Effects of GnRH Antagonists vs Agonists in Domestic Carnivores, a Review

Abstract

Contents Gonadotrophin‐releasing hormone (GnRH) stimulates the pituitary secretion of both luteinizing and follicle‐stimulating hormones, and thus controls the hormonal and reproductive functions of the gonads. GnRH analogs, which include agonists and antagonists, have been produced by amino acid substitutions within the native GnRH molecule resulting in greater potency and a longer duration of effectiveness. While the initial antagonists produced significant side effects, more recent potent, long‐acting, water‐soluble, low histamine‐release third‐generation compounds such as cetrorelix, abarelix, azaline B and acyline have appeared. Differently to GnRH agonists, antagonists competitively block and inhibit GnRH‐induced GnRH receptor gene expression leading to an immediate, dose‐dependent, pituitary suppression without an initial stimulation of the gonadal axis. The aims of this review are to compare the effects of GnRH agonists vs antagonists and to describe the existing literature concerning new antagonists in domestic carnivores. In male dogs, a single subcutaneous dose of acyline safely and reversibly decreased serum gonadotrophins and testosterone concentrations for 9 days and prevented physiological response of gonadal the axis to agonistic challenge for 14 days. The same protocol reversibly impaired spermiogenesis, spermatocytogenesis and semen quality in both cats and dogs. In females, third‐generation GnRH antagonists prevented ovulation and interrupted pregnancy in canids but not in felids. During anestrus, a single acyline injection exhibited limited prevention of the ‘flare‐up’ effect in GnRH agonist‐implanted bitches. Although GnRH antagonists appear to have a promising future in domestic carnivores reproduction, the information is still scarce and further work is needed before they can be widely recommended.

Pharmacological Treatment for Common Prostatic Conditions in Dogs – Benign Prostatic Hyperplasia and Prostatitis: an Update

“…The initial two generations of GnRH antagonists presented weak effectiveness and exhibited side effects such as histamine release leading to anaphylactic reactions. Recently, a new series of potent, acceptably long‐lasting (≤10 days) low‐histamine‐release third‐generation GnRH antagonists were developed – cetrorelix, abarelix, ganirelix, which are marketed and others such as antarelix, teverelix, degarelix, ozarelix, ornirelix, acyline (Gobello ). A detailed review has been presented by Gobello ().…”

“…Recently, a new series of potent, acceptably long‐lasting (≤10 days) low‐histamine‐release third‐generation GnRH antagonists were developed – cetrorelix, abarelix, ganirelix, which are marketed and others such as antarelix, teverelix, degarelix, ozarelix, ornirelix, acyline (Gobello ). A detailed review has been presented by Gobello (). An example of a drug belonging to this group and recently intensively tested in humans for androgen deprivation therapy (ADT) is degarelix.…”

Investigation of the efficacy of the GnRH agonist deslorelin in mitigating intraspecific aggression in captive male Amur leopards (Panthera pardus orientalis)

“…In this report, intraspecific aggression between intact male leopards was mitigated by the placement of deslorelin implants enabling continued social housing of the pair. Deslorelin has been reported to stimulate the HPGA initially resulting in a surge in testosterone for 2 to 3 weeks before chemical castration is achieved (Gobello, ). A similar surge in androgen may account for the initial increased frequency of aggressive behaviors observed in leopard Two in weeks 1–3 post‐implantation.…”

Non-surgical castration methods to control stray dog population, a review.

“…In 2006 an implant containing nafarelin at a dose of 18.5 mg, called Gonazon, was introduced on the European market. This compound is inserted in the umbilical region in dogs, and in the neck in cats (Gobello, 2012). Another formulation of GnRH agonist is marketed as the implant Suprelorin comprising of a GnRH analogue, named deslorelin.…”