Comparison of maternal serum and urinary oestrogen determinations as indicators of fetal well-being.

Serum oestrogen concentration and urinary oestrogen excretion were measured in 134 women in the last trimester of pregnancy. An automated fluorimetric method was used for urinary oestrogens and a radioimmunoassay which measures both free and conjugated oestrogens, with the exception of sulphates, was employed for serum. Pregnancies were classified into a 'normal' or 'abnormal' group according to the clinical state of the baby at birth. The range of values for both serum and urinary oestrogens was wide at each stage of gestation and the mean values in the two groups were not significantly different. It was concluded that for a valid indication of fetal well-being serial determinations were essential, and that serum and urinary oestrogens were of comparable predictive value. Expressing the urinary results in terms of creatinine excretion did not improve their predictive value.

Studies on androgen transport into canine prostate in vitro.

Slices from canine prostate were superfused with [17alpha-3H] testosterone and 5alpha-dihydro[1,2-3H]testosterone at 'physiological' concentrations; to some wuperfusions, either [3H]cyproterone or [3H]cyproterone acetate was also added. The following parameters were measured: 'uptake' of anti-androgen by the tissue, rate of entry of testosterone and 5alpha-dihydrotestosterone into the tissue, rate of efflux from the tissue of 5alpha-dihydrotestosterone and concentration of 'diffusible' 5alpha-dihydrotestosterone in the slices. The adsorption of steroids on to the surface of the slices and the bulk flow of tritiated water into the slices were also investigated. It was concluded that these two factors did not interfere with the measurement of entry and efflux of the androgens. Cyproterone and cyproterone acetate were not metabolized, but were concentrated in the slices to many times the level in the medium. With rate of supply of anti-androgens up to 43 pmol/min, their uptake increased together with the rate of entry of the two androgens and the rate of efflux of 5alpha-dihydrotestosterone. At a higher rate of supply of anti-androgens, their uptake and the rates of entry and efflux of the androgens decreased sharply. In most cases, the inward movement of 5alpha-dihydrotestosterone into the slices took place against a negative concentration gradient, while that of testosterone always occurred down a positive concentration gradient. These results confirmed the hypothesis already put forward that 'carriers' involved in the transport of androgens are present in the membrane of prostatic cells (Giorgi, Moses, Grant, Scott & Sinclair, 1974). Non-specific and specific intracellular binding, exhibiting greater affinity for 5alpha-dihydrotestosterone than for testosterone, was demonstrated in canine prostate by means of 'washing-out' experiments. On the basis of its affinity for androgens and the presence of inhibition by low concentrations of anti-androgen, intracellular binding seemed to be due to components distinct from the postulated membrane 'carriers'.

Androgen dynamics in vitro in the human prostate gland. Effect of cyproterone and cyproterone acetate.

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.

Androgen dynamics in vitro in the human prostate gland. Effect of oestradiol-17 .

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.

Androgen dynamics in vitro in the normal and hyperplastic human prostate gland.

The dynamics of uptake and metabolism in vitro of androgens by normal and hyperplastic human prostate glands was studied by means of a new experimental design proposed by Gurpide & Welch (1969). Prostate slices were perfused with a medium containing [(3)H]testosterone and [(14)C]androstenedione, or 5alpha-dihydro-[(3)H]testosterone and [(14)C]testosterone. The entry into the slices, the irreversible metabolism, the conversion between the compounds and the tissue retention or ;uptake' of the steroids were measured at the steady state. A similar portion of the three androgens entered the tissue and was irreversibly metabolized. Conversion of testosterone into 5alpha-dihydrotestosterone was much greater than the interconversion of testosterone and androstenedione. The prostate slices retained 5alpha-dihydrotestosterone at a concentration three times that in the medium, whereas testosterone and androstenedione were retained to a smaller extent. At a steroid concentration of 0.11mumol/l in the medium, the various parameters did not differ significantly in experiments performed with slices from normal and hyperplastic glands. When the steroid concentration in the medium was increased tenfold, however, a difference between normal and hyperplastic glands was evident. The normal glands increased the uptake and metabolism proportionally to the elevation of the steroid concentration in the medium. In the hyperplastic glands the entry and metabolism lagged behind the increase in steroid supply, whereas the tissue uptake became disproportionately high. The possible causes of this finding are discussed.