IN-VIVO ACTIONS OF A GONADOTROPIN-RELEASING-HORMONE (GNRH) ANTAGONISTON GONADOTROPIN-II AND GROWTH-HORMONE SECRETION IN GOLDFISH, CARASSIUS-AURATUS

In our previous in vitro studies, [Ac-Delta(3)-Pro(1), 4FD-Phe(2), D-T rp(3,6)]-mGnRH (analog E) suppressed both gonadotropin-II (GTH-II) and growth hormone (GH) release stimulated by sGnRH and cGnRH-II. In the present study analog E significantly inhibited the increases in plasma GTH-II levels stimulated by sGnRH in sexually mature female and sexua lly recrudescent goldfish. Treatment of goldfish with cl-methyl-p-tyro sine methyl ester (alpha-MPT) inhibits dopamine synthesis and abolishe s the inhibitory actions of dopamine on GTH-II release, resulting in a potentiation of the GTH-II response to sGnRH. Following alpha-MPT pre treatment, analog E significantly reduced basal plasma GTH-II levels, and suppressed both sGnRH and cGnRH-II actions on GTH-II release. Anal og E also inhibited the increase in plasma GTH-II levels in sexually m ature male goldfish exposed to the female sexual pheromone, 17 alpha,2 0 beta-dihydroxy-4-pregnen-3-one (17 alpha 20 beta-P), demonstrating t hat the increase in plasma GTH-II levels is due to release of endogeno us GnRH. Analog E significantly inhibited the increases in plasma GH l evels stimulated by treatment with sGnRH. Implantation of estradiol pe llets increases basal plasma GH levels and increases the GK responsive ness to sGnRH in sexually recrudescent goldfish; analog E also suppres sed the increase in plasma GH levels stimulated by injection of sGnRH in estradiol-treated fish. Analog E suppressed basal GTH-II and GH lev els in fish that were unhandled prior to injection; however, analog E was not effective in reducing basal plasma GTH-II or GH levels in expe riments in which the fish were blood sampled or subjected to some expe rimental manipulation prior to injection of analog E. Analog E also su ppressed basal levels of GTH-II in alpha-MPT-treated fish, suggesting that stress inhibition of GTH-II release may be mediated by the dopami nergic system. In summary, the results demonstrate that (i) analog E c an suppress the actions of exogenous sGnRH and cGnRH-II on GTH-II and GH release in vivo, (ii) the GnRH system mediates, at least in part, t he plasma GTH-II response in sexually mature male goldfish following e xposure to the female sexual pheromone 17 alpha 20 beta-P, and (iii) e ndogenous GnRH peptides are important in the regulation of basal plasm a levels of GTH-II as well as GH, particularly in low stress condition s. (C) 1994 Academic Press, Inc.