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

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Abstract
Antisera to an LH-RH [luteinizing hormone-releasing hormone, luliberin] analog, des-Gly10-[D-Leu6]-LH-RH-ethylamide (TAP 144), were produced in 10 rabbits. By using these antisera, a specific and sensitive radioimmunoassay [RIH] for TAP 144 was established. Sensitivity of the RIA ranged 5-100 pg per assay tube with these antisera. LH [luteinizing hormone, lutropin], FSH [follitropin], TRH [thyroliberin], LH-RH, and the 1-6 fragment of TAP 144 did not practically cross-react with these antisera. The antisera showed a tendency to cross-react with LH-RH analogs, 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 analogs 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 analogs replaced at position 6 by D-amino acids and those altered at position 10 by alkyl-amines, but they showed fairly high cross-reactivities to analogs which are altered simultaneously at both positions 6 and 10. When TAP 144 was administered i.p. 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 i.v., s.c. and i.m. 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 level from 180 min after TAP 144 administration.