In goldifish the two native forms of gonadotropin-releasing hormone (GnRH), salmon
GnRH (sGnRH) and chicken GnRH-II (cGnRH-II), stimulate both gonadotropin-II (GTH-II)
and growth hormone (GH) release. Modifications of GnRH structure at positions 1, 2,
3, and 6 often result in an antagonist in goldfish, an observation well documented
in mammalian studies. In a preliminary study in goldfish, a mammalian GnRH antagonist,
[Ac-D(2)Nal<sup>1</sup>, 4Cl-D-Phe<sup>2</sup>, D(3)-Pal<sup>3,6</sup>, Arg<sup>5</sup>,
D-Ala<sup>10</sup>]-mGnRH (analog L) weakly stimulated GTH-II release, and strongly
inhibited GH release. The objectives of the present study were to study the dose-related
actions of analog L on GTH-II and GH release in the goldfish, the specificity of inhibition
of native GnRH actions, and to test whether analog L can act directly on goldfish
pituitary cells. In a goldfish pituitary fragments perifusion system, analog L at
different concentrations, given as 2-min pulses or as 30-min prolonged treatments,
stimulated GTH-II and inhibited GH release in a dose-dependent manner. Analog L at
2 µ M concentration (45 min) significantly suppressed sGnRH- and cGnRH-II-stimulated
GTH-II as well as GH release. Analog L specifically inhibited GnRH-stimulated GH release,
without having any significant effects on the GH release induced by either SKF38393,
a dopamine Dl receptor agonist, or thyrotropin-releasing hormone. The GTH-II stimulatory
and GH-inhibitory actions of analog L were significantly suppressed by a ‘true’ GnRH
antagonist (Ac-Δ<sup>3</sup>-Pro<sup>1</sup>, 4FD-Phe<sup>2</sup>, D-Trp<sup>3,6</sup>)-mGnRH.
Further, analog L stimulated GTH-II release and suppressed GH release from the enzymatically
dispersed goldfish pituitary cells, indicating the direct actions of analog L at the
pituitary cell level. Analog L also displaced <sup>125</sup>I-(D-Arg<sup>6</sup>,
Pro<sup>9</sup> NHEt)-sGnRH bound to crude goldfish pituitary membrane preparations
in a dose-related manner. In conclusion, contrary to its action as a potent GnRH antagonist
in mammals, analog L has GTH-II stimulatory action in goldfish. Analog L by acting
via GnRH receptors at the pituitary cell level differentially acts on GTH-II and GH
release, suggesting functional differences in the properties of the GnRH receptors
on GTH and GH cells. Analog L also specifically inhibits sGnRH and cGnRH-II actions
on GTH-II and GH release.