Paradoxical effect of a GnRH agonist on steroidogenesis in cultured monkey granulosa cells.

In this study we demonstrate: (i) The GnRH agonist exerts a direct dose-dependent stimulative effect on the aromatase activity and progesterone production in cultured monkey granulosa cells; (ii) the stimulative effect on steroidogenesis can be completely blocked by concomitant treatment with a GnRH antagonist, suggesting that the actions of GnRH are mediated through stringent stereospecific recognition sites; (iii) in addition to the stimulative effect, the GnRH agonist in the presence of gonadotropins also exerts an inhibitory effect, even though the peptide by itself is more effective in the stimulation of steroidogenesis, and the stimulation of gonadotropin on steroidogenesis could be gradually restored by decreasing the concentration of the GnRH agonist in the culture; and (iv) paradoxical effect can also be observed in the presence of cAMP-inducing agents, suggesting that the inhibitory action of the peptide on gonadotropin-induced steroidogenesis is localized at a step distal to the stringent recognition sites.