Hyperplastic and adenocarcinomatous human prostatic tissue was superfused in vitro with radioactively labelled androst-4-ene-3,17-dione, testosterone and 5alpha-dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one), with and without addition of the anti-androgens cyproterone and cyproterone acetate. Cyproterone competitively inhibited the entry of the androgens into the majority of the tissues, whereas cyproterone acetate increased this entry. These findings indicated that transport of androstenedione, testosterone and 5alpha-dihydrotestosterone into prostatic tissue is performed by a specific mechanism, possibly involving a carrier situated in the cell membrane. The extent of metabolism of the three androgens was also modified: formation of 5alpha-dihydrotestosterone from testosterone, and of the latter from androstenedione, was decreased by cyproterone and increased by the acetate. Acetate was more effective than cyproterone in decreasing the ;uptake' of the perfused androgens by the tissue; at the same time, it increased the androgen clearance from the tissue. As cyproterone acetate is the more potent of the two anti-androgens, the possibility that these findings in vitro are related to the different anti-androgenic potency exhibited by the two compounds in vivo is discussed. ;Uptake' of the two anti-androgens and the response to their action on androgen dynamics were similar in adenocarcinomatous and hyperplastic glands.

Normal, hyperplastic and adenocarcinomatous human prostatic tissue was perfused in vitro with radioactively labelled androstenedione, testosterone and 5alpha-dihydrotestosterone with and without added oestradiol-17beta. Various parameters of tissue-steroid relationship were measured at the steady state. When oestradiol (0.11 or 0.22mumol/l) was added to the perfusing medium, the entry of the steroids into the tissue and their metabolism was increased in the majority of the glands studied. The ;uptake' of all the steroids varied, in response to the addition of oestradiol, in both normal and adenocarcinomatous glands in a way differing from the response of hyperplastic glands. As a consequence, the tissue clearance of the steroids, particularly of androstenedione and testosterone, increased in normal and adenocarcinomatous glands in the presence of oestradiol, and decreased in the hyperplastic tissues. At a concentration 0.33mumol/l, oestradiol decreased the entry of the steroids in all the tissues studied, while the clearance of steroids tended to decrease. The significance of these findings in terms of the regulation of androgen dynamics in vivo in the normal and diseased human prostate, with particular regard to the response to oestrogen treatment, is discussed.

An ultramicrochemical technique has been applied to the study of the metabolism in vitro of [3H]DHA in the separated adult and foetal zones of the human adrenal gland. Evidence has been found for the formation of DHA sulphate and androstenedione in the adult and foetal zone, and whole adrenal gland preparations obtained from one newborn hydrocephalic infant and two mid-term foetuses, and also for the formation of 1 1\g=b\-hydroxyandrostenedione in the adult zone tissue from the hydrocephalic infant.In all experiments, more DHA was converted to DHA sulphate by the foetal zone (21\p=n-\27 % conversion) than by the adult zone (5\ p=n-\ 7 % conversion), whereas more androstenedione was formed in the adult zone than in the foetal zone. At mid-term less than 0\m=.\6% of [3H]DHA was converted to androstenedione compared with 33 and 3\m=.\4 % conversion by the adult and foetal zone tissue, respectively, from the hydrocephalic infant.These results are discussed in relation to perfusion studies of the human foetus and previous in vitro and histochemical investigations of the human foetal adrenal gland.

SUMMARY The metabolism of [3H]pregnenolone and [3H]dehydroepiandrosterone ([3H]DHA) by tissue from the separated zones and whole adrenal glands from newborn anencephalic infants was investigated. Pregnenolone was metabolized by the whole gland homogenates mainly to pregnenolone sulphate and unconjugated 17α-hydroxypregnenolone and also to small amounts of DHA and dehydroepiandrosterone sulphate (DHAS). DHA was metabolized by the whole gland homogenates mainly to androstenedione and DHAS and small amounts of 11β-hydroxyandrostenedione. Adrenal gland tissue from a 42-week-old anencephalic infant containing three histologically distinct zones in the adult cortex in addition to residual foetal zone had sulphokinase, 17α-hydroxylase, 17–20 lyase and 3β-hydroxy-steroid dehydrogenase/Δ4,5 unsaturated isomerase activity in each of these zones. These enzymes were also present in the adrenal adult zone of another anencephalic infant. Omission of ATP from the incubation medium greatly reduced the conversion of DHA to DHAS in the homogenates and separated zones. These results are discussed in relation to oestrogen biosynthesis in anencephaly and to foetal 4-en-3-oxosteroid synthesis in utero.

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