Weil C, Breton B, Sambroni S, Zmora N, Zohar Y
Laboratoire de Physiologie des Poissons, INRA, Rennes, France.
Gen Comp Endocrinol. 1992 Jul;87(1):33-43. doi: 10.1016/0016-6480(92)90147-c.
In vitro potencies of native and modified forms of salmon and mammalian gonadotropin-releasing hormone (GnRH) were studied in relation with their susceptibility to degradation by intact pituitary cells maintained in culture. The kinetics of degradation and the origin of the proteases involved in this process were examined. All the molecules tested (native and modified forms) were equipotent at doses between 10(-6) and 10(-7) M in inducing GtH release by cultured pituitary cells. On the other hand, their effectiveness differed at 10(-9) and 10(-8) M leading to the establishment of the following hierarchy of bioactivity: the native forms, LHRH and sGnRH, were the less potent, the fish analogues (DAla6Pro9Net)sGnRH and (DArg6Pro9Net)sGnRH were the more potent, and mammalian analogues with substitutions at position 6 and/or 10 were intermediate in potency. The native form sGnRH was weakly degraded while no degradation of the modified molecules was observed. The degradation of the native sGnRH occurred after 12 and 24 hr of incubation and the results indicate that the peptidases involved are released from the cells into the incubation medium.
研究了天然和修饰形式的鲑鱼及哺乳动物促性腺激素释放激素（GnRH）的体外效价，并将其与培养的完整垂体细胞对其降解的敏感性相关联。研究了降解动力学以及参与该过程的蛋白酶的来源。所有测试的分子（天然和修饰形式）在10^(-6)至10^(-7) M的剂量下，对培养的垂体细胞诱导促性腺激素（GtH）释放的效价相同。另一方面，它们在10^(-9)和10^(-8) M时的有效性不同，从而建立了以下生物活性等级：天然形式的促性腺激素释放激素（LHRH）和鲑鱼促性腺激素释放激素（sGnRH）效力较低，鱼类类似物（D - Ala6Pro9Net）sGnRH和（D - Arg6Pro9Net）sGnRH效力较高，而在第6位和/或第10位有取代的哺乳动物类似物效力处于中间水平。天然形式的sGnRH降解较弱，而未观察到修饰分子的降解。天然sGnRH的降解在孵育12小时和24小时后发生，结果表明所涉及的肽酶从细胞释放到孵育培养基中。
