Millar R P, Milton R C, Follett B K, King J A
Endocrinology. 1986 Jul;119(1):224-31. doi: 10.1210/endo-119-1-224.
Receptor binding and gonadotropin-releasing activity was compared for mammalian GnRH, [Gln8]GnRH (chicken I GnRH), [His5, Trp7, Tyr8]GnRH (chicken II GnRH), [Trp7, Leu8]GnRH (salmon GnRH), and [D-Arg6] chicken II GnRH. The mean ED50 values for mammalian GnRH, chicken I GnRH, chicken II GnRH, and salmon GnRH in stimulating LH release from dispersed chicken pituitary cells were 0.27 nM, 0.28 nM, 0.055 nM, and 0.11 nM, respectively. The relative potencies of the peptides compared in the same assay were 0.93, 1.0, 5.6, and 2.5. The ED50 values for chicken I GnRH, chicken II GnRH, and salmon GnRH in stimulating FSH release were 0.37 nM, 0.034 nM, and 0.18 nM, and the relative potencies were 1.0, 13.5, and 1.8. Chicken II GnRH was, therefore, more potent than chicken I GnRH and mammalian GnRH in releasing LH and appeared to have an even greater relative FSH-releasing activity than chicken I GnRH or mammalian GnRH. Introduction of D-Arg6 into chicken II GnRH enhanced the activity of this analog 4- and 2-fold relative to chicken II GnRH in LH- and FSH-releasing activity, respectively. The ED50 values of mammalian GnRH, chicken I GnRH, chicken II GnRH, and salmon GnRH in releasing LH from cultured sheep pituitary cells were 2.9 nM, 96 nM, 22 nM, and 104 nM, respectively. The relative potencies were 1.0, 0.016, 0.084, and 0.047. Introduction of D-Arg6 into chicken II GnRH enhanced activity 9-fold. In a rat pituitary receptor binding assay the ED50 values of mammalian GnRH, chicken I GnRH, chicken II GnRH, and salmon GnRH were 2.9 nM, 1480 nM, 19 nM, and 258 nM, respectively. [D-Arg6]Chicken II GnRH was 46 times more active than the natural chicken II GnRH peptide. The results show: 1) chicken II GnRH is more potent than chicken I GnRH, which is equipotent with mammalian GnRH in releasing LH from chicken pituitary cells. Chicken II GnRH is even more potent at releasing FSH. 2) Salmon GnRH is also more potent than chicken I GnRH and mammalian GnRH in stimulating gonadotropin release from chicken pituitary cells. It appears, therefore, that Trp in the 7 position contributes to the enhanced activity of salmon and chicken II GnRH. 3) The low activity of chicken I GnRH, chicken II GnRH, and salmon GnRH in the sheep pituitary cell bioassay and rat pituitary receptor binding assay confirms that Arg8 in mammalian GnRH is important for activity.(ABSTRACT TRUNCATED AT 400 WORDS)
对哺乳动物促性腺激素释放激素（GnRH）、[谷氨酰胺8]GnRH（鸡I型GnRH）、[组氨酸5、色氨酸7、酪氨酸8]GnRH（鸡II型GnRH）、[色氨酸7、亮氨酸8]GnRH（鲑鱼GnRH）以及[D-精氨酸6]鸡II型GnRH的受体结合及促性腺激素释放活性进行了比较。哺乳动物GnRH、鸡I型GnRH、鸡II型GnRH和鲑鱼GnRH刺激分散的鸡垂体细胞释放促黄体生成素（LH）的平均半数有效剂量（ED50）值分别为0.27 nM、0.28 nM、0.055 nM和0.11 nM。在同一试验中比较的这些肽的相对效价分别为0.93、1.0、5.6和2.5。鸡I型GnRH、鸡II型GnRH和鲑鱼GnRH刺激促卵泡生成素（FSH）释放的ED50值分别为0.37 nM、0.034 nM和0.18 nM，相对效价分别为1.0、13.5和1.8。因此，鸡II型GnRH在释放LH方面比鸡I型GnRH和哺乳动物GnRH更有效，并且在释放FSH方面似乎比鸡I型GnRH或哺乳动物GnRH具有更大的相对活性。将D-精氨酸6引入鸡II型GnRH中，相对于鸡II型GnRH，该类似物在释放LH和FSH活性方面分别增强了4倍和2倍。哺乳动物GnRH、鸡I型GnRH、鸡II型GnRH和鲑鱼GnRH从培养的绵羊垂体细胞释放LH的ED50值分别为2.9 nM、96 nM、22 nM和104 nM。相对效价分别为1.0、0.016、0.084和0.047。将D-精氨酸6引入鸡II型GnRH中使活性增强了9倍。在大鼠垂体受体结合试验中，哺乳动物GnRH、鸡I型GnRH、鸡II型GnRH和鲑鱼GnRH的ED50值分别为2.9 nM、1480 nM、19 nM和258 nM。[D-精氨酸6]鸡II型GnRH的活性比天然鸡II型GnRH肽高46倍。结果表明：1）鸡II型GnRH比鸡I型GnRH更有效，鸡I型GnRH与哺乳动物GnRH在从鸡垂体细胞释放LH方面效力相当。鸡II型GnRH在释放FSH方面甚至更有效。2）鲑鱼GnRH在刺激鸡垂体细胞释放促性腺激素方面也比鸡I型GnRH和哺乳动物GnRH更有效。因此，7位的色氨酸似乎有助于鲑鱼和鸡II型GnRH活性的增强。3）鸡I型GnRH、鸡II型GnRH和鲑鱼GnRH在绵羊垂体细胞生物测定和大鼠垂体受体结合试验中的低活性证实了哺乳动物GnRH中的精氨酸8对活性很重要。（摘要截短于400字）
