Inhibition of serum luteinizing hormone and testosterone with an inhibitory analog of luteinizing hormone-releasing hormone in adult male rhesus monkeys

Abstract

The effects of single and repeated administration of a potent LHRH inhibitory analog (antagonist) [( N-acetyl-D-p-chloro-Phe1,2,D-Trp3,D-Arg6,D-Ala10]LHRH) on serum concentrations of LH and testosterone (T) in adult rhesus monkeys were studied. In Exp 1, single sc injections of the LHRH antagonist (400 micrograms and 50 micrograms) or vehicle were administered and the temporal changes in serum LH and T were determined (n = 4 per group). Both LH and T declined markedly in all animals as soon as 30 min after the LHRH antagonist injection, reaching the nadir (80%) approximately 8 h later and remaining significantly lower than baseline levels for up to 24 h. Control animals had no marked variations in either LH or T serum levels. In Exp 2, daily sc injections of different doses of LHRH antagonist (400 micrograms, 50 micrograms, and 10 micrograms) or vehicle were administered for 7 days to four animals in each group. The animals in the control group had no significant changes in LH or T levels, whereas those treated with the lowest dose of LHRH antagonist (10 micrograms) had decreased T levels in the absence of changes in LH. The other two doses of LHRH antagonist (400 micrograms and 50 micrograms) induced, as early as 8 h after the initial injection, dramatic decreases in serum levels of both LH and T and these values remained significantly lower than control for up to 3 and 4 days after discontinuation of drug administration, respectively. We conclude from this study that LHRH inhibitory analogs are potent inhibitors of LH and T in adult rhesus monkeys. They have potential use in clinical trials for male contraception as well as in patients in whom inhibition of gonadotropin and steroid secretion is desired.