Effect of GnRH conjugated to pokeweed antiviral protein on reproductive function in adult male dogs.
This study evaluated the effect of a GnRH analogue conjugated to the cytotoxin, pokeweed antiviral protein (PAP), on reproductive function in adult, male dogs. Four dogs received 0.0042 mg GnRH-PAP kg(-1) hourly for 36 h, and four other dogs received 0.1 mg GnRH-PAP kg(-1) as one bolus injection daily for three consecutive days. One dog received a single bolus (0.1 mg x kg(-1)). Three adult male dogs received GnRH without the PAP conjugate, as controls. Twenty-five weeks after the initial treatment, all treated dogs received 0.1 mg GnRH-PAP kg(-1) as a single administration, whereas dogs in the control group received 0.0045 mg kg(-1) of the GnRH analogue. Serum concentrations of testosterone and LH were determined by radioimmunoassay, and testis size was measured for 9 months after treatment. Stimulation tests (5 microg GnRH kg(-1)) were used to evaluate LH release (-15, 0, 30, 60, 90, 120 min), which was assessed by measuring area under the curve. Serum testosterone concentrations were significantly lower (P<0.05) after treatment in the bolus and hourly groups than in the control group. Testosterone concentrations fell to less than 50 pg x ml(-1) in three of four dogs in the bolus group and one of four dogs in the hourly group by week 8-9 after treatment. Basal LH was lower (P<0.05) in the bolus and hourly groups than in the control group between weeks 0 and 33 after treatment. Treatment with GnRH-PAP reduced (P<0.05) LH release after GnRH stimulation in the bolus and hourly groups compared with the control group. Testis volume was lower (P<0.05) in all treated versus control dogs. In conclusion, administration of the conjugate GnRH-PAP at a 25 week interval resulted in a major disruption of reproductive parameters in male dogs; this effect was maintained for 11-12 weeks after a second injection of GnRH-PAP.
Sabeur
K
K
Department of Population Health and Reproduction, University of California, Davis, CA 95616, USA.
Ball
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Nett
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Ball
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Liu
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D000818:Animals; D019540:Area Under Curve; D003267:Contraception / Q000662:veterinary*; D004285:Dogs; D004334:Drug Administration Schedule; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007267:Injections; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000494:pharmacology*; D012098:Reproduction / Q000187:drug effects*; D054789:Ribosome Inactivating Proteins, Type 1; D013268:Stimulation, Chemical; D013737:Testis / Q000187:drug effects; D013739:Testosterone / Q000097:blood
D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein