It has been shown before that LH induces CREB phospho rylation and that e pression of a dominant nega tive CREB variant was enough to block androgen biosynthesis in rat TIC cells. We observed that prein cubation with UTP, completely blocked the hCG induced CREB phosphorylation, which suggests that the purinergic system potently modulates LH acti vated pathways, an action that might have important con sequences in ovarian theca physiology. Is well known that during folliculogenesis LH e erts regulatory actions beginning around the formation of early secondary follicles, which is concurrent with theca layer differentiation. from this stage throughout folliculo genesis up to ovulation, LH is the main regulator of theca layer development, because it controls the steroidogene sis process.

However, during this period, important phenomena such as follicular selection or dominance processes cannot be e plained solely by LH action. para crine and autocrine Inhibitors,Modulators,Libraries follicular molecules seem to be essential for the final outcome. It is possible that P2Y2 activation represents one of the mechanisms by which LH regulates the cohort of follicles that will or will not become dominant. Thus, the process of purinergic regulation demonstrated here might be involved in main taining the proper Inhibitors,Modulators,Libraries balance between the rate of cell divi sion and death in the ovary, and in essential physiological Drug_discovery actions such as steroidogenesis, functioning as a local, fine tuning modulator to complement the systemic con trol e erted by hormones and nervous system afferents.

Hence, purinergic regulation is a potential therapeutic target in ovarian pathologies where proliferation or the steroidogenesis processes are affected. Specifically in regulating the balance between theca proliferation and death, our data suggest that activation of the purinergic system by ATP could have dual effects on theca cell physiology. i. e, depending Inhibitors,Modulators,Libraries on the concen tration, ATP might induce 1 apoptotic cell death through P2 7 receptors and 2 cell proliferation through P2Y2 P2Y6 receptors, as shown here. This is similar to what has been demonstrated in other systems in which the cells seem to co e press multiple purinergic receptor subtypes, leading to activation of multiple sig naling pathways.

For e ample, macrophages e press Inhibitors,Modulators,Libraries a variety of P2 and P2Y purinergic receptors, and their activation modulates diverse physiological process such as apoptosis, activation of cell proliferation pathways, or activation of the inflammatory response machinery. The final physiological outcome of the effect e erted by ATP in a given process will be determined by several factors including, for e ample, the purinergic receptor affinities, source and availability of ATP, ecto ATPase activity, and also cross talk between different G protein coupled receptor types or subunits of receptor channels ].