The inhibition of progesterone (P) formation of cultured ovarian theca interstitial (TI) cells by the methoxychlor (MC) metabolite, HPTE, is not mediated through the estrogen receptor (ER) or androgen receptor (AR).
Akgul-Y; Derk-RC; Murono-EP
Toxicologist 2007 Mar; 96(1):424
The pesticide MC is used on agricultural crops and livestock. MC exposure in rodents is linked to impaired steroid production, ovarian atrophy and reduced fertility. Following in vivo administration, it is rapidly converted to HPTE, reported active metabolite, by the liver. Both MC and HPTE have weak estrogenic and antiandrogenic activities, and these effects are thought to be mediated through the ER and ARs, respectively. Previous in vivo studies in female animals demonstrated decreased P production but no change in serum estrogen levels following exposure to MC. We showed a decrease in androgen and P production of follicular cells by HPTE in-vitro. The current studies examined the mechanism of actions of HPTE on P production by cultured ovarian TI cells from immature rats. To isolate TI cells, 24-25-day-old female Sprague-Dawley rats were injected (s.c.) with 20 I.U. of pregnant mare serum gonadotropin. Approximately 48 h following treatment, ovarian tissue was digested with collagenase and dispersed. TI cells were cultured in DMEM / F12 medium and exposed to HPTE for 24 h on the day of plating. Exposure to HPTE (0, 10, 50, 100 nM) alone inhibited P formation in a dose-dependent manner with a significant decline to ~12 % of control at 100 nM. In contrast, estrogens (estradiol, bisphenol-A, and 4-tert-octylphenol), pure anti-estrogen ICI 182,780 (ICI), and anti-androgens (4-OH-flutamide or the vinclozolin metabolite M-2) had no effect on P production even at 1000 nM. Co-treatment of HPTE with ICI did not block the effect of HPTE on P formation. These studies revealed that HPTE inhibition of P production by cultured TI cells is unique, and does not appear to be mediated through the ER or AR.
Physical-reactions; Risk-analysis; Risk-factors; Chemical-reactions; Toxic-effects; Chemical-hypersensitivity; Chemical-properties; Agricultural-chemicals; Agriculture; Agricultural-workers; Agricultural-industry; Pesticides-and-agricultural-chemicals; Animal-studies; In-vitro-studies; Cell-alteration; Cell-damage; Cell-metabolism; Cellular-reactions; Cellular-uptake; Humans; Fertility; Hormone-activity; Hormones; Dose-response
Agriculture, Forestry and Fishing; Manufacturing
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina