Jo urno lo fS~e ro idBio rhrm r~rr:.~. 1972. Vol. 3, pp. 385-399. Pcrgamon Press. Printed in Great Britain zyxwvutsrqponmlkjihg THE TRANSFORMATION OF TESTOSTERONE INTO DIHYDROTESTOSTERONE BY THE BRAIN AND THE ANTERIOR PITUITARY R. MASSA;E. STUPNICKA. Z. KNIEWALD and L. MARTINI Department of Pharmacology. University of Milano, 32, Via Vanvitelli, 20129, Milano, Italy SUMMARY Slices of rat pituitary gland, hypothalamus, amygdala, cerebral cortex and prostate have been incubated in zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA vitro with labelled testosterone; the metabolites formed have been identified. Testosterone is converted into l7/3-hydroxy-So-androstan-3-one (androstanolone, dihydro testosterone, DHT) by all tissues examined. The prostate is the structure which effects such a conversion to the greatest extent; the pituitary gland and the hypothalamus are also very active; the cerebral cortex and the amygdala are also able to transform testosterone into DHT, but the rate of conversion is not as great as that found in the tissues previously mentioned. Androstenedione. 5a-androstan-3,17-dione and So-androstan-3a, 17/3-diol are also formed by some of the tissues. Castration increases and treatment with exogenous testosterone decreases the transformation of testosterone into DHT at the pituitary and the hypothalamic level. Both at the hypothalamic and the pituitary level, the addition in vitro of progesterone, 1 l-deoxycorti- costerone. I I-deoxycortisol and corticosterone reduces the transformation of testosterone into DHT; on the contrary, the addition of pituitary FSH increases the conversion of testosterone into its ‘active’ metabolite. The ability to transform testosterone into DHT is much higher zyxwvutsrqp in all structures examined (with the exception of the prostate) in prepuberal than in adult rats. INTRODUCTION RECENT evidence suggests that, in the cells of androgen-sensitive structures (prostate, seminal vesicles, etc.), testosterone is transformed into 17P-hydroxy- .5a-androstan-3-one (androstanolone, dihydrotestosterone, DHT) and 5a- androstan-3a, 17p-diol [ I]; the intracellular formation of these metabolites seems to be essential for the appearance of the androgenic activity[ 1,2]. If the formation of DHT and of Scz-androstan-3a,l7@-diol is a general feature of androgenic action, one might expect these derivatives to be formed also in the sites in which testosterone exerts its feedback effect on gonadotrophin secretion and influences sexual behaviour. This hypothesis was recently submitted to experimental verification in our laboratory. [14C]-labelled testosterone was incubated in vitro with slices of hypothalamus (basal part, including the median eminence region), pituitary gland, amygdala, cerebral cortex, prostate and seminal vesicles, taken from different groups of male rats of the Sprague-Dawley strain. After three hours of incubation the metabolites formed were extracted from the incubation medium, purified and identified using procedures which have been described previously [3]. RESULTS AND DISCUSSION Experiments in normal adult animals The results obtained indicate that testosterone is converted into DHT by all tissues examined; however, the rate of conversion appears to vary considerably from tissue to tissue (Table 1). The formation of DHT occurred to a very large extent in the two peripheral androgen-dependent structures (prostate and seminal 385