Relative effect of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on gonadotropin release

Two forms of GnRH (GnRH-I and GnRH-II) are expressed in the hypothalamus of humans and rhesus monkeys, but their relative abilities to stimulate LH and FSH release are unknown. Therefore, young (8-12 yr) and old (21-23 yr) female rhesus monkeys were treated iv with bolus injections of either GnRH-I or GnRH-II (dose range, 0.01-10 mug/kg body weight); serial blood samples were remotely collected through a vascular catheter for up to 2 h after injection. Overall, plasma LH concentrations were similarly elevated after treatment with GnRH-I and GnRH-II, and the responses were slightly greater in the younger animals. Although plasma FSH concentrations were unaffected by a single exposure to GnRH-I or GnRH-II, they showed a similar significant increase after repeated exposures (every 2 h for 24 h). In a subsequent experiment, antide, a GnRH-I receptor antagonist, was administered (100 mug/kg body weight) together with a single injection of GnRH-I or GnRH-II (1 mug/kg body weight). As expected, GnRH-I induced LH release was significantly attenuated by this combined treatment; moreover, GnRH-II-induced LH release was completely blocked. Taken together, these data show that GnRH-II can potently stimulate gonadotropin release in vivo and that this action is likely mediated through the GnRH-I receptor.