IN-UTERO AND LACTATIONAL EXPOSURE OF FEMALE HOLTZMAN RATS TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN - MODULATION OF THE ESTROGEN SIGNAL

The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) induces severe reproductive defects in male rats when exposur e occurs in utero and during lactation. Yet there is currently a pauci ty of information regarding the effects of this exposure paradigm in f emales. In the current study, we examine the effects of TCDD during fe tal and perinatal development on the estrogen-signaling system in peri pubertal female rats. Pregnant Holtzman rats were given 1 mu g/kg TCDD or vehicle control by gavage on gestational Day 15. Body weights were reduced, though not significantly, on postnatal Day 27. While ovarian and uterine wet weights were not increased by TCDD exposure, the perc entage of body weight attributed to the ovary was increased significan tly. Through use of ribonuclease protection and gel-shift assays, expo sed females were compared with nonexposed counterparts for estrogen re ceptor (ER) mRNA and DNA-binding activity in the following tissues: hy pothalamus, pituitary (mRNA only), uterus, and ovary. ER mRNA levels i ncreased in the hypothalamus, uterus, and ovary, and decreased in the pituitary. The results of the DNA-binding assays paralleled the mRNA r esults in the uterus, while DNA-binding activity was decreased in the hypothalamus and was unchanged in ovarian protein extracts. Circulatin g concentrations of estrogen were significantly lower in TCDD-exposed rats than in controls. These data suggest that the decrease in serum e strogen may be a cause of the alterations in ER mRNA; the changes in E R DNA-binding activity may indicate alterations in either translation or posttranslational receptor processing. Overall, this study shows th at TCDD may act systemically in this model, and these effects should n ot necessarily be characterized as antiestrogenic.