ET-1 affected steroidogenesis in the present MDS study. A previous study using a rat granulosa cell culture showed a direct action of ET-1 on steroidogenesis. This action involves selective modulation of key steroidogenic steps concerned with formation and degradation of steroids: ET-1 attenuates enzymatic action common to P4 and A production, such as that of cholesterol side-chain cleavage and 3p-hydroxysteroid dehydrogenase (3p-HSD), but increases the activity of those enzymes that participate in their degradation (5a-reductase and 3p-HSD). Indeed, ET-1 also inhibited the release of P4 and A from the bovine ovary in the present MDS study. In contrast, E2 release was stimulated by ET-1 for a prolonged period, suggesting that ET-1 may stimulate aromatase activity. Although the effect of ET-1 on the release of E2 in the MDS might be through an indirect pathway, a direct stimulatory effect of ET-1 on the E2 secretion is also highly possible. ventolin inhaler
Specifically, some of the ET-1 infused into the MDS may pass through the theca interna into the granulosa cell layer, so that it may directly stimulate the E2 secretion from granulosa cells. This would be a better explanation for the opposite effects of ET-1 on P4 and A secretion (inhibition) and E2 secretion (stimulation) that were observed in the present study. Moreover, ET-1 stimulated PGE2 release in this study. ET-1 has been shown to activate multiple biochemical pathways within the target cells including phospholipase C, phospholipase D, and the arachidonate cascade. Theca cells as well as endothelial cells and granulosa cells could be responsive to such activations, since all these cell types are capable of PGE2 production (our unpublished results).