Synthetic Polypeptide Antagonists of the Hypothalamic Luteinizing Hormone Releasing Factor

Abstract

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, [Gly²]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 10³ to 10⁴ times that of the luteinizing hormone releasing factor, both analogs decrease the amount of luteinizing hormone secreted in response to the releasing factor.