INHIBITION OF THE TESTOSTERONE-METABOLISM IN RAT-LIVER SLICES BY 17-ALPHA-ESTRADIOL

The influence of 17a-estradiol (CAS 57-91-0), a hormonally almost inactive isomer of physiological 17-beta-estradiol, on the metabolism of [C-14]-labeled testosterone in rat liver slices was investigated. The analysis of extracts from incubates (3.0 ml medium, 100 mg liver slices, 416 nmol [C-14]-testosterone, 0.1-30-mu-g 17a-estradiol, 37-degrees-C, 30 min) by thin layer chromatography showed, that 30-mu-g of 17a-estradiol inhibited the testosterone turnover in liver slices of female animals. The failure of a significant inhibitory effect in liver slices of male animals is attributed to the known, much smaller total turnover of testosterone in male liver cells. The amount of unchanged 4-en-3-oxo-steroid (testosterone and 4-androstene-3,17-dione) was increased by a factor of 2.65 and 2.25, respectively. With high probability, the inhibition was the result of a decreased hydrogenation of testosterone to dihydrotestosterone (DHT, 17-beta-hydroxy-5a-androstan-3-one), catalyzed by 5a-reductase, since the production rates of DHT and the DHT-transformation metabolites (5a-androstane-3a,17-beta-diol and 5a-androstane-3,17-dione) were significantly lowered (factors: 0.16, 0.61, 0.61, respectively). In further experiments 17-beta-estradiol and 17a-ethinylestradiol could be shown to inhibit the testosterone turnover in liver slices of female rats, too, but to a lower extent than 17a-estradiol (relative inhibitory effects: 17a-estradiol:17-beta-estradiol:17a-ethinylestradiol = 100:73:58). Accordingly, the inhibitory effect of the tested estrogens was inverse to their hormonal potency. On the whole, the results indicate that the therapeutical efficacy of topically administered estrogens in the therapy of dermal diseases related to the effects of enhanced amounts of dermally formed DHT might be based on an inhibition of the local 5a-hydrogenation of testosterone.