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Gao, X.* ; Mizuyachi, K.* ; Terranova, P.F.* ; Rozman, K.K.

2,3,7,8-Tetrachlorodibenzo-p-dioxin decreases responsiveness of the hypothalamus to estradiol as a feedback inducer of preovulatory gonadotropin secretion in the immature gonadotropin- primed rat.

Toxicol. Appl. Pharmacol. 170, 181-190 (2001)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Sprague-Dawley rats (23-day-old) were dosed with TCDD (32 mug/kg) in corn oil or vehicle alone. Equine chorionic gonadotropin (eCG) was injected (5 IU, sc) 24 h later to induce follicular development. Another 24 h later, half of TCDD- or corn oil-treated rats were injected (sc) with 17 beta -estradiol-cypionate (ECP, at 0.004 to 0.5 mg/kg), Blood and ovaries were collected on expected proestrous (preovulatory period) at 51, 54, and 58 h after eCG injection as well as in the morning after ovulation (72 h after eCG), Serum concentrations of 17 beta -estradiol (E), progesterone (P), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined by radioimmunoassay, The number of ova shed was measured at 72 h after injection of eCG by irrigating ova from oviducts, During the preovulatory period (similar to 58 h after eCG injection), a circulating level of 70-100 pg E/ml coincided with LH and FSH surges and later normal ovulation of 10 to 12 ova/rat was observed in controls. However, the same concentration of E was not associated with LH and FSH surges in rats treated with TCDD (32 mug/kg), resulting in reduced ovarian weight gain and reduction of ovulation by 70 to 80% (2-3 ova/rat), Blockage of the gonadotropin surge, reduced ovarian weight gain, and ovulation were all reversed completely by the lowest effective dose of ECP (0.1 mg/kg), At 72 h after eCG, serum P secretion was reduced and serum E levels were significantly increased compared to those of corn oil-treated controls. ECP alone had no effect on serum P levels at any time point, but in rats treated with TCDD and ECP, both the reduction of P (at 58 and 72 h) and the increase in E secretion (72 h) were completely reversed. Further studies confirmed that restoration by ECP of gonadotropin surges and associated ovulation could not be attained until circulating levels of E rose sufficiently high to trigger the LH and FSH surges. The new action threshold of E for inducing gonadotropin surges in rats treated with TCDD (32 mug/kg) was determined to be eight- to 10-fold higher than that in controls. Thus, it is apparent that TCDD decreased the responsiveness of the hypothalamus to E as a feedback inducer of preovulatory gonadotropin secretion.
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Publication type Article: Journal article
Document type Scientific Article
Keywords DIBENZO-P-DIOXINS; IN-UTERO; LACTATIONAL EXPOSURE; HYDROCARBON RECEPTOR; OVULATION MODEL; HOLTZMAN RATS; TCDD; MODULATION; EXPRESSION; TOXICITY
Language english
Publication Year 2001
HGF-reported in Year 0
ISSN (print) / ISBN 0041-008X
e-ISSN 1096-0333
Quellenangaben Volume: 170, Issue: 3, Pages: 181-190 Article Number: , Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
PubMed ID 11162783
Scopus ID 0035251424
Erfassungsdatum 2002-03-07