Endogenous opioids modulate the inhibitory effects of androgen on the hypothalamic-pituitary axis of normal women

This study was designed to investigate the effect of dihydrotestosterone (DHT) on LH secretion in normal women and the role of endogenous opioids in modulating this effect. Pulsatile LH release and maximum LH responsiveness to exogenous GnRH were determined on 3 consecutive days: basally (day 1), during DHT infusion (day 2), and during DHT plus naloxone (Nal) infusion (day 3). Steady state plasma DHT levels of 6.5 +/- 1.1 (+/- SEM) ng/mL (22.5 +/- 3.8 nmol/L) were achieved by infusion. DHT infusion significantly decreased the maximum LH response to GnRH from 35.5 +/- 8.2 to 11.6 +/- 2.8 IU/L (P less than 0.05). This inhibitory effect was not altered by Nal. In addition, DHT significantly decreased LH pulse frequency (basal, 4.3 +/- 0.3; DHT, 2.8 +/- 0.3 pulses/6 h; P less than 0.05), but not the amplitude of the LH pulses. However, after the addition of Nal to DHT, the pulse frequency increased significantly from 2.8 +/- 0.3 to 4.7 +/- 0.3 pulses/6 h (P less than 0.05). The mean plasma LH level did not change during the infusion of DHT alone, but it did increase significantly when Nal was added (DHT, 4.8 +/- 1.0; DHT + Nal, 7.9 +/- 1.0 IU/L; P less than 0.01). The results of this acute pharmacological study suggest that androgens may have two separate effects on the hypothalamic-pituitary axis: 1) inhibition of GnRH release, which appears to be mediated via opioid peptides, and 2) inhibition of pituitary LH secretion, which is not dependent on opioids.