THE EFFECT OF ANABOLIC-ANDROGENIC STEROIDS ON AROMATASE-ACTIVITY AND ANDROGEN RECEPTOR-BINDING IN THE RAT PREOPTIC AREA

The level of aromatase in the preoptic area of rats is transcriptional ly regulated through a specific androgen-receptor mediated mechanism a nd can be used as a measure of central androgenic effect. Therefore, s everal commonly abused anabolic-androgenic steroids (AAS) were tested for their ability to induce aromatase activity in the preoptic area of castrated rats. In addition, we determined the relative binding affin ities of these compounds for the androgen receptor, as well as their a bility to bind androgen receptor in vivo following subcutaneous inject ions. All of the AAS compounds tested significantly stimulated POA aro matase activity above castrate levels. The compounds that produced the greatest stimulation of aromatase activity were those that bound most avidly to the androgen receptor in vitro (i.e., testosterone, dihydro testosterone and nandrolone). In contrast, the 17 alpha-alkylated comp ounds that were tested (stanozolol, danazol, methandrostenolone) modes tly stimulated aromatase and were weak competitors for the androgen re ceptor. The subcutaneous injection of AAS compounds increased the conc entrations of occupied nuclear androgen receptors in the brain, but th e magnitude of effect was not related to their potency for inducing ar omatase or their relative binding affinity for the androgen receptor s uggesting that androgen receptor occupancy in POA is not correlated wi th the action of androgen on aromatase. The present results help expla in the behavioral effects of AAS compounds in rats. (C) 1998 Elsevier Science B.V.