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

Abstract

Abstract. 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 5α-reductase and 3α/β-hydroxysteroid-oxidoreductases in the prostate and the importance of the enzyme 17β-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 5α-dihydrotestosterone (DHT) over 5α-dihydronandrolone (DHN), N and T (DHT ⪢ DHN > N > T) in the prostate because T is a better substrate than N for 5α-reductase and because DHT binds more strongly to the androgen receptor than DHN, N and T. In the kidney 5α-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 17β-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. In vitro binding studies with the androgen receptor in intact human cells show that 5α-reduction increases the affinity of T and decreases the affinity of N and of the 17α-ethyl derivative of N (3-keto-ethylestrenol). The results of the present studies explain the relatively strong effect of N, or derivatives of N, compared to that of T on tissues devoid of 5α-reductase activity (e.g. muscular tissue) and they suggest that in particular there may be a strong effect of N on tissues which in addition have a high 17β-hydroxysteroid dehydrogenase activity (e.g. kidney).