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Testosterone with an Inhibitory Analog of Luteinizing Hormone-Releasing Hormone in Adult Male Rhesus Monkeys^*

LUIS A. BURGOS-BRICEÑ, ANDREW V. SCHALLY, ANDRZEJ BARTKE and RICARDO H. ASCH

Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio San Antonio, Texas 78284
Veterans Administration Medical Center, and School of Medicine Tulane University, Department of Medicine, New Orleans, Louisiana 70112

Address correspondence and requests for reprints to: Dr. Ricardo Asch, Department of Obstetrics and Gynecology, the University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284.

The effects of single and repeated administration of a potent LHRH inhibitory analog (antagonist) ([Nacetyl-D--chloro-Phe^1,2,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 fig and 50 fig) 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 µg, 50 µg, and 10 µg) 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 µg) had decreased T levels in the absence of changes in LH. The other two doses of LHRH antagonist (400 µg and 50 µg) 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.

^* This work was supported in part by grants from the Ford Foundation (820-1073), The Program for Applied Research on Fertility Regulation (PARFR), Northwestern University, and Subagreement PARFR (DPE-0546-A-00-1003-00), the NIH Grant SP30HD-10202 (RIA and Bioassay Cores), and the Moody Foundation.

Postdoctoral Fellow.

Received February 22, 1984.