Pharmacokinetics of ovarian steroids in Sprague-Dawley rats after acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces abnormalities in steroid-dependent processes such as mammary cell proliferation, gonadotropin release and maintenance of pregnancy. In the current study, the effects of TCDD on the pharmacokinetics of 17beta-estradiol and progesterone were examined. Adult Sprague-Dawley rats were ovariectomized and pretreated with TCDD (15 microg/kg p.o.) or vehicle. A single bolus of 17beta-estradiol (E2, 0.3 micromol/kg i.v.) or progesterone (P4, 6 micromol/kg i.v.) was administered 24 hours after TCDD and blood was collected serially from 0-72 hours post-injection. Intravenous E2 and P4 in DMSO vehicle had elimination half-lives of approximately 10 and 11 hours, respectively. TCDD had no significant effect on the pharmacokinetic parameters of P4. The elimination constant and clearance of E2 were decreased by TCDD while the elimination half-life, volume of distribution and area under the time*concentration curve were not altered significantly. Overall, these results indicate that diminished serum progesterone and estradiol concentrations following exposure to TCDD are due primarily to actions on steroid synthesis and release rather than any alterations in pharmacokinetics.
Petroff
Brian K
BK
Center for Reproductive Sciences, Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. bpetroff@kumc.edu
Mizinga
Kemmy M
KM
D000818:Animals; D004347:Drug Interactions; D004958:Estradiol / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D010052:Ovariectomy; D010053:Ovary / Q000187:drug effects / Q000502:physiology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011374:Progesterone / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000494:pharmacology*
D000072317:Polychlorinated Dibenzodioxins; D013723:Teratogens; D011374:Progesterone; D004958:Estradiol