title: Effects of long-acting GnRH antagonist, degarelix acetate, on plasma insulin-like peptide 3, testosterone and luteinizing hormone concentrations, and scrotal circumference in male goats.
abstract: We recently reported that plasma insulin-like peptide 3 (INSL3) concentrations increased soon after endogenous and exogenous stimulations of LH in male goats and bulls. However, the effects of LH suppression on INSL3 secretion are unknown in domestic animals. Here, we examined the effects of a long-acting GnRH antagonist (degarelix acetate; 4 mg/kg) on the secretions of plasma INSL3 and testosterone in two phases, an immediate and a long-term phase in male goats (n = 6; aged, 13-16 months). During the immediate phase, blood was taken at 15-minute intervals for 8 hours on Days -5, 0, and 3. The GnRH antagonist was administered after 2-hour sampling of Day 0. Moreover, a daily blood sample was taken from Day 0 to Day 7, followed by twice a week until 9 weeks and finally at week 10. The scrotal circumference was recorded before treatment and continued biweekly until week 10. Concentrations of LH, INSL3, and testosterone in plasma were determined by EIA and the pulsatile nature of secretion analyzed using pulse XP software. The mean concentrations, pulse frequency (per hour), and pulse amplitude (peak-nadir) of plasma LH and testosterone reduced from pretreatment to posttreatment Day 0 and Day 3 (P < 0.05). A decline in mean concentrations, pulse frequency, and pulse amplitude of INSL3 was exhibited on posttreatment Day 3 compared with pretreatment (P < 0.01). During long-term sampling, a decline (P < 0.01) in plasma testosterone and INSL3 concentrations was observed 1 day after treatment and remained lower until 8.5 weeks after treatment, and thereafter returned to pretreatment levels. A reduction in scrotal circumference was recorded 4 weeks after treatment and remained lower until 10 weeks after treatment (P < 0.05). In conclusion, the acute regulation of INSL3 by LH was confirmed by reduction of plasma INSL3 levels within 3 days after GnRH antagonist treatment in male goats. Although the onset of suppression of testosterone was more rapid than that of INSL3, the low levels persisted for 8.5 weeks for both hormones, and subsequently the concentrations returned to pretreatment levels. A significant reduction in testicular size was also observed. The quick, long-lasting, and transient suppression of testosterone and INSL3 after a single injection implies a potential application of this antagonist in reversible long-term chemical castration in male goats.
authors: Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
authors: M A
authors: MA
authors: Hannan
authors: Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan. Electronic address: nkawate@vet.osakafu-u.ac.jp.
authors: N
authors: N
authors: Kawate
authors: Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
authors: Y
authors: Y
authors: Fukami
authors: Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
authors: W W P N
authors: WW
authors: Weerakoon
authors: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors: E E
authors: EE
authors: Büllesbach
authors: Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
authors: T
authors: T
authors: Inaba
authors: Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
authors: H
authors: H
authors: Tamada
mesh_terms: D000818:Animals; D006041:Goats / Q000033:anatomy & histology / Q000097:blood / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D007328:Insulin / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood* / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012611:Scrotum / Q000033:anatomy & histology / Q000187:drug effects*; D013739:Testosterone / Q000097:blood* / Q000378:metabolism
chemical_list: D007328:Insulin; C084797:Leydig insulin-like protein; D009842:Oligopeptides; D011506:Proteins; C431566:acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone
keywords: GnRH antagonist; INSL3; LH; Male goat; Scrotal circumference; Testosterone