Temporal changes in FSH and LH concentrations following the administration of a potent LH-RH inhibitory analogue ( [N-Ac-D-Trp1, 3, D-p-Cl-Phe2, D-Phe6, D-Ala10]-LH-RH) to oophorectomized rhesus monkeys.
A series of studies was performed in order to assess the antigonadotropic potency of an inhibitory analogue of LH-RH (IA-LH-RH) ( [N-Ac-D-Trp1, 3, D-p-Cl-Phe2, D-Phe6, D-Ala10]-LH-RH) in oophorectomized rhesus monkeys. I) Single administration of 1 mg IA-LH-RH im resulted in a prompt and significant decrease of serum levels of FSH and LH which lasted for at least 24 h. A specific rebound of serum LH to higher concentrations than baseline occurred in all animals at +48 or +72 h. II) Exogenous LH-RH at a dose of 150 micrograms was administered iv 2 or 18 h after the injection of 1 mg IA-LH-RH. Blood was drawn at 0, 10, 20, 30, 60, 120 and 180 min post LH-RH. The rise in LH and FSH levels observed in the control animals was not altered when LH-RH was administered 2 h after the antagonist, but it was significantly inhibited and delayed when LH-RH was given 18 h after the LH-RH inhibitory analogue. These results show that antagonistic analogues of LH-RH are potent inhibitors of gonadotropin concentrations in non-human primates. Their potential use in conditions in which inhibition of gonadotropin secretion and/or release is desired is discussed.