Griffiths E C, Hopkinson C R
Horm Res. 1979;10(5):233-42. doi: 10.1159/000179005.
Hyperactive analogues of luteinizing hormone-releasing hormone (LH-RH) are beleived to derive their properties from either increased binding affinity to anterior pituitary receptor sites or through decreased susceptibility to enzymic degradation. To investigate the latter suggestion and to examine the possible sites of hypothalamic peptidases inactivating LH-RH, D-Ser(TBU)6-EA10-LH-RH and D-Leu6-EA10-LH-RH, which are known to have considerably greater activity than LH-RH, were incubated with a hypothalamic supernatant fraction containing active peptidases degrading LH-RH, and their gonadotrophin-releasing ability after incubation with the enzymes was tested in normal, adult male rats; LH-RH was also tested in the same way. From a comparison of the relative losses of biological activity, both the LH-RH analogues treated proved to be more resistant to the hypothalamic peptidases than LH-RH itself; the D-Leu6-EA10-LH-RH retained its gonadotrophin-releasing activity longer than the D-Ser(TUB)6-EA10-LH-RH. These findings indicate that increased activity of the analogues may, in part be due to increased resistance to enzymic inactivation and suggest initial sites of cleavage at the Gly-leu and Pro-Gly NH2 bonds in the LH-RH decapeptide by the hypothalamic enzymes. Studies on the action of peptidases on LH-RH and its analogues may yield useful information in the design of peptidase with increased biological activity.
促黄体生成激素释放激素（LH - RH）的活性类似物被认为是因其与垂体前叶受体位点的结合亲和力增加，或对酶促降解的敏感性降低而具有相应特性。为了研究后一种说法，并检查下丘脑肽酶使LH - RH失活的可能位点，将已知活性比LH - RH高得多的D - Ser（TBU）6 - EA10 - LH - RH和D - Leu6 - EA10 - LH - RH与含有能降解LH - RH的活性肽酶的下丘脑上清液部分一起孵育，并在正常成年雄性大鼠中测试它们与这些酶孵育后的促性腺激素释放能力；LH - RH也以同样的方式进行测试。通过比较生物活性的相对损失，结果表明两种经处理的LH - RH类似物比LH - RH本身对下丘脑肽酶更具抗性；D - Leu6 - EA10 - LH - RH比D - Ser（TUB）6 - EA10 - LH - RH保留其促性腺激素释放活性的时间更长。这些发现表明，类似物活性的增加可能部分归因于对酶促失活的抗性增强，并提示下丘脑酶对LH - RH十肽中Gly - leu和Pro - Gly NH2键的初始切割位点。对肽酶对LH - RH及其类似物作用的研究可能会为设计具有更高生物活性的肽酶提供有用信息。
