TCDD increases inhibin A production by human luteinized granulosa cells in vitro

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic of the halogenated dioxins and one of the most poisonous substances known to man. The major toxic effects of TCDD on reproduction are decreased fertility and diminished ability to maintain a pregnancy. Granulosa cells obtained from hormonally stimulated women participating in an in-vitro fertilization program were cultured with 3.1 femtomolar, 3.1 picomolar and 3.1 nanomolar TCDD. While inhibin B production was not altered, inhibin A production increased significantly after 4 hours of exposure to both nanomolar and micromolar TCDD concentrations. By 8 hours of exposure to these concentrations of dioxin, human luteinizing granulosa cells exhibited a pronounced increase in inhibin A, nearly quadrupling secretion from unexposed control cells. TCDD continued to increase inhibin A secretion at the picomolar concentration at 24 and 36 hours. It is conceivable that TCDD may act at the ovary to augment inhibin A secretion, thereby reducing FSH-stimulable estrogen secretion by granulosa cells.