Effect of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on the Expression of Luteinizing Hormone Receptors during Cell Differentiation in Cultured Granulosa Cells

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is a common environmental pollutant causing public concern. By use of a cell culture system derived from rat granulosa cells that provides unique advantages for studying the molecular mechanisms underlying the action of TCDD, the influence of TCDD on luteinizing hormone receptor (LHR) induction was examined. Treatment with follicle-stimulating hormone (FSH) produced, as expected, a substantial increase in specific LHR expression; concurrent treatment with TCDD (10 pM) resulted in a significant decrease in LHR after 24 h. Cotreatment with 30 ng/ml FSH and increasing doses of TCDD inhibited the levels of FSH-induced LHR mRNA in a dose-dependent manner, and 1 pM TCDD inhibited FSH-induced LHR significantly after 48 h. The rate of LHR mRNA gene transcription, assessed by nuclear run-on transcription assay, was found to decrease after addition of TCDD. The decay curves for the 5.4-kb LHR mRNA transcript showed a significant decrease after addition of TCDD.