Effect of endogenous opioid blockade on the amplitude and frequency of pulsatile luteinizing hormone secretion in normal men

The role of endogenous opiates in the neuroendocrine regulation of episodic LH secretion in normal men was examined in seven adult males before and after the administration of a potent and specific opiate receptor antagonist, naltrexone. The quantitative pattern of pulsatile LH secretion was analyzed in serum derived by continuous exfusion of blood in 20- min samples over an 8-h period. The administration of naltrexone markedly increased the following: 1) total area under the continuous LH secretion curve [22, 725 ± 2, 026 (control) vs. 33, 442 ± 2, 226 ng/ml-min (after naltrexone); P < 0.0006]; 2) mean serum concentration of LH, which increased from 47.3 ± 4.2 to 69.7 ± 5.0 ng/ml; 3) the absolute amplitude of LH peaks, which rose from 62.7 ± 6.2 to 85.2 ± 5.8 ng/ml; and 4) the number of LH secretory peaks observed over the 8-h interval (4.3 ± 0.4 basally and 5.4 ± 0.6 after the drug; P < 0.0003). Naltrexone administration did not significantly alter the most rapid component of LH elimination calculated after each pulse or alter the fractional rise in LH above interpulse baseline. These data suggest that endogenous opioids tonically suppress frequency- and amplitude-dependent neuromodulation of LH production, probably through hypothalamic mechanisms that impinge upon gonadotropin-releasing hormone-secreting peptidergic neurons.