title: Differential actions of a mammalian gonadotropin-releasing hormone antagonist on gonadotropin-II and growth hormone release in goldfish, Carassius auratus.
abstract: In goldfish 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)Nal1, 4Cl-D-Phe2, D(3)-Pal3,6, Arg5, D-Ala10]-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 microM 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 D1 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-delta 3-Pro1, 4FD-Phe2, D-Trp3,6)-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 125I-(D-Arg6, Pro9 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.
authors.affiliation: Department of Zoology, University of Alberta, Edmonton, Canada.
authors.forename: C K
authors.initials: CK
authors.lastname: Murthy
authors.forename: R J
authors.initials: RJ
authors.lastname: Turner
authors.forename: A O
authors.initials: AO
authors.lastname: Wong
authors.forename: P D
authors.initials: PD
authors.lastname: Rao
authors.forename: J E
authors.initials: JE
authors.lastname: Rivier
authors.forename: R E
authors.initials: RE
authors.lastname: Peter
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D005260:Female; D006054:Goldfish; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011966:Receptors, LHRH / Q000378:metabolism
chemical_list: D006065:Gonadotropins, Pituitary; C089373:LHRH, Ac-Nal(1)-Cpa(2)-Pal(3,6)-Arg(5)-Ala(10)-; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013006:Growth Hormone; C047717:LHRH, His(5)-Trp(7)-Tyr(8)-