The methoxychlor metabolite, HPTE, inhibits rat luteal cell progesterone production

Yucel Akgul, Raymond C. Derk, Terence Meighan, K. Murali Krishna Rao, Eisuke P. Murono

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The methoxychlor metabolite, HPTE, was shown to inhibit P450-cholesterol side-chain cleavage (P450scc) activity resulting in decreased progesterone production by cultured ovarian follicular cells in previous studies. It is not known whether HPTE has any effect on progesterone formation by the corpus luteum. Results: Exposure to 100. nM HPTE reduced progesterone production by luteal cells with progressive declines to <22% of control at 500. nM HPTE. Similarly, HPTE progressively inhibited progesterone formation and P450scc catalytic activity of hCG- or 8 Br-cAMP-stimulated luteal cells. However, HPTE did not alter mRNA and protein levels of P450scc. Compounds acting as estrogen (17β-estradiol, bisphenol-A or octylphenol), antiestrogen (ICI) or antiandrogen (monobutyl phthalate, flutamide or M-2) added alone to luteal cells did not mimic the action of HPTE on progesterone and P450scc activity. These results suggest that HPTE directly inhibits P450scc catalytic activity resulting in reduced progesterone formation, and this action was not mediated through estrogen or androgen receptors.

Original languageEnglish (US)
Pages (from-to)77-84
Number of pages8
JournalReproductive Toxicology
Volume32
Issue number1
DOIs
Publication statusPublished - Jul 1 2011

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Keywords

  • Cholesterol side-chain cleavage
  • HPTE
  • Luteal cells
  • Methoxychlor
  • Ovarian steroidogenesis
  • P450scc

ASJC Scopus subject areas

  • Toxicology

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