Alterations to the pituitary-gonadal axis in the peripubertal female rat exposed in utero and through lactation to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) is a potent disrupter of vertebrate endocrine systems. It was shown previously that in utero and lactational (IUL) exposure to TCDD resulted in a reduction in serum estradiol concentrations; however, the mechanism for this remains unknown. In the current study, the effects of perinatal exposure to TCDD on the pituitary-ovarian axis were examined. Pregnant rats were given a single oral dose of 1 microg TCDD/kg or vehicle as control on gestation Day 15, and female pups were killed on postnatal Day 21. Pituitaries were assayed for gonadotropin beta-subunit mRNA; additional pituitaries were cultured for 4 h and the media were assayed for FSH. Gonadotropin receptor mRNAs from vehicle- and TCDD-exposed animals were compared, with some ovaries cultured and the media assayed for estrogen secretion. LH, FSH, progesterone, and androstenedione concentrations were determined in serum. IUL exposure to TCDD resulted in a significant reduction of pituitary FSHbeta mRNA. Although estrogen output was shown to be reduced, neither serum FSH nor LH concentration was increased significantly, and FSH secretion in vitro was not altered. Similarly, serum progesterone and androstenedione were not altered by TCDD exposure, while in vitro estrogen secretion was significantly reduced. These data suggest that TCDD did not act on serum gonadotropin concentrations. The reduction in the concentration of serum estrogen appears to result from direct or indirect actions on the ovary at some point following androstenedione production.