Narcotics and the hypothalamic-pituitary-gonadal axix: acute effects on luteinizing hormone, testosterone and androgen-dependent systems.

The effects of narcotics on several aspects of the hypothalamic-pituitary-gonadal axis were examined in the male rat. Our results indicate that a large number of narcotics acutely depress serum luteinizing hormone levels and that these reduced gonadotropin levels lead to a subsequent fall (1-2 hours later) in serum testosterone levels. The luteinizing hormone-depleting effect of the narcotics appears to represent a specific narcotic action since the (-)-isomers of the narcotics were much more effective than the ()-isomers, naloxone antagonized their effects and tolerance rapidly developed. Further, our studies indicate that the impairment of the functional and structural integrity of the secondary sex organs produced by chronic narcotic administration is not due to a direct effect of these drugs since they have no effect on the uptake of subcellular distribution of testosterone in the secondary sex organs or on the androgen-dependent accumulation of myo-inositol. Consequently, it appears that the testosterone depletion produced by the narcotics is solely responsible for their adverse effect on the secondary sex organs. The results of these studies suggest that the effects of the narcotics on the hypothalamic-pituitary-gonadal axis are confined to either the hypthalamus or the pituitary gland.