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Relative Effect of Gonadotropin-Releasing Hormone (GnRH)-I and GnRH-II on Gonadotropin Release

Division of Neuroscience (V.S.D., H.F.U.), Oregon National Primate Research Center, Beaverton, Oregon 97006; and Department of Physiology and Pharmacology (H.F.U.), Oregon Health and Science University, Portland, Oregon 97239

Address all correspondence and requests for reprints to: Henryk F. Urbanski, Division of Neuroscience, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, Oregon 97006. E-mail: urbanski{at}ohsu.edu.

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 µg/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 µg/kg body weight) together with a single injection of GnRH-I or GnRH-II (1 µg/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.

This work was supported by National Institutes of Health Grants RR00163, HD29186, and AG19100 (to H.F.U.) and DK07680 (to V.S.D.).

Abbreviations: FSHRH, FSH-releasing hormone; HBSS, Hanks’ balanced salt solution; H-F, Huynh-Feldt.

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