Purine modulation of LH action in gonadal cells

A rapid and marked amplification of LH and FSH-stimulated cyclic AMP accumulation and steroid secretion is produced by adenosine in luteal and granulosa cells, respectively, of both the rat and the human ovary. The rat Leydig cell response to LH, however, was unaffected by adenosine. In the luteal cell, adenine nucleotides and adenosine were equipotent with decreasing activity shown by inosine, adenine and hypoxanthine-guanosine, guanine, xanthine and pyrimidines were inactive. Both an extra-cellular and intracellular site appears to be involved in adenosine amplification of LH-the extracellular site accounted for about 20% of the response and may be a catalytic receptor site. The intracellular site was directly related to an increase in luteal cell ATP levels in which adnosine appears to serve as a selective prosubstrate for hormone activated adenylate cyclase. The luteal antigonadotropic action of PGF_2α was blocked by adenosine and these modulators were shown to be competitive antagonists of LH-stimulated cyclic AMP accumulation. Due to the ubiquitous nature of both adenosine and PGF_2α, (conditions have been described in other systems for their rapid release,) it is suggested that they may serve as important local humoral modulators of gonadotropin action for regulation and control of ovarian function.