Endothelins inhibit FSH-mediated function via ETA receptors in cultured human granulosa-lutein cells.

Endothelins (ETs) are a family of vasoactive peptides involved in granulosa and luteal cell function in some animal species. However, the potential relevance of ETs in ovarian physiology remains unclear, and the direct action of the peptides in the human ovary has not been studied to date. Experiments were conducted to determine whether ET-1 and ET-3 could regulate the follicle stimulating hormone (FSH)-induced cell response in human granulosa-lutein cells in culture. The FSH-mediated cell rounding process was used as an indicator of cell response, as previously described (Lawrence et al., 1979). Forskolin, cholera toxin, 8-Br-cyclic AMP, isobutylmethylxanthine (IBMX), rolipram and FSH all stimulated similar cell morphological changes, indicating that the cell rounding process was mediated by cyclic AMP. Although ET-1 and ET-3 alone failed to alter cell shape, the FSH-induced cell response was totally inhibited by treatment with ET-1 (10(-10) mol/l) and ET-3 (10(-7) mol/l). In addition, treatment of the cells with BQ123, an antagonist of ET binding on ETA receptor subtype, totally prevented the inhibitory effects of ET-1 and ET-3 on the FSH-induced response. The data presented here show that human granulosalutein cells are a site of ET reception and action. Endothelins inhibit cyclic AMP-dependent FSH-mediated function and the ET(A) receptor participates in this effect.