Metabolism and receptor binding of nandrolone and testosterone under in vitro and in vivo conditions.

The metabolism and receptor binding of nandrolone (N) and testosterone (T) were studied under in vitro and in vivo conditions. The results of both in vitro incubation studes with 3H-N and 3H-T in tissue homogenates from rats and in vivo infusion studies with 3H-N and 3H-T in conscious rats show the importance of the enzymes 5 alpha-reductase and 3 alpha/beta-hydroxysteroid-oxidoreductases in the prostate and the importance of the enzyme 17 beta-hydroxysteroid dehydrogenase in the kidney for the effects of N and T on these tissues. Following infusion of a combined dose of 3H-N and 3H-T there is a preferential retention at the receptor of 5 alpha-dihydrotestosterone (DHT) over 5 alpha-dihydronandrolone (DHN), N and T (DHT much greater than DHN greater than N greater than T) in the prostate because T is a better substrate than N for 5 alpha-reductase and because DHT binds more strongly to the androgen receptor than DHN, N and T. In the kidney 5 alpha-reductase is not important; there is a preferential retention of N in T (DHN and DHT were only present in small amounts) because N is less susceptible than T for metabolic inactivation by the enzyme 17 beta-hydroxysteroid dehydrogenase and N binds strongly to the androgen receptor. Both in vitro and in vivo studies show that N and T were relatively stable in spleen, thymus and muscular tissue (only shown in vivo) and, as a result, the same amount of N and T was bound to the receptor in these tissues in the in vivo infusion experiment.(ABSTRACT TRUNCATED AT 250 WORDS)