title: Effects of a GnRH cytotoxin on reproductive function in peripubertal male dogs.
abstract: 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-Lys(6)-GnRH, to disrupt reproductive function in adult male dogs. The objective of the present study was to examine the ability of a d-Lys(6)-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-Lys(6)-GnRH-PAP as follows: dogs (n=7; Group I) received GnRH-PAP (0.1 mg/kg SQ) with a second treatment (0.25 mg/kg) 20 weeks later. An additional group (n=3; Group II) of peripubertal dogs was treated with GnRH-PAP (0.25 mg/kg) twice (20 weeks apart). Control dogs (n=5) received d-Lys(6)-GnRH analog (0.0045 mg/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 (5 microg/kg) stimulus. Dogs in Group I (n=5) that did not respond to the initial two treatments were given a third GnRH-PAP injection (0.25 mg/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.
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, United States. baball@ucdavis.edu
authors.forename: Barry A
authors.initials: BA
authors.lastname: Ball
authors.forename: Khalida
authors.initials: K
authors.lastname: Sabeur
authors.forename: Terry
authors.initials: T
authors.lastname: Nett
authors.forename: Irwin K M
authors.initials: IK
authors.lastname: Liu
mesh_terms: D000818:Animals; D004285:Dogs / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology*; D012741:Sexual Maturation / Q000187:drug effects*; D013737:Testis / Q000166:cytology / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D013997:Time Factors
chemical_list: D011500:Protein Synthesis Inhibitors; D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; C024275:pokeweed antiviral protein