A comparative study of the mechanism of action of luteinizing hormone and a gonadotropin releasing hormone analog on the ovary

The mechanism of action of a gonadotropin releasing hormone (GnRH) agonistic analog ([D-Ala⁶]GnRH) on the rat ovary has been studied in comparison to similar effects of luteinizing hormone (LH). Stimulation of meiosis resumption in vitro in follicle-enclosed oocytes by both LH and [D-Ala⁶]GnRH, was blocked by elevated levels of cAMP as demonstrated when either dibutyryl cAMP or the phosphodiesterase inhibitor methylisobutylxanthine was present in the culture medium. In vivo, the prostaglandin synthase inhibitor indomethacin, which blocks LH-induced ovulation, also inhibited ovulation induced by the GnRH analog in hypophysectomized rats. On the other hand, the potent GnRH-antagonist [D-pGlu¹, pClPhe², D-Trp^3,6]GnRH which blocked the stimulatory effect of the agonist on oocyte maturation and ovulation had no effect on LH action. It is concluded that while a GnRH-like peptide does not seem to mediate LH action on the ovarian follicles, both LH and GnRH agonist share some common mechanistic pathways at a post-receptor locus.