In vitro bioactivities of various forms of GnRH in relation to their susceptibility to degradation at the pituitary level in the rainbow trout, oncorhynchus mykiss

In vitro potencies of native and modified forms of salmon and mammalian gonadotropinreleasing hormone (GnRH) were studied in relation with their susceptibility to degradation by intact pituitary cells maintained in culture. The kinetics of degradation and the origin of the proteases involved in this process were examined. All the molecules tested (native and modified forms) were equipotent at doses between 10^-6 and 10^-7 M in inducing GtH release by cultured pituitary cells. On the other hand, their effectiveness differed at 10^-9 and 10^-8 M leading to the establishment of the following hierarchy of bioactivity: the native forms, LHRH and sGnRH, were the less potent, the fish analogues (DAla⁶Pro⁹Net)sGnRH and (DArg⁶Pro⁹Net)sGnRH were the more potent, and mammalian analogues with substitutions at position 6 and/or 10 were intermediate in potency. The native form sGnRH was weakly degraded while no degradation of the modified molecules was observed. The degradation of the native sGnRH occurred after 12 and 24 hr of incubation and the results indicate that the peptidases involved are released from the cells into the incubation medium.