Antagonistic activity of analogs of luteinizing hormone-releasing hormone (LH-RH) in vitro.

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.