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(308) TCDD INCREASES INHIBIN A PRODUCTION BY HUMAN LUTEINIZED GRANULOSA CELLS IN VITRO.
Ho, Heather1, Oshima, Kenichi2, Tompa, David1, Watanabe, Gen2, Taya, Kazuyoshi2, Strawn, Estil3, Rawlins, Richard4, Hutz, Reinhold1, 1 Department of Biological Sciences, Milwaukee, WI2 Tokyo University of Agriculture and Technology, Tokyo, JP3 Medical College of Wisconsin, Milwaukee, WI4 Rush Presbyterian St. Luke's Medical Center, Chicago, IL
ABSTRACT- 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent of the chlorinated dioxins. For this reason TCDD is used as a prototype molecule to study the toxicity of this class of chemicals. The major reproductive toxic effects of TCDD are decreased fertility and diminished ability to maintain a pregnancy. In rats treated in-utero and lactationally (IUL) with TCDD there is a decrease in circulating estradiol and all estradiol-induced effects. It has been shown that TCDD IUL exposure results in a decrease in serum estradiol concentrations. We have also shown that FSH beta-mRNA is inhibited with IUL TCDD exposure in the rat, but the mechanism remains unknown. In the present study we have investigated how hormone production in vitro is altered by TCDD exposure. Human luteinized granulosa cells were obtained from women undergoing in vitro fertilization. These cells were cultured with TCDD at 3.1 fM, 3.1 pM and 3.1 nM concentrations. The media were collected after 4 and 8 hours of exposure and were assayed for inhibin a and inhibin b by RIA. While inhibin b production was not altered, inhibin a production was increased significantly after 8 hours of exposure to both picomolar and nanomolar concentrations of TCDD. There was a four-fold increase in inhibin a production from control after 8 hours of exposure to TCDD. It is conceivable that TCDD may act at the ovary to augment inhibin a secretion, thereby reducing FSH-stimulable estrogen secretion by the granulosa cells. (Supported in part by NIH ES08342 and the Office of Research on Womens Health.)
KEY WORDS: TCDD, inhibin a , granulosa cells