Interaction of estradiol and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in an ovulation model: evidence for systemic potentiation and local ovarian effects

Immature rats were treated with estradiol cypionate, (ECP, 0, 0.1, 1, or 2 mg/kg s.c.) followed 24 h later by TCDD (0 or 10 microg/kg orally). Follicular development was induced with eCG 5 or 10 IU subcutaneously (s.c.)] followed by an ovulatory dose of hCG (10 IU s. c.). Inhibition of ovulation by TCDD was potentiated by ECP in hypophysectomized but not intact rats. Only hypophysectomized rats exposed systemically to TCDD and ECP exhibited weight loss. Pair feeding mimicked the combined effects of TCDD and ECP in hypophysectomized rats. In another experiment, intact rats received ECP s.c. (0 or 2 mg/kg) and TCDD into the ovarian bursa (0 or 250 ng). Another group of intact rats received TCDD orally (10 microg/kg) and ECP into the ovarian bursa (0 or 1.5 microg). Blockade of ovulation by systemic or local TCDD was alleviated by ECP pretreatment. Estrogen increased the systemic toxicity of TCDD in rats whereas antagonizing its direct ovarian effects.