New GnRH analogs in canine reproduction.
Gonadotropin-releasing hormone (GnRH) analogs, which include agonists and antagonists, have been produced by amino acid substitutions of the native GnRH molecule to create greater potency and longer duration of effectiveness. The aim of this article was to review the pharmacological effects and the existing clinical literature of new GnRH analogs, namely agonists released from long-term formulations and third generation antagonists, in domestic dogs. Long-term administration of agonists functions through desensitization and down-regulation of GnRH pituitary receptors inhibiting gonadotropin production and release after an initial stimulation. Conversely, GnRH antagonists bind to gonadotrope GnRH receptors and compete successfully with endogenous GnRH for occupancy, thereby inhibiting the pituitary-gonadal axis immediately. There is a promising place for both agonists and antagonists in future canine reproduction. They can be used in the control of estrous cycle, hormone-dependent diseases as well as in contraception. Some information on the effectiveness and safety of these new analogs in canine reproduction is already available, yet further work is needed before they could be widely recommended. The increase in gonadotropins and gonadal steroids following administration of agonists might have adverse effects when used on hormone-dependent diseases. This initial "flare" should also be carefully managed in anestrous and prepubertal bitches. At present, the main application of antagonists seems limited to situations where an acute endocrine, inhibitory effect is required, e.g. proestrus or pregnancy termination. Future commercial availability of long-acting, single-dose antagonists could go far towards controlling pet population.
Gobello
Cristina
C
Animal Physiology, Faculty of Veterinary Medicine, National University of La Plata, La Plata, Argentina. cgobello@netverk.com.ar
D000818:Animals; D004285:Dogs / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology
D007987:Gonadotropin-Releasing Hormone