Purines, prostaglandins and peptides--nature and cellular mechanisms of action of local assist and assassin agents in the ovary.
The evidence for a paracrine, progonadotropic role of adenosine in ovarian cells is summarized along with a capsule review of the origin and mechanisms of release and action of adenosine in other tissues. Briefly, adenosine markedly amplified rat and human luteal cell cyclic AMP and progesterone accumulation in the presence, but not the absence, of LH. The site of action of adenosine was found to be intracellular, linked to its phosphorylation, which resulted in increased levels of ATP. In rat luteal cells, adenosine blocked the acute antigonadotropic (luteolytic) action of PGF2 alpha. In the follicle, adenosine release from granulosal cells appeared to be stimulated by FSH. Adenosine and a nonmetabolized adenosine analog, augmented FSH-dependent inhibition of oocyte maturation in the presence or absence of an adenosine transport inhibitor. Inhibition of oocyte maturation by adenosine thus appears to be mediated by extracellular purinergic receptors. Paracrine, antigonadotropic agents also appear to regulate ovarian function. For example, GnRH elicits antigonadotropic activity in rat granulosal and luteal cells. We describe a novel, GnRH-like, ovarian hormone (GLOH) which may be the physiological ligand whose action GnRH mimics in rat ovarian cells. This protein was shown to be distinctly different from GnRH and a variety of other cyclic and noncyclic peptides. PGF2 alpha is a well known leutolytic agent and a summary of the antigonadotropic mechanism of PGF2 alpha action in rat luteal cells is presented. In these cells, the action of GnRH (or possibly the GnRH-like protein) and PGF2 alpha are mediated by separate membrane receptors but they appeared to share the same intracellular second messenger. Evidence for a role of products of phosphoinositol as a mediator of these antigonadotropic agents is summarized. We suggest that the ultimate mediator of antigonadotropic agents is Ca2+ which is released in the luteal cell in response to the intracellular mediator of antigonadotropic agents. For example, pharmacological agents which increase intracellular levels of Ca2+, mimicked the antigonadotropic action of GnRH and PGF2 alpha in rat luteal cells. Also, Ca2+ directly inhibited LH-sensitive adenylate cyclase activity in isolated luteal membranes, a paradigm in which GnRH and PGF2 alpha were inactive. The mechanism of Ca2+ action appeared to be linked to interference with GTP activation of adenylate cyclase. However, removal of extracellular Ca2+ did not abrogate the action of either GnRH or PGF2 alpha.(ABSTRACT TRUNCATED AT 400 WORDS)
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000502:physiology; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D003338:Corpus Luteum / Q000201:enzymology; D000242:Cyclic AMP / Q000502:physiology; D015237:Dinoprost; D005260:Female; D006801:Humans; D010053:Ovary / Q000187:drug effects*; D010906:Pituitary Hormone-Releasing Hormones / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology*; D051381:Rats
D000067956:Adenylyl Cyclase Inhibitors; D010906:Pituitary Hormone-Releasing Hormones; D011460:Prostaglandins F; D000255:Adenosine Triphosphate; D015237:Dinoprost; D000242:Cyclic AMP; D000241:Adenosine; D002118:Calcium