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Active immunization with GnRH-tandem-dimer peptide in young male rats reduces serum reproductive hormone concentrations testicular development and spermatogenesis

机译:在年轻的雄性大鼠中用GnRH串联二聚体肽主动免疫可降低血清生殖激素浓度睾丸发育和精子生成

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摘要

GnRH sterilization vaccines have been developed for various practical and clinical reasons. However, conjugation of GnRH peptide to carrier protein has many drawbacks, hampering the further commercialization of GnRH vaccines. In this study, a new nonconjugated GnRH vaccine, D-Lys6-GnRH-tandem-dimer peptide (TDK), emulsified in Specol adjuvant was investigated for its immunocastration efficacy in young male rats. Prepubertal male rats were randomly allocated into three groups (n = 12): control (no treatment), surgically castrated or immunized against 100 μg TDK in Specol adjuvant at 6 weeks of age (with a booster 8 weeks later). Blood samples (for antibody titers and hormone concentrations) were collected at 2-week intervals until rats were killed (18 weeks of age). Compared to intact controls, active immunization against TDK reduced (P < 0.05) serum concentrations of testosterone, inhibin B, LH and FSH, prevented the onset of spermatogenesis at puberty. Furthermore, mRNA expressions of GnRH receptor, LH-β and FSH-β in the pituitary, LH receptor, FSH receptor, inhibin α, βA and βB subunit in the testes were decreased in immunocastrated rats compared to intact controls (P < 0.05). These results demonstrate for the first time that GnRH-tandem-dimer peptide emulsified in Specol is a promising veterinary sterilization medicine.
机译:由于各种实际和临床原因,已经开发了GnRH灭菌疫苗。然而,GnRH肽与载体蛋白的结合具有许多缺点,阻碍了GnRH疫苗的进一步商业化。在这项研究中,研究了一种在Specol佐剂中乳化的新型非结合型GnRH疫苗D-Lys6-GnRH串联二聚体肽(TDK)在年轻雄性大鼠中的免疫铸造功效。青春期前的雄性大鼠随机分为三组(n = 12):对照组(未治疗),在6周龄时通过手术cast割或用Specol佐剂中的100μgTDK免疫(8周后加强免疫)。每隔两周收集一次血液样本(用于抗体滴度和激素浓度),直到杀死大鼠(18周龄)。与完整对照相比,针对TDK的主动免疫降低了(P <0.05)血清睾丸激素,抑制素B,LH和FSH的浓度,从而阻止了青春期精子发生的发生。此外,与完整对照组相比,免疫cast割大鼠的垂体GnRH受体,LH-β和FSH-β的mRNA表达,LH受体,FSH受体,抑制素α,βA和βB亚基均降低(P <0.05)。这些结果首次证明在Specol中乳化的GnRH-串联-二聚体肽是有前途的兽医灭菌药物。

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