Coy D H, Labrie F, Savary M, Coy E J, Schally A V
Mol Cell Endocrinol. 1976 Aug-Sep;5(3-4):201-8. doi: 10.1016/0303-7207(76)90083-6.
The ability of eighteen analogs of LH-RH to inhibit LH-RH-induced LH release was tested in primary cultures of rat anterior pituitary cells. [Des-His2]LH-RH, [Des-His2, D-Leu6]LH-RH and [Des-His2, D-Phe6]LH-RH inhibited 50% of LH-RH-induced LH release at molar ratios (MR50S) of 3000, 500 and 60, respectively, while [D-Phe2]LH-RH, [D-Phe2, D-Leu6]LH-RH and [D-Phe2, D-Phe6]LH-RH had similar effects at MR50S of 1000, 150 and 25, respectively. This indicates that substitution of D-phenylalanine for histidine at position 2 of LH-RH leads to compounds approximately 3-fold more potent than the corresponding [Des-His2]-analogs. [D-Phe2, D-Phe6]LH-RH, the most potent antagonist tested has however a slight agonistic activity (0.003% that of LH-RH itself). [D-Phe2, D-Phe6, Phe7]LH-RH, [D-Phe2, Phe3, D-Phe6]-LH-RH and [D-Phe2, Phe5, D-Phe6]LH-RH inhibit 50% of LH-RH action at MR50S of 400, 100 and 75, respectively. All of the analogs mentioned in the last group have LH-releasing activities below 1/100,000 that of LH-RH itself.
在大鼠垂体前叶细胞原代培养中测试了18种促黄体激素释放激素（LH-RH）类似物抑制LH-RH诱导的促黄体生成素（LH）释放的能力。[去组氨酸2]LH-RH、[去组氨酸2，D-亮氨酸6]LH-RH和[去组氨酸2，D-苯丙氨酸6]LH-RH分别在摩尔比（MR50）为3000、500和60时抑制50%的LH-RH诱导的LH释放，而[D-苯丙氨酸2]LH-RH、[D-苯丙氨酸2，D-亮氨酸6]LH-RH和[D-苯丙氨酸2，D-苯丙氨酸6]LH-RH分别在MR50为1000、150和25时具有类似作用。这表明在LH-RH的第2位用D-苯丙氨酸取代组氨酸会产生比相应的[去组氨酸2]类似物效力约高3倍的化合物。然而，测试的最有效拮抗剂[D-苯丙氨酸2，D-苯丙氨酸6]LH-RH具有轻微的激动活性（为LH-RH自身活性的0.003%）。[D-苯丙氨酸2，D-苯丙氨酸6，苯丙氨酸7]LH-RH、[D-苯丙氨酸2，苯丙氨酸3，D-苯丙氨酸6]LH-RH和[D-苯丙氨酸2，苯丙氨酸5，D-苯丙氨酸6]LH-RH分别在MR50为400、100和75时抑制50%的LH-RH作用。最后一组中提到的所有类似物的LH释放活性均低于LH-RH自身活性的1/100,000。
