GONADOTROPIN-RELEASING ACTIVITIES OF THE 3 NATIVE FORMS OF GONADOTROPIN-RELEASING-HORMONE PRESENT IN THE BRAIN OF GILTHEAD SEABREAM, SPARUS-AURATA

Three forms of gonadotropin-releasing hormone (GnRH) have been recentl y identified in the brain of gilthead seabream (Sparus aurata): salmon GnRH (sGnRH), chicken GnRH-II (cGnRH-II), and a novel form, Ser(8)-ma mmalian GnRH, named seabream GnRH (sbGnRH). sbGnRH is the most abundan t form in the pituitaries of sexually mature seabream during the spawn ing season. The present study investigated the gonadotropin-releasing activities of the three native forms of GnRH found in seabream brains, as well as of two structural analogs of sbGnRH. All native forms of G nRH stimulated gonadotropin-II (GtH-II) secretion in preovulatory fema le seabream. cGnRH-II was found to be 7 to 8 times more potent than sb GnRH and 2 times more potent than sGnRH in inducing GtH-II release. sG nRH was found to be 3.5 to 5 times more potent than sbGnRH in inducing GtH-II secretion. These data demonstrate that cGnRH-II, which is not present in pituitaries of sexually mature seabream, is the most potent GtH-II releaser, whereas sbGnRH, 500 times more abundant than sGnRH i n the pituitary of maturing fish, is the least potent. The lower poten cy of sbGnRH may suggest faster enzymatic breakdown, more rapid cleara nce from the circulation, or a lower binding affinity to the pituitary GnRH receptor. The lower bioactivity of sbGnRH may be compensated for by its high levels in the pituitary. The two analogs of sbGnRH, [D-Na l(2)(6),Pro(9)-NEt]-sbGnRH and [D-Arg(6),Pro(9)-NEt]-sbGnRH, were equi potent to each other and 5 times more potent than sbGnRH in inducing G tH-II release in preovulatory seabream. However, they were 5 to 6 time s less active than the analog of mammalian GnRH, [D-Ala(6),Pro(9)-NEt] -mGnRH. Strategies for designing superactive analogs of sbGnRH are dis cussed. (C) 1995 Academic Press, Inc.