Inhibitory effects of long-term repeated treatments of a sustainable GnRH antagonist, degarelix acetate, on caprine testicular functions

Abstract

We investigated the effects of long-term repeated treatments with a sustainable gonadotropin-releasing hormone (GnRH) antagonist, degarelix acetate, on testicular hormonal secretion, size, ultrasound images, histology and spermatogenesis in goats to assess its efficacy as a chemical castration method. Male Shiba goats (3-6 months of age) were treated subcutaneously with degarelix acetate every 4 weeks for 24 weeks. Plasma testosterone and insulin-like peptide 3 (INSL3) concentrations decreased (P<0.05) within 2 days after the first treatment and remained low until 29 weeks (P<0.05). Scrotal circumference and testicular pixel intensity were lower from 2-6 months and from 1-6 months, respectively, compared to the pretreatment values (P<0.05). The testis and epididymis weights were lower at 24 weeks compared to those in untreated goats (P<0.05). There were no sperm in the seminiferous tubules of testicular tissue sections or in homogenates of the epididymis at 24 weeks. These results suggest that repeated treatment with degarelix acetate is an effective chemical castration method for goats.

Insulin‐like peptide 3 in domestic animals with normal and abnormal reproductive functions, in comparison to rodents and humans

“… 77 , 89 Also, we have suggested that suppression of pulsatile LH release by a long‐acting GnRH antagonist, degarelix acetate, induced immediate reduction of testosterone secretions followed by INSL3 with a few days delay in male goats, indicating a slower decrease of INSL3 secretion in response to reductions of pulsatile LH release than that of testosterone. 78 , 90 Additions of human chorionic gonadotropin (hCG), which has LH actions, to cultured canine testicular interstitial cells for 18 h stimulated INSL3 release in vitro. 91 On the other hand, in men, serum INSL3 levels did not change by an hCG treatment in a daily blood sample for 8 days, whereas testosterone increased for a few days after treatment, 92 suggesting that the INSL3 secretion is not acutely regulated by LH.…”

“…77,89 Also, we have suggested that suppression of pulsatile LH release by a long-acting GnRH antagonist, degarelix acetate, induced immediate reduction of testosterone secretions followed by INSL3 with a few days delay in male goats, indicating a slower decrease of INSL3 secretion in response to reductions of pulsatile LH release than that of testosterone. 78,90 Additions of human chorionic gonadotropin (hCG), which has LH actions, to cultured canine testicular interstitial cells for Abbreviations: EIA, enzyme immunoassay; HRP, horseradish peroxidase; LC-MS/MS, liquid chromatography-tandem mass spectrometry; RIA, radioimmunoassay; TRFIA, time-resolved fluorescence immunoassay.…”

“…The authors have shown by serial blood sampling with 15‐min intervals for 8 h that pulsatile INSL3 secretion into blood circulation was acutely upregulated by LH pulses and that the increase of INSL3 by the LH was much lower than that of testosterone in bulls and male goats (Figure 6). 77,89 Also, we have suggested that suppression of pulsatile LH release by a long‐acting GnRH antagonist, degarelix acetate, induced immediate reduction of testosterone secretions followed by INSL3 with a few days delay in male goats, indicating a slower decrease of INSL3 secretion in response to reductions of pulsatile LH release than that of testosterone 78,90 . Additions of human chorionic gonadotropin (hCG), which has LH actions, to cultured canine testicular interstitial cells for 18 h stimulated INSL3 release in vitro 91 .…”