Effects of Chronic Treatment with a Potent Luteinizing Hormone Releasing Hormone Agonist on Serum Luteinizing Hormone and Steroid Levels in the Male Rhesus Monkey1

Abstract

The effects of chronic administration of [D-Ser(TBU)6, des-Gly-NH210]LHRH ethylamide (Buserelin, Hoe 766) on plasma LH [luteinizing hormone], pregnenolone, 17-hydroxyprogesterone, testosterone and dihydrotestosterone levels were studied in a nonhuman primate species, the rhesus monkey. After 1 wk of daily administration of 25 .mu.g of Hoe 766, the LH response measured after 3 h and 7 h is markedly inhibited when compared to the previous week''s response and a slight decrease of basal LH levels is observed. A small rise of plasma LH is, however, always seen 3 h after administration of the peptide during the whole treatment period. Serum testosterone levels display a rapid stimulation from 7-35 ng/ml 3 h after the 1st administration of Buserelin and increase progressively up to at least 12 h (44 ng/ml). Plasma concentrations of 17-hydroxyprogesterone increase more slowly from 2.0 to 3.4 ng/ml during the first 3 h and reach 9.5 ng/ml 9 h later. By contrast, there are no or minimal changes of serum pregnenolone and dihydrotestosterone levels following the 1st injection of Hoe 766 and during the course of the study. While the acute testosterone response to Buserelin measured at 3 h is not affected in up to 7 wk of treatment with the peptide, the duration of testosterone and 17-hydroxyprogesterone response measured at later time intervals (7 h, 12 h) is decreased to 20%-50% of control. The testicular steroidogenic pathway in rhesus monkeys retains its ability to respond to LH stimulation during treatment with the LHRH agonist while the basal testosterone levels are reduced. The close correlation observed between reduced serum LH and testosterone concentrations suggest that pituitary desensitization is the main factor responsible for the partial inhibition of basal testosterone concentration in rhesus monkeys.