Activity of position-8-substituted analogs of mammalian gonadotropin-releasing hormone (mGnRH) and chicken and lamprey gonadotropin-releasing hormones in goldfish.
Several vertebrate gonadotropin-releasing hormones (GnRH) and analogs were tested for activity in vivo in goldfish. Each peptide was administered intraperitoneally to goldfish, pretreated with pimozide or vehicle for pimozide, and changes in serum levels of gonadotropin were determined. Pimozide potentiates the activity of GnRH in vivo in goldfish by blocking the endogenous gonadotropin release-inhibitory activity of dopamine; relative potencies of GnRH peptides become evident in vivo in goldfish pretreated with pimozide (R. Peter et al. (1985), Gen. Comp. Endocrinol. 58, 231-242). Mammalian GnRH (mGnRH) was used as reference standard. [Try3, Leu5, Glu6, Trp7, Lys8]-GnRH (lamprey GnRH), [Gln8]-GnRH (chicken GnRH-I), and [His5, Trp7, Try8]-GnRH (chicken GnRH-II) caused increases in serum gonadotropin level similar in magnitude to mGnRH. [His5, D-Arg6, Trp7, Tyr8]-GnRH is superactive in the goldfish. [Asn8]-, [Met8]-, [Phe8]-, and [Ser8]-GnRH had activity similar to mGnRH in goldfish; [His8]-, [Ile8]-, and [Leu8]-GnRH had a lower level of activity; [Glu8]-GnRH had no apparent activity. The results indicate that there is no particular requirement for a hydrophobic or hydrophilic amino acid, or for a positively charged amino acid in position 8 of mGnRH for activity in vivo in the goldfish; a negatively charged amino acid in position 8 is detrimental for activity.
D000818:Animals; D002645:Chickens; D003530:Cyprinidae / Q000097:blood*; D004357:Drug Synergism; D006054:Goldfish / Q000097:blood*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006062:Gonadotropins / Q000097:blood*; D007798:Lampreys; D010868:Pimozide / Q000494:pharmacology; D013329:Structure-Activity Relationship
D006062:Gonadotropins; D010868:Pimozide; D007987:Gonadotropin-Releasing Hormone