In vivo actions of a gonadotropin-releasing hormone (GnRH) antagonist on gonadotropin-II and growth hormone secretion in goldfish, Carassius auratus.

In our previous in vitro studies, [Ac-delta 3-Pro1, 4FD-Phe2, D-Trp3,6]-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 sexually recrudescent goldfish. Treatment of goldfish with alpha-methyl-p-tyrosin methyl ester (alpha-MPT) inhibits dopamine synthesis and abolishes the inhibitory actions of dopamine on GTH-II release, resulting in a potentiation of the GTH-II response to sGnRH. Following alpha-MPT pretreatment, analog E significantly reduced basal plasma GTH-II levels, and suppressed both sGnRH and cGnRH-II actions on GTH-II release. Analog E also inhibited the increase in plasma GTH-II levels in sexually mature male goldfish exposed to the female sexual pheromone, 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (17 alpha 20 beta-P), demonstrating that the increase in plasma GTH-II levels is due to release of endogenous GnRH. Analog E significantly inhibited the increases in plasma GH levels stimulated by treatment with sGnRH. Implantation of estradiol pellets increases basal plasma GH levels and increases the GH responsiveness to sGnRH in sexually recrudescent goldfish; analog E also suppressed the increase in plasma GH levels stimulated by injection of sGnRH in estradiol-treated fish. Analog E suppressed basal GTH-II and GH levels in fish that were unhandled prior to injection; however, analog E was not effective in reducing basal plasma GTH-II or GH levels in experiments in which the fish were blood sampled or subjected to some experimental manipulation prior to injection of analog E. Analog E also suppressed basal levels of GTH-II in alpha-MPT-treated fish, suggesting that stress inhibition of GTH-II release may be mediated by the dopaminergic system. In summary, the results demonstrate that (i) analog E can 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, the plasma GTH-II response in sexually mature male goldfish following exposure to the female sexual pheromone 17 alpha 20 beta-P, and (iii) endogenous GnRH peptides are important in the regulation of basal plasma levels of GTH-II as well as GH, particularly in low stress conditions.