A radioimmunoassay for a highly active luteinizing hormone-releasing hormone analogue and relation between the serum level of the analogue and that of gonadotropin.

Antisera to an LH-RH analogue, des-Gly10-[D-Leu6]-LH-RH-ethylamide (TAP-144) were produced in 10 rabbits. By using these antisera, a specific and sensitive radioimmunoassay for TAP-144 was established. Sensitivity of the radioimmunoassay ranged from 5 to 100 per assay tube with these antisera. Lh, FSH, TRH, LH-RH, and the 1-6 fragment of TAP-144 did not practically cross-react with LH-RH analogues, though the degree of the cross-reactivity differed among individual sera. The average cross-reactivity of the 10 antisera showed low specificities to TAP-144 analogues which are altered at positions 2, 3, 4, 5, and 6, but showed high specificities to those altered at positions 8 and 9. The antisera also showed low cross-reactivities to LH-RH analogues replaced at position 6 by D-amino acids and those altered at position 10 by alkylamines, but they showed fairly high cross-reactivities to analogues which are altered simultaneously at both positions 6 and 10. When TAP-144 was administered intraperitoneally to rats on the diestrous day, serum concentrations of TAP-144 increased dose-dependently but maximal serum concentrations of both LH and FSH were attained in response to higher doses of TAP-144. The peak LH and FSH concentrations appeared 70 to 110 min after the peak TAP-144 concentration had been reached. Similar delays in reaching the peak LH and FSH levels were also observed when TAP-144 was administered intravenously, subcutaneously and intramuscularly. When TAP-144 was administered intravaginally, a low but constant serum level of TAP-144 was maintained from 5 to 300 min after the administration, but serum LH and FSH levels declined to a low level from 180 min after the TAP-144 administration.