Relative potency of the forms of GnRH and their analogs on LH release in sea bass

The in vivo and in vitro potency of native and modified forms of gonadotropin releasing hormone (GnRH) to release luteotropic hormone (LH) was studied in sea bass Dicentrarchus labrax in particular the hypothalamic fish-specific sea bream GnRH form (sbGnRH) and the general mesoencephalic form chicken GnRH-II (cGnRH-II). The potencies of the natives and their analogs (GnRHas) were referred to that of [D-Ala(6), Pro(9)Net]-mGnRHa (LHRHa) at equivalent doses. Analogs of the native peptides [D-Arg(6), Pro(9)Net]-cGnRH-II [D-Ala(6), Pro(9)Net]-cGnRH-II, [D-Trp(6), Pro(9)Net]-sbGnRH and [D-Ala(6), Pro(9)Net]-sbGnRH were effective in inducing, in vivo LH release (at 151mugkg (1)bodymass), exhibiting longer lasting activity than their corresponding native forms. Injection of sbGnRH and cGnRH-II provoked a small but significant peak of circulating LH at 1.5 h after treatment (a.t.) decreasing down to basal levels at 4h a.t. [D-Arg(6), Pro(9)Net]-cGnRH-II. [D-Ala(6), Pro(9)Net]-cGnRH-II and [D-Ala(6), Pro(9)Net]-mGnRHa evoked a higher and a more sustained elevation of LH, peaking at 12h a.t. and returning, to basal levels between 48 and 72 h a.t. [D-Trp(6), Pro(9)Net]-sbGnRH and [D-Ala(6), Pro(9)Net]-sbGnRH also induced a significant surge of LH in plasma at 4 h a.t. turning to the basal levels at 24h a.t. These rises, however, were of less amplitude and duration than the observed after treatment with cGnRH-II analogs and [D-Ala(6), Pro(9)Net]-cGnRHa. The in vitro stimulation of dispersed Pituitary cells with the different native and modified forms of GnRH resulted in a dose-dependent increase in the qualitity of LH released at 24h a.t.[D-Arg(6), Pro(9)Net]-cGnRH-II and [D-Ala(6), Pro(9)Net]-cGnRH-II induced the highest response of LH hi ritro release followed by salmon GnRH (sGnRH). [D-A ja6, Pro9Nct]mGnRHa and [D-Trp(6), Pro(9)Net]-sbGnRH. The lowest activity was exhibited by sbGnRH. Collectively, the in vitro biological activity (compared by their EC50) can be ordered as follows: [D-Arg(6), Pro(9)Net]-cGnRH-II > [D-Ala(6), Pro(9)Net]-cGnRH-II > sGnRH > [D-Ala(6), 6 Pro(9)Net]-mGnRHa > [D-Trp(6) Pro(9)Net]-sbGnRH > [D-Ala(6), Pro(9)Net]-sbGnRH > cGnRH-II > sbGnRH. (C) 2003 The Fisheries Society of the British Isles.