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 environmenta l 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 o n luteinizing hormone receptor (LHR) induction was examined. Treatment with follicle-stimulating hormone (FSH) produced, as expected, a substantial in crease in specific LHR expression; concurrent treatment with TCDD (10 pM) r esulted 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 LH R 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 additio n of TCDD. The decay curves for the 5.4-kb LHR mRNA transcript showed a sig nificant decrease after addition of TCDD. (C) 2000 Academic Press.