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 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 μg 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 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.