title: The methoxychlor metabolite, HPTE, inhibits rat luteal cell progesterone production.
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 (17 β-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.
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA. akgulyucel@gmail.com
authors.forename: Yucel
authors.initials: Y
authors.lastname: Akgul
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Derk
authors.forename: Terence
authors.initials: T
authors.lastname: Meighan
authors.forename: K Murali Krishna
authors.initials: KM
authors.lastname: Rao
authors.forename: Eisuke P
authors.initials: EP
authors.lastname: Murono
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D008184:Luteal Cells / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006063:Chorionic Gonadotropin; D004967:Estrogens; D010636:Phenols; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011374:Progesterone; D002786:Cholesterol Side-Chain Cleavage Enzyme; C404910:2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane