Effects of the luteinizing hormone-releasing hormone (LHRH) analog D-Trp6-Pro9-NEt-LHRH on the pituitary-gonadal axis of prepubertal rhesus monkeys.

Abstract

To elucidate whether the luteinizing hormone-releasing hormone (LHRH) analog D-Trp6-Pro9-NEt-LHRH (LHRHa) decreases plasma testosterone levels in male primates solely by inhibiting gonadotropin secretion or, in addition, by inhibiting testicular testosterone biosynthesis, we have investigated the effects of this drug on 6 infant male rhesus monkeys. Three animals received LHRHa (12 micrograms . kg . day s.c., experimental group), and 3 animals received saline injections (control group) during the first 2 mo of life. Mean plasma testosterone was significantly lower in the experimental group compared to the control group (54 +/- 7 ng/dl vs. 501 +/- 52 ng/dl, P less than 0.001). The experimental group also had significantly lower mean follicle-stimulating hormone (FSH; 5.1 +/- 0.2 microgram/ml vs. 9.6 +/- 0.7 microgram/ml, P less than 0.001), and bioactive luteinizing hormone (LH; 2.0 +/- 0.08 microgram/ml vs. 3.5 +/- 0.2 microgram/ml, P less than 0.001). To study whether LHRHa influences testicular function directly, all animals were treated with human chorionic gonadotropin (hCG; 100 mIU . kg . day i.m.) for 28 days beginning at 8 mo of age. During Days 15 through 28 we administered LHRHa 12 micrograms . kg . day s.c. to the experimental animals and saline injections to the control group. Plasma testosterone increased to 5827 +/- 557 ng/dl in the experimental group and 4440 +/- 897 ng/dl in the control group after 14 days of hCG treatment. Plasma testosterone concentrations decreased in both groups of animals from Days 15 to 28 fo the study. All steroid intermediates were similar in both groups of animals on Days 14 and 28.(ABSTRACT TRUNCATED AT 250 WORDS)