Rapid naloxone-induced alterations of androgen variables in the growing male rat

Contrary to earlier views on the inability of naloxone to affect androgen variables by way of general circulation, systemically applied naloxone (2.5 mg/kg body weight, single i.p. or i.v. injection) has been shown to rapidly induce (within an hour) a significant fall (-35.7% on the average) of the concentration of serum androgen (testosterone and dihydrotestosterone; (T + DHT) in peripubertal rats (51-58 days old). Such a response to the opiate antagonist was absent, however, in low-androgen prepubertal animals (37-44 days old) and in those among peripubertal rats which still showed subcritical initial levels of androgen in circulation (less than 1.5 ng/ml; experiments with repeated blood sampling in catheterized animals). In peripubertal rats naloxone was also shown to induce a significant decrease (-36%) in basal in vitro androgen production by testes removed 15 or 30 min following the intraperitoneal administration of the opiate antagonist. Such an inhibitory effect on basal steroidogenesis has not been observed in control multiple-dose experiments in which incubated testes from naloxone-naive rats have been directly challenged with naloxone; on the contrary, enhancing direct effects were recorded, but only with the highest concentration of naloxone tested (10(-4) M). The possibility thus remains open that indirect inhibitory effects of injected naloxone may be operational in intact animals. Hypoprolactinemia, known to interfere in an age-dependent manner with the responsiveness of Leyding cells to luteinizing hormone (LH), may be of particular relevance.(ABSTRACT TRUNCATED AT 250 WORDS)