Dose-Response Studies for Pituitary and Testicular Function in Male Dogs Treated with the GnRH Superagonist, Deslorelin

• Published in: Reproduction in domestic animals 2009-10, Vol.44 (5), p.725-734
• Main Authors: Junaidi, A, Williamson, PE, Martin, GB, Blackberry, MA, Cummins, JM, Trigg, TE
• Format: Article
• Language: English
• Subjects: Animal reproduction; Animals; Biological and medical sciences; Contraceptive Agents, Male - administration & dosage; Dogs; Dogs - physiology; Dose-Response Relationship, Drug; Drug Implants; Fundamental and applied biological sciences. Psychology; Gonadotropin-Releasing Hormone - agonists; Kinetics; Luteinizing Hormone - blood; Male; Males; Mammalian reproduction. General aspects; Pharmacology; Pituitary Gland - drug effects; Pituitary Gland - physiology; Semen - cytology; Semen - drug effects; Sperm Count; Sperm Motility; Testis - anatomy & histology; Testis - drug effects; Testis - physiology; Testosterone - blood; Triptorelin Pamoate - administration & dosage; Triptorelin Pamoate - analogs & derivatives; Vertebrates: reproduction; Veterinary medicine
• ISSN: 0936-6768; 1439-0531
• DOI: 10.1111/j.1439-0531.2008.01060.x

We tested the effect of dose of GnRH superagonist on pituitary and testicular function in a study with four groups of four male dogs. The Controls received blank implants and the other three groups received implants containing 3, 6 or 12 mg deslorelin ( d-Trp⁶-Pro⁹-des-Gly¹⁰-GnRH ethylamide). In all deslorelin-treated groups, there was initially an acute increase in plasma concentrations of LH and testosterone, followed by declines such that both hormones became undetectable after approximately 12 days. There was a dose-response in some of these early aspects of the hormone profiles. With respect to long-term effects of treatment, the 12-mg dose had significantly greater effects than the smaller doses for the duration of minimum testicular volume [366 ± 77, mean ± SEM (3 mg), 472 ± 74 (6 mg), and 634 ± 59 (12 mg) days], absence of ejaculate [416 ± 88 (3 mg), 476 ± 83 (6 mg), and 644 ± 67 (12 mg) days], undetectable plasma concentrations of LH and testosterone [367 ± 64 (3 mg), 419 ± 72 (6 mg), and 607 ± 69 (12 mg) days], the delay until complete recovery of LH and testosterone secretion [394 ± 65 (3 mg), 484 ± 72 (6 mg) and 668 ± 47 (12 mg) days], and the delay until testes had regrown to normal volume [408 ± 77 (3 mg), 514 ± 74 (6 mg), 676 ± 59 (12 mg) days]. The time taken to restore full ejaculates was also longest for the 12-mg dose: 716 ± 67 (12 mg) days vs 440 ± 66 (3 mg) and 538 ± 83 (6 mg) days after implantation. There was no correlation between delay to recovery of normal ejaculate quality and body mass. We conclude that the dose-response relationship with deslorelin implants is not expressed with respect to the degree of suppression of reproduction, but on the maximum duration of suppression and thus to delay until recovery.