Cyclic AMP indirectly mediates the extracellular Ca2+-independent release of LH.

This study was undertaken to determine whether cyclic AMP mediates the extracellular Ca2+-independent component of luteinizing hormone (LH) release. Gonadotropin releasing hormone (GnRH) increased cAMP production in female pituitaries incubated in Ca2+-free medium containing 3-isobutyl-1-methylxanthine (IBMX), but was ineffective in male pituitaries. The increases in female pituitaries were inhibited by flufenamate (flu). GnRH-stimulated LH secretion from male pituitaries was completely inhibited in Ca2+-free medium, whereas only a partial inhibition was obtained from female pituitaries, a response prevented by cycloheximide. Infusions of flu completely inhibited the extracellular Ca2+-independent release of LH, while dibutyryl cAMP (dbcAMP) partially restored this component of LH secretion. The dbcAMP-restored response was dependent upon protein synthesis. These results suggest that (i) the extracellular Ca2+-independent component of LH release is indirectly mediated by cAMP through the stimulation of de novo protein synthesis, and (ii) extracellular Ca2+ is required for the activation of adenylate cyclase in male but not in female gonadotrophs.