydroxylation reaction in rabbit lung microsomes. Treatment with progesterone and/or a synthetic glucocorticoid (dexamethasone) resulted in a significant increase in PGE1 ω-hydroxylase activity, whereas estradiol, aldosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate did not. These studies indicated that dexamethasone was a more potent inducer of CYP4A4 than progesterone. Simultaneous injection of dexamethasone and glucocorticoid/progesterone antagonists (RU38486, RU40555, or RU43044) inhibited the increase in PGE1 ω-hydroxylase activity as well as mRNA levels by approximately 50%. In addition, simultaneous treatment with both dexamethasone and progesterone did not result in an additive or synergistic effect on PGE1 ω-hydroxylase activity. These data indicate that, while distinctive receptors for glucocorticoid and/or progesterone are involved, induction may also require common or interacting regulatory elements (yet to be determined) in the CYP4A4 gene. These findings implicate both of these steroid receptors (PR/GR) in the induction of CYP4A4 in rabbit lung.

Original languageEnglish (US)
Pages (from-to)78-86
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume393
Issue number1
DOIs
StatePublished - Sep 1 2001

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Steroid Hydroxylases
Steroid hormones
Cytochromes
Prostaglandins
Hormones
Rabbits
Lung
Alprostadil
Dexamethasone
Progesterone
Mixed Function Oxygenases
Glucocorticoids
Steroids
Pregnancy
Hydroxylation
Messenger RNA
Dehydroepiandrosterone Sulfate
Dehydroepiandrosterone
Steroid Receptors
Glucocorticoid Receptors

Keywords

  • ω-hydroxylation
  • CYP4A4
  • Cytochrome P450
  • Prostaglandin
  • Steroid receptor
  • Steroid receptor antagonists

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Induction of rabbit lung CPY4A4 prostaglandin ω-hydroxylase by various steroid hormones. / McCabe, T. J.; Roman, L. J.; Masters, B. S S.

In: Archives of Biochemistry and Biophysics, Vol. 393, No. 1, 01.09.2001, p. 78-86.

Research output: Contribution to journalArticle

McCabe, T. J. ; Roman, L. J. ; Masters, B. S S. / Induction of rabbit lung CPY4A4 prostaglandin ω-hydroxylase by various steroid hormones. In: Archives of Biochemistry and Biophysics. 2001 ; Vol. 393, No. 1. pp. 78-86.
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