Effects of a GnRH cytotoxin on reproductive function in peripubertal male dogs

• Published in: Theriogenology Vol. 66; no. 4; pp. 766 - 774
• Main Authors: Ball, Barry A., Sabeur, Khalida, Nett, Terry, Liu, Irwin K.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2006
• Subjects: Animals; antifertility effect; antineoplastic agents; castration; Cytotoxin; dogs; Dogs - physiology; GnRH; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - chemistry; Gonadotropin-Releasing Hormone - pharmacology; hormone secretion; luteinizing hormone; Luteinizing Hormone - blood; Luteinizing Hormone - secretion; Male; Male dog; male fertility; Organ Size - drug effects; Protein Synthesis Inhibitors - pharmacology; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - pharmacology; Reproduction - drug effects; Reproduction - physiology; Ribosome Inactivating Proteins, Type 1 - pharmacology; Sexual Maturation - drug effects; Sterilization; testes; Testis; Testis - cytology; Testis - drug effects; testosterone; Testosterone - blood; Time Factors; Testis; Male dog; Cytotoxin; GnRH; Sterilization
• ISSN: 0093-691X; 1879-3231
• DOI: 10.1016/j.theriogenology.2005.11.024

Methods for long-term or permanent disruption of reproductive function via nonsurgical techniques are needed for a variety of species, including companion animals. In a previous study, we demonstrated the ability of a cytotoxin (pokeweed antiviral protein—PAP) conjugated to d-Lys6-GnRH, to disrupt reproductive function in adult male dogs. The objective of the present study was to examine the ability of a d-Lys6-GnRH-PAP conjugate to disrupt reproductive function in peripubertal male dogs. Peripubertal male dogs (n=15; approximately 16–32 weeks old) were treated with d-Lys6-GnRH-PAP as follows: dogs (n=7; Group I) received GnRH-PAP (0.1mg/kg SQ) with a second treatment (0.25mg/kg) 20 weeks later. An additional group (n=3; Group II) of peripubertal dogs was treated with GnRH-PAP (0.25mg/kg) twice (20 weeks apart). Control dogs (n=5) received d-Lys6-GnRH analog (0.0045mg/kg SQ) without PAP. Efficacy was assessed by monitoring testis size, serum concentrations of testosterone and LH, as well as LH release subsequent to a GnRH (5μg/kg) stimulus. Dogs in Group I (n=5) that did not respond to the initial two treatments were given a third GnRH-PAP injection (0.25mg/kg), 12 months after the initial treatment. The initial GnRH-PAP treatment in peripubertal male dogs did not affect testis growth, LH release or serum testosterone concentrations; however, administration of a higher dose of GnRH-PAP after puberty resulted in a marked and rapid decline in testis size, serum testosterone concentrations and LH responsiveness to GnRH stimulation in 9 of 10 dogs. Suppression of reproductive function was maintained in treated dogs for 18–50 weeks; four dogs had suppression of reproductive activity through the end of the study. In conclusion, GnRH-PAP given after puberty markedly suppressed reproductive activity. Due to variability in the response and duration of suppression after treatment with GnRH-PAP, more research is required to determine its efficacy for nonsurgical sterilization of the male dog.