Endothelin-1 as a local ovarian regulator in porcine granulosa cells

This study was conducted to investigate whether endothelin-1 (ET-1) has direct effects on the functions of porcine granulosa cells harvested from small or medium follicles. Positive ET-1-like immunoreactivity (ET-1-LI) was observed in the cultured porcine granulosa cells, and Northern blot analysis demonstrated the expression of mRNA for prepro-ET-1 in these cells. The binding study showed the presence of a nonselective, single class of binding sites which predominantly included the subtype ETB. Increased ET-1-LI was detected in human follicular fluid obtained from the patients with stimulated ovarian cycles. ET-1 stimulated basal and follicle-stimulating hormone (FSH)-stimulated secretion of progesterone during short-term incubation (2 h), while it inhibited FSH- and human-chorionic-gonadotropin-stimulated accumulation of progesterone during long-term incubation (48 h) of immature or moderately mature granulosa cells. ET-1 significantly increased DNA synthesis in the cells. These biological actions were induced by ET-1, probably via a cAMP-protein kinase A pathway and intracellular calcium mobilization-protein kinase C pathway. The results suggest that ET-1 exerts autocrine/paracrine effects on porcine granulosa cell functions.