Sustained inhibitory actions of a potent antagonist of gonadotropin-releasing hormone in postmenopausal women.
The inhibitory time course and dose-related characteristics of a new potent GnRH antagonist peptide, [N-acetyl-D-pCl-Phe1,2-D-Trp3-D-Lys6-D-Ala10]GnRH, on gonadotropin secretion were studied in nine postmenopausal women. Effective suppression of gonadotropin secretion was correlated with increased circulating concentrations of immunoassayable GnRH antagonist. Inhibition of gonadotropin secretion was achieved by a parenteral dose of 300 micrograms/kg GnRH antagonist. This dose reduced plasma bioactive LH concentrations by 49-59%, immunoactive LH by 41-46%, and immunoactive FSH by 25-40%. Blockade of gonadotropin secretion was sustained for 10-28 h after a single injection of the synthetic decapeptide. This prolonged action was associated with significant plasma protein binding of the GnRH antagonist and mean plasma half-times of disappearance of 1.5 and 21 h for the fast and slow components, respectively. In summary, we have described the biological actions of a potent GnRH antagonist that binds avidly to serum proteins, has a prolonged plasma residence time, and exerts sustained inhibitory effects on bio- and immunoactive LH release in man. The extended duration of action of this compound may reflect in part its significant binding to circulating plasma proteins.
D000368:Aged; D001798:Blood Proteins / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D006062:Gonadotropins / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008593:Menopause; D008875:Middle Aged; D010906:Pituitary Hormone-Releasing Hormones / Q000037:antagonists & inhibitors*; D012882:Skin Tests; D013972:Thyrotropin / Q000097:blood
D001798:Blood Proteins; D006062:Gonadotropins; D010906:Pituitary Hormone-Releasing Hormones; D007987:Gonadotropin-Releasing Hormone; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; C043124:N-Ac-(4-Cl-Phe)(1)-(4-Cl-Phe)(2)-Trp(3)-Lys(6)-AlaNH2(10)-LHRH; D013972:Thyrotropin; D006854:Hydrocortisone