Dose response inhibition of the circhoral pulsatile secretion of LH and FSH in rhesus monkeys by the administration of a potent inhibitory analogue of LH-RH ( [N-Ac-D-Trp1, 3, D-p-Cl-Phe2, D-Phe6, D-Ala10]-LH-RH).

The pulsatility of luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion was evaluated in chronically ovariectomized rhesus monkeys before and after the administration of [N-Ac-D-Trp1, 3, D-p-Cl-Phe2, D-Phe6, D-Ala10]-LH-RH) (IA-LHRH). Animals were divided into three groups (n = 4, each group) receiving, s.c.: 1) vehicle only (controls); 2) 0.5 mg IA-LH-RH; and 3) 2 mg IA-LH-RH. Twelve hours following drug administration, animals were chair-restrained and blood samples drawn every 10 minutes over a period of 4 hours via indwelling femoral vein catheters. LH and FSH levels were measured by RIA to determine the frequency, amplitude and increment of the pulses. Twelve hours after the administration of 0.5 mg or 2.0 mg of IA-LH-RH, levels of LH were reduced by 30 per cent and 68 per cent (P less than 0.001) and those of FSH by 34 per cent and 53 per cent (P less than 0.001 and P less than 0.002), respectively. Doses of 0.5 mg IA-LH-RH decreased the amplitude (20 per cent; P less than 0.001), increment (17 ng/ml; P less than 0.001) and frequency (2 per 4 h; P less than 0.001) of LH pulses. Administration of 2 mg IA-LH-RH produced a fall of increment (8 ng/ml; P less than 0.001), frequency (1 per 4 h; P less than 0.001) and pulse amplitude (26 per cent; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)