Blockade of neonatal activation of the pituitary-testicular axis with continuous administration of a gonadotropin-releasing hormone agonist in male rhesus monkeys.

Abstract

The objective of this study was to determine the effects of continuous GnRH agonist (Ag) treatment on neonatal activation of the pituitary-testicular axis in male rhesus monkeys. Five infants were treated continuously with Ag(10 micrograms/day; Wy-40972) for 112 days using osmotic minipumps beginning at 10-13 days of age. Two of five age-matched control animals were implanted sc with Silastic implants of comparable size to the minipumps; three did not receive sham implants. Ag treatment caused a fall in serum LH (bioassay) values to undetectable levels (much less than 0.1 micrograms/ml) within 3 weeks, where they remained throughout Ag treatment. Mean serum testosterone (T) levels fell from pretreatment values of 1.52 +/- 0.45 to 0.38 +/- 0.09 (+/- SE) ng/ml after 3 weeks of Ag treatment. The level of T never exceeded 0.60 ng/ml throughout the subsequent course of Ag treatment. In contrast, serum LH and T were elevated to levels that approached adult values during the first 2 postnatal months in control infants with or without sham implants. Both LH and T then gradually declined, and by 4 months of age, T levels were indistinguishable from those in Ag-treated animals. Control infants had an increase in serum LH from 0.56 +/- 0.10 to 2.67 +/- 0.49 micrograms/ml within 60 min of administration of 5 micrograms GnRH/kg BW at 60 days of age. Serum T values rose from 2.35 +/- 1.00 to 9.48 +/- 3.15 ng/ml during the same period. Seven weeks of Ag treatment abolished the LH and T responses to GnRH. Thirty days after the termination of Ag treatment (approximately 150 days of age), Ag-treated and control infants had comparable serum LH and T responses to GnRH, although the responses were reduced relative to the responses in controls at 60 days of age. These results suggest that continuous administration of Ag desensitizes the pituitary of the male infant rhesus monkey to GnRH and blocks neonatal activation of the pituitary-testicular axis.