Synthetic polypeptide antagonists of the hypothalamic luteinizing hormone releasing factor

Two analogs of the hypothalamic luteinizing hormone releasing factor modified at the histidine-2 position were tested for biological activity (secretion of luteinizing hormone) in cultures of dispersed rat anterior pituitary cells. The analog in which glycine was substituted for histidine at position 2, [Gly(2)]LRF, behaves as a partial agonist releasing less than 50 percent of the luteinizing hormone secreted at maximum concentrations of the releasing factor, while the analog in which histidine at position 2 is deleted has no significant agonist activity at any of the doses tested. When added to the cultured cells at molar ratios 10(3) to 10(4) times that of the luteinizing hormone releasing factor, both analogs decrease the amount of luteinizing hormone secreted in response to the releasing factor.