Baulieu E E, Lasnitzki I & Robel P. Metabolism of testosterone and action of metabolites on prostate glands grown in organ culture. Nature 219:1155-6, 1968

When we started our experiments on rat ventral prostate organ culture, the “dihydrotestosteronehypothesis” was in the air. It was known, from the work of several authors, Farnsworth, Kochakian, Ofner, Pearlman, and others, that testosterone (1) metabolites of the 5a-series are present in the rat ventral prostate and that dihydrotestosterone (DHT) is a potent androgen in vivo t llse Lasnitzki, working at the Strangeways Laboratories in Cambridge, reported in 1965 the action of T on the maintenance of ventral prostate explants in organ culture. She accepted our proposal to investigate the metabolism of 3 H-testosterone and the activities of identified metabolites, obtained in nonradioactive form from Roussel-Uclaf, in her culture system. Preliminary results were published in 1967. When our paper was released by Nature, the results of N. Bruchovsky and J.D. Wilson 2 and those of K.M. Anderson and S. Liao, 3 who reported the selective uptakeof DHT by prostate nuclei, had just appeared. Our results confirmed the local metabolism of T to DHT and the nuclear accumulation thereof. In addition, under identical experimental conditions, the marked “growth” stimulating property of DHT was observed. The reader interested in going through our paper in Nature will not find the word “dihydroteetosterone.” This was because the molecule 5a-androstane-17f3-ol-3-one had been routinely abridged androstan-ol-one by steroid chemists. Obviously, this name for the active metabolite of T was defeated, and 5a-dihydrotestosterone or DHT is the only one • in use nowadays. Those who requested reprints of our paper have received a remark “added in reprint” indicating that 5o-androstane-3j3, 17l3-diol (3(3-diol), which has been found as a metabolite of Tin the cytoplasm, did not provoke any cell division but could maintain cell height and secretion. We proposed that this compound had an activity different from that of DHT. The hypothesis of a dual mechanism of action of T involving two metabolites with different sites of action (nuclear for DHT, cytoplasmic for 3(3-diol) attracted considerable interest. However, when our culture system was improved by superfusion with a completely defined medium containing androgens in the nM range, the qualitative difference between DHT and 3(3-diol vanished, and the 3(3-diol activity was attributed to a slight conversion back to DHT (reviewed in reference 4). Indeed, a single molecular entity of androgen receptor has been defined and cloned. 5