The methoxychlor metabolite, HPTE, inhibits rat luteal cell progesterone production.
Akgul Y; Derk RC; Meighan T; Rao KMK; Murono EP
Reprod Toxicol 2011 Jul; 32(1):77-84
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 HFTE. 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 (17 beta-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.
Biological-agents; Biological-monitoring; Exposure-assessment; Laboratory-animals; Reproduction; Reproductive-effects; Reproductive-hazards; Reproductive-system-disorders;
Author Keywords: Methoxychlor; HPTE; Ovarian steroidogenesis; Cholesterol side-chain cleavage; P450scc; Luteal cells
Yucel Akgul, Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV