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The prostates of 41 foetuses and neonates have been assayed for testosterone, 5 alpha-dihydrotestosterone (DHT), oestradiol and oestriol and the presence of these hormones has been demonstrated in all cases. Oestriol was found to be present in the highest concentration. A highly significant correlation was found between testosterone and DHT as well as between DHT and oestradiol. The correlation between oestriol and oestradiol was also significant. It has been pointed out that the presence of these hormones is essential for the growth and development of the prostate gland.

Serum concentrations of testosterone (Tser), 5 alpha-dihydrotestosterone (DHT), and free testosterone (Tsal) in saliva were determined in 117 healthy young men between the ages of 20 and 30. A battery of standardized tests and projective techniques were administered simultaneously in order to measure various components of aggression, including sexual aggressiveness. All three androgens show reliable positive correlations with self-ratings of spontaneous aggression. Dominance exhibits a positive, statistically significant correlation to Tser and to DHT. In addition, DHT is negatively related to the scale restraint of aggression. These results support previous findings about Tser and point to the importance of other androgens--especially DHT--for this aspect of endocrine-affect relationships. Interest in sexual aggression yielded no significant results for Tser and DHT (Tsal shows a low positive correlation). The ratio DHT/Tser, however, correlates significantly with this component of aggression.

It is now well established that chronic treatment with GnRH agonists offers an advantageous alternative to orchiectomy and estrogens for the treatment of prostate cancer. Castration levels of androgens can thus be easily achieved without side effects other than those related to castration levels of serum androgens. However, man is unique among species in having a high secretion rate of precursor adrenal steroids which are converted into active androgens in the normal prostate and prostatic cancer. All the enzymes required for the transformation of dehydroepiandrosterone sulfate, dehydroepiandrosterone, androstenedione, and androst-5-ene-3 beta, 17 beta-diol are present in prostatic tissue. Moreover, as shown in many systems, castration levels of serum testosterone (T) at 0.2-0.4 ng/ml exert significant androgenic activity in target tissues. In order to inhibit the action of androgens of both testicular and adrenal origin, GnRH agonists have been administered in association with the pure antiandrogen Flutamide in patients having clinical stage D2 (bone metastases) prostate cancer. A positive objective response assessed according to the criteria of the United States National Prostatic Cancer Project (USNPCP) has been observed in 84 of the 88 patients who had received no previous treatment (95.4%). After 2 yr of treatment, the probability of continuing response is 70% compared to 0-10% by previous approaches. In addition, the death rate at 2 yr is at 10.9% as compared to approximately 50% after standard hormonal therapy. When the same treatment was applied to patients who had received previous hormonal therapy (orchiectomy, estrogens or GnRH agonists alone) before showing a relapse, the response rate decreased to 62.9% and the death rate at 2 yr was 52%.(ABSTRACT TRUNCATED AT 250 WORDS)

A technique for the measurement of five conjugated steroids (dehydroepiandrosterone sulphate, pregnenolone sulphate, testosterone sulphate, dihydrotestosterone sulphate and testosterone glucuronide) in human seminal plasma is described. The steroid sulphates and testosterone glucuronide were measured by radioimmunoassay after solvolysis and enzyme hydrolysis, respectively. In all cases the recognized criteria of assay reliability were fulfilled. In a group of men with established fertility, dehydroepiandrosterone sulphate had the highest concentration and testosterone sulphate had the lowest (mean levels of 1-04 mumoles/1 and 1-52 nmoles/1, respectively). The levels of pregnenolone sulphate, dihydrotestosterone sulphate and testosterone glucuronide were 30-3, 4-37 and 38-8 nmoles/1, respectively. In all cases the levels of conjugated steroid exceeded the levels of the corresponding unconjugated compound.

Dihydrotestosterone levels in maternal and fetal plasma were unchanged from midpregnancy to term whereas the values in amniotic fluid increased by 75%. There were no sex differences in fetal plasma or amniotic fluid values throughout pregnancy in contrast to the results reported for testosterone levels.

To analyze the possible correlation between steroidogenic activity of the Leydig cells and their morphology and ultrastructure in the boar testes at different ages, testes from six Yorkshire boars were obtained by orchidectomy at 8,14,28,40,70,78,86,94 and 100 days of age. Using representative sections of testicular parenchyma, light as well as transmission electron microscopic studies were performed. Homogenized, albuginea-free tissue was further used for quantitative estimation of total proteins and metabolic pools of androstenedione (A), testosterone (T) and 5 alpha-dihydrotestosterone (DHT). Under light microscopy, abundant hyperplastic Leydig cells were observed from 14 to 40 days, thereafter was a decrease in their size and number. Spermatogenesis remained in the spermatogonia stage while the tubules increased in diameter until age 80 days; from 90 days on, pachytene primary spermatocytes could be found. A well developed smooth endoplasmic reticulum was observed in Leydig cells from the 8th postnatal day. Metabolic pools from age 8 to 28 days showed a decrease for T and A from 4.33 to 1.78 and 2.51 to 0.48 microgram/mg protein respectively, maintaining thereafter the same levels throughout the age-span studied. However, DHT was found at low levels from the beginning of neonatal period (from 0.07 to 0.38 microgram/mg protein).

The immunocharacteristics of androgen target cells in the anterior pituitary of male rats are assessed by a combined thaw-mount autoradiography and immunoperoxidase staining method permitting the simultaneous identification of steroid-hormone target cells and protein or polypeptide hormone-producing cells in the same preparation. After injection of 3H-dihydrotestosterone, nuclear concentration of radioactivity is observed in cells of the anterior lobe, in "ectopic" cells in the intermediate and posterior lobes as well as in certain pituicytes. The radioactively labeled cells in the anterior lobe are identified immuno-histochemically as gonadotropes and thyrotropes with the use of antiserum to ovine LH or its subunit beta-LH and bovine beta-TSH. The results suggest genomic effects of androgen on gonadotropes and thyrotropes as well as pituicytes.

The effect of sodium 4-methyl-3-oxo-4-aza-5 alpha-pregnane-20(s)-carboxylate (4-MAPC) on testosterone metabolism was investigated in rat and human prostates in organ culture. The general properties of the test system for androgen metabolism and response to inhibitors were in close agreement with in vivo observations. As an inhibitor of prostatic tumor 5 alpha-reductase, 4-MAPC was equally as effective as 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one, reported to be a potent 5 alpha-reductase inhibitor. Inhibition of 5 alpha-reductase activity by 4-MAPC, but not by 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one, was accompanied by concomitant stimulation of 17 beta-oxidation of testosterone. This differential effect was observed in explants of human prostatic carcinoma and benign prostatic hypertrophy containing a relatively high degree of glandular hyperplasia. It was also seen in explants of dorsolateral rat prostate but not in the ventral prostate. 4-MAPC exhibited low affinity for rat prostatic cytosol 8S androgen receptor. Steroid extraction of purified nuclei from inhibited rat tissues revealed substantial amounts of radioactivity derived from [3H]testosterone cochromatographed with other metabolites in addition to dihydrotestosterone. The endocrine changes produced by this inhibitor of 5 alpha-reductase are reconcilable with the responsiveness of androgen-sensitive malignant prostatic cells to hormonal therapy.

The concentrations of progesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone and androsterone were determined in tissue samples from the human hypothalamus, anterior pituitary, pineal, amygdala and parietal cortex, taken at autopsy from male (n = 4) and female cadavers (n = 4) of various ages. The measurements were performed using radioimmunoassays for the individual steroids after the chromatographic purification of solvent extracts of tissue samples on Lipidex-5000TM. Preliminary qualitative analyses of the chromatographic profiles of various steroids by radioimmunoassay demonstrated the presence of these steroids in various regions of the brain, but an immunoreactive peak corresponding to 17-hydroxyprogesterone was not found. The concentrations (ng/g tissue wet wt.) of all steroids measured were either very low or below the limit of detection in brain tissues taken from male and female infants. In the adult brain, there was no difference in the distribution of steroids between the various regions studied. There was no sex difference in the brain tissue steroid concentrations, with the exception of testosterone which was clearly much higher in brain tissues from men as compared to women. Although testosterone was undetectable in most samples taken from adult women. 5 alpha-dihydrotestosterone could be measured in almost all samples, which suggests that this is the most important androgen in the human brain. When brain tissue steroid levels are compared with serum concentrations, it can be postulated that a state of equilibrium exists between the fraction of serum steroids which are not bound to high-affinity binding proteins and the amount of steroids in brain tissues.

The seminal vesicles of African catfish, Clarias gariepinus, can produce at least seven different steroid glucuronides, especially during the breeding season. In the present experiments quantification of the seven compounds and their free steroids was carried out by means of gas chromatography-mass spectrometry in particular by selected ion monitoring, using seminal vesicle fluid of African catfish collected in the Hula nature reserve (Israel) and from a nearby fish farm. Some of the feral fish were in spawning condition; the others and the pond fish were in nonspawning condition. Compared to the nonspawning groups, in the feral spawning animals a significantly higher level was found especially of 5 beta-pregnane- 3 alpha,17 alpha-diol-20-one-glucuronide, but also of 5 beta-androstane-3 alpha,17 beta-diol-glucuronide, 5 beta-androstane-3 alpha,17 beta-diol-11-one-glucuronide, and 5 beta-pregnane-3 alpha,17 alpha-diol-20-one. The feral and pond nonspawning groups mainly differed in a signficantly higher concentration of 5 beta-pregnane-3 alpha,17 alpha-diol-20-one-glucuronide in the feral nonspawning fish. For the levels of etiocholanolone, testosterone, 5 beta-androstane-3 beta,17 beta-diol, and their glucuronides no significant differences were observed between the three groups, and 5 beta-dihydrotestosterone and its glucuronide could not be detected in the seminal vesicle fluid of any of the animals. The increase in the concentration of three 5 beta-reduced steroid glucuronides may point to a pheromonal function of one or more of these compounds, as demonstrated for the entire steroid glucuronide fraction of the seminal vesicle fluid. Experiments are being carried out to verify this hypothesis.

A macromolecular component which specifically binds tritium-labeled-dihydrotestosterone is present in cultured amniotic fluid cells. The androgen-binding complex is characterized by a 3.6S sedimentation coefficient, an apparent dissociation constant of 1 nmol/L, a mean binding capacity of 243 +/- 140 fmol/mg of DNA, and a specificity for testosterone and dihydrotestosterone. Similar properties have been reported for the androgen receptor of the fetal genital skin fibroblast, which suggests that the tritium-labeled-dihydrotestosterone-binding component in amniotic fluid cells is the androgen receptor. Amniotic fluid cell monolayers incubated with serum-free medium containing testosterone are able to transform testosterone into dihydrotestosterone. The 5 alpha-reduced product has been characterized by thin-layer chromatography and capillary column gas-liquid chromatography. Androgen receptors and 5 alpha-reductase activity are expressed in amniotic fluid cells. The prenatal diagnosis of 5 alpha-reductase deficiency or complete androgen insensitivity syndrome (testicular feminization) is thus theoretically possible and obviously prenatal testing would be indicated in the family at high risk.

Concentrations of testosterone, dihydrotestosterone, androstenedione, progesterone, 17 alpha-hydroxyprogesterone, and estradiol were measured by radioimmunoassay in the amniotic fluid and maternal peripheral blood obtained from normal pregnancies between 14 and 40 weeks of gestation. There was a sex difference in the levels of all the androgenic steroids in the amniotic fluid before 20 weeks with higher levels in pregnancies with male fetuses. Amniotic fluid 17 alpha-hydroxyprogesterone levels were significantly elevated in a pregnancy with the fetus affected with congenital adrenal hyperplasia. The levels of all the steroids in the amniotic fluid were significantly elevated in the pregnancy with molar degeneration of the placenta. There was a sex difference in the levels of dihydrotestosterone in the maternal peripheral blood before 20 weeks with higher levels in pregnancies with male fetuses. There was no correlation between the steroid levels in the maternal serum and amniotic fluid even though most of the samples of maternal serum were drawn at the same time as amniocentesis.

In the biochemical evaluation of hirsutism, 50% or less of patients have an elevated total serum testosterone. Recent work has suggested that measuring salivary testosterone or a derived serum 'free testosterone index' may be of use in the evaluation of hyperandrogenism. We have measured serum total, derived serum free indices and salivary concentrations of testosterone and 5 alpha-dihydrotestosterone in an unselected group of hirsute patients in order to assess their value in the routine evaluation of hirsutism. The assays were performed using a novel oxidation procedure to overcome the need for chromatographic separation. The 'free testosterone index' gave the best discrimination. Salivary androgen concentrations were comparatively poor and cannot be recommended for routine use.

Cytosolic androgen receptor levels were measured in different brain regions of fetal male and female rhesus monkeys (day 135 post-conception). The hypothalamus-preoptic area, amygdala and cerebellum exhibited higher receptor concentration in comparison to the cerebral cortex (parietal, temporal frontal, and occipital lobes), hippocampus and cingulate gyrus (P less than 0.001). No sexual difference in receptor concentrations was found except in the amygdala where fetal males exhibited slightly higher levels than females. The similarity in androgen receptor levels suggests that the developing brain of both sexes could be influenced by circulating androgens under normal or pathological conditions.

Permanent transplantable human tumors in nude mice offer the possibility of studying the impact of different (endocrine) treatment regimens on human cancer tissue. Among the limited number of human tumor models in athymic nude mice developed so far, the PC-82 tumor (which was established in our institution) mimics many of the important properties of clinical prostate cancer. The absence of PC-82 tumor growth in intact female and in castrated male mice indicates the absolute requirement of androgen for the growth of this tumor. Delayed testosterone (T) substitution (up to 70 days after tumor grafting) in PC-82 transplanted female mice resulted in tumor growth. This indicated that after androgen withdrawal at least part of the cells do not die and keep the capability to respond to androgens. Androgen withdrawal from T-implanted tumor-bearing female mice caused a rapid reduction (90% within 1 day) of the tissue T and a slower decline (up to 90% within 7-10 days) of tissue DHT concentrations. By the use of Silastic implants, containing different proportions of T mixed with cholesterol, circulating T levels of 0.2-20 nmol/L were obtained. It was observed that a constant plasma T level between 1 and 2 nmol/L (achieved with 10% T implants) is the threshold below which growth of the PC-82 tumor tissue is no longer stimulated.

Among women with 46,XY gonadal dysgenesis, there is a high incidence of gonadal tumors. Because of evidence of a connection between occurrence of those tumors, H-Y phenotype, and breast development, we surveyed 55 cases of 46,XY gonadal dysgenesis and 12 related cases involving chromosomal and/or skeletal abnormalities. Our survey, including three new cases presented here, indicates that H-Y phenotype but not breast development may be related to the development of the gonadoblastoma-dysgerminoma. Thus among women with 46,XY gonadal dysgenesis, there are H-Y- and H-Y+ classes, but gonadal tumors are found almost exclusively in the H-Y+ class. Yet one of our patients may represent an exception to the association of H-Y+ phenotype and gonadal tumors in this syndrome.

The side gland of Suncus murinus is composed of well-developed sebaceous glands in both males and females. We measured the 5 alpha-reductase activity, androgen receptor content, and the intranuclear concentrations of testosterone and dihydrotestosterone in this side gland taking it as a new experimental model of human sebaceous glands. Lineweaver-Burk plot analysis suggested the presence of two classes of 5 alpha-reductase with different Km for testosterone in the homogenate. The enzyme activity was slightly higher in males than in females in the presence of a high concentration of testosterone. The levels of androgen receptors were approximately 40 and 30 fmol/mg protein in the cytosol and nuclei, respectively. The values did not differ significantly between males and females. The intranuclear concentration of dihydrotestosterone in the side gland was higher than that of testosterone in each sex. The intranuclear level of each of these two androgens in the female side gland was comparable to that in the male side gland despite the fact that the serum level of testosterone was much lower in the female. These data clearly indicate that the side gland is a typical target tissue for androgens in the female as well as in the male. Androgens other than testosterone may serve as precursors of dihydrotestosterone in the female side gland.

A method for simultaneously determining concentrations of major androgens in prostate has been developed. Extraction techniques used to isolate the androgens from minced tissue include homogenization with high-speed blades in Delsal's solvent mixture, adsorption to silica gel, followed by column and one thin-layer chromatography (TLC). Radioimmunoassays (RIA) of small aliquots of TLC eluates are used to quantitate picogram amounts of 5alpha-dihydrotestosterone (DHT) and 5alpha-androstanediols (Diol) and to estimate testosterone (T) and androstenedione (Ad). Contamination of blanks was reduced to RIA sensitivity limits primarily by treatment of glassware in a self-cleaning oven. The specificity of the method for each androgen was established by TLC separations of known prostate metabolites, antisera specificities, and parallelism of sample aliquots to androgen RIA standards. The overall precision, in terms of coefficients of variation, was 21% for DHT and 24% for Diol. T and Ad could not be measured with acceptable precision because their very low concentrations in prostate (less than or equal 0.5 ng/g tissue) were less than RIA sensitivity limits. Accuracy studies indicated recoveries ranging from 96% for Diol to 121% for DHT. In human benign hypertrophic prostate tissue, DHT averaged 153 ng/g soluble protein (5.8 ng/g tissue) which was 17 times higher than values obtained in human spleen and kidney; Diol in prostate showed no consistent differences from values noted in kidney or spleen.

We transplanted a pilosebaceous tumor developed on the sidegland of Suncus murinus to male nude athymic (BALB/c-nu/nu) mice. This tumor can be transplanted to female hosts as well, with a lower rate of graft-taking and slower growth rate. In this study we demonstrated the presence of macromolecules which specifically bind to estrogen. Measurement of 17 beta-estradiol (E2) binding by a dextran-coated charcoal assay revealed that the number of binding sites and the dissociation constant were 22.3 +/- 4.6 fmol/mg protein and 1.4 +/- 0.24 X 10(-9) M, respectively. This binding was specific for E2 and diethylstilbestrol (DES). Sucrose gradient centrifugation of the [3H]E2-labeled cytosol yielded a sharp peak of radioactivity at 3.5S-4S under high salt conditions and a 9S peak with a shoulder at 3.5S under low salt conditions. This 3.5S shoulder was due to dissociation of [3H]E2 from the 9S peak during the centrifugation, since only the 9S peak was obtained by postlabeled density gradient analysis. An assay of the in vivo binding of [3H]E2 showed significant radioactivity in the nuclear extract from the tumor. This nuclear uptake was markedly decreased by simultaneous administration of 100-fold excess of E2. In tumor-bearing castrated nude mice, 1-100 micrograms/day of E2 did not affect tumor growth, whereas it counteracted the stimulative effect of testosterone propionate.

Depot medroxyprogesterone acetate (D-MPA, 250 mg) and testosterone enanthate (TE, 200 mg) were administered twice with a 4-week interval to nine healthy men, and the levels in blood of steroids, gonadotrophins, lipoproteins, sex hormone binding globulin (SHBG) and prostaglandins (PGs) were measured, as well as steroid levels in semen and the sperm count and motility. The hormones analysed were: MPA, testosterone, androstenedione (A), dihydrotestosterone (DHT), oestradiol (E2), cortisol (C), luteinizing hormone (LH), follicle stimulating hormone (FSH) and the sulphoconjugated forms (-S) of testosterone, DHT, pregnenolone (5-P) and dehydroepiandrosterone (DHEA). Peak values of MPA (10.2 +/- 4.6 nmol/l) and testosterone (28.0 +/- 10.0) were found in the first blood samples 2 days after each injection. Thereafter the levels of MPA decreased gradually and reached the limit of detection 18-20 weeks after the second injection. Blood levels of testosterone fell sharply from the peak values and were grossly subnormal 2 weeks after each injection; levels did not return to pretreatment values during 24 weeks of follow-up. The pattern of change of DHT, A, E2 and sulphonated androgens was similar to that of testosterone. These data suggest that D-MPA and TE are absorbed at similar rates, and that the TE is metabolized rapidly. The subsequent reduction in the levels of A, testosterone-S and DHT-S was less marked and reached pretreatment values earlier than did the testosterone levels. No obvious changes were found in the levels of C, 5-P-S and DHEA-S or in the seminal plasma levels of the various steroids studied. The blood levels of LH and FSH fell precipitously 2 days after the first injection, then started to increase 4 weeks after the second injection to reach pretreatment values 12 weeks later. Of the lipoproteins studied only the levels of HDL-cholesterol and SHBG were found suppressed after treatment. Severe oligozoospermia and the complete absence of progressively motile sperm, in at least one semen sample, was observed in all subjects at 3-7 and at 5-16 weeks, respectively, after the last injection, suggesting that the men were infertile for at least 1 month after treatment. A spurious increase in the PG content of semen was also observed. In spite of the low blood testosterone levels, no subject reported changes in sexual behaviour or other signs of anabolic imbalance during or after the study. However, the increase in levels of E2 in some individuals should be kept in mind as a possible cause of side-effects.(ABSTRACT TRUNCATED AT 400 WORDS)

The measurement of androgen receptor and 5 alpha-dihydrotestosterone (DHT) levels in prostatic carcinoma may be of value in predicting responsiveness to anti-androgenic therapy. A sufficient amount of prostatic carcinoma tissue must be removed for measuring androgen receptor and DHT levels. We have studied the usefulness of Kaplan cold punch-resection compared with electroresection for obtaining tissue in 29 cases of enucleated benign prostatic hyperplasia. DHT level in electroresected specimens was similar to controls. However, following low, moderate, and high-power electroresection an average of total R1881 binding sites (Bmax) of electroresected specimens was reduced to 82.2, 71.9, and 52.1 per cent of corresponding controls, respectively. In contrast, the per cent decrease of Bmax of Kaplan cold punch-resected specimens was only 10 per cent of the control. From our data, Kaplan cold punch-resection of the prostate appears to be a useful tool for obtaining tissue suitable for measuring androgen receptor levels.

Sex steroids and 5-en-3 beta-hydroxysteroids were determined by radioimmunoassay in specific regions of the human brain, in the anterior and posterior pituitary, in one sensory organ, the retina and in the cranial nerves. Progesterone, androstenedione, testosterone and estrone were found in all areas of the brain and in all the cranial nerves but not in all cases. There was no sex difference except in the case of androstenedione where values were higher in women in some brain areas. Estrone values were always higher than those of estradiol in both men and women. No 5 alpha-dihydrotestosterone was detected in any of the samples studied. The values for pregnenolone, dehydroepiandrosterone and their sulfates were much higher than those of the sex steroids in all areas of the brain and in all the cranial nerves. Values for pregnenolone were greater than those of its sulfate while those of dehydroepiandrosterone were in general equal to or higher than those of its sulfate. The values for pregnenolone were greater than those of dehydroepiandrosterone. There were no obvious regional differences in the concentrations of the 5-en-3 beta-hydroxysteroids either in specific areas of the brain or in the cranial nerves. But there was a definite trend for the free dehydroepiandrosterone values to be higher in women. The possible significance of these observations is discussed.

Steroid receptors in endometriosis and adenomyosis were investigated to clarify their clinical significance. The receptor levels were determined by Scatchard plot analysis (4 degrees C, by dextran-coated charcoal). In the cytosols of both tissues, the 17 beta-estradiol-estrogen receptor (ER) complex demonstrated a dissociation constant (Kd) of 4.5 x 10(-10) M; the Kd of the progesterone-progesterone receptor (PR) complex was 1.5 x 10(-9) M; and the Kd of the dihydrotestosterone-androgen receptor (AR) complex was 4.0 x 10(-10) M. Seven cases of ovarian endometriosis were studied. The ER and PR levels in endometriosis seemed to be lower than those in the corresponding normal endometrium. AR was also present. There was a suggestion that most endometriosis is least responsive to progestogens. Ten cases of adenomyosis were studied. Histologic dating revealed a delay in the most aberrant endometrial tissue in adenomyosis, as compared with dating of corresponding normal endometrial tissue. ER and AR were detected in all cases. PR was not detected in some cases and, when detected, the content seemed to be lower, possibly suggesting the delayed dating.

Rams were randomly assigned to an experiment that evaluated effects of treatment (2.5 mg melatonin/d for 45 d vs control; MEL vs CON) in mid-May through June on testis weight and concentration of epididymal androgen receptor in July or September (Sept). Mean testis weight of MEL and CON rams was not different in July (332 vs 283 g), but in Sept was less (P less than .05) for MEL rams than CON rams (268 vs 382 g). Testis weight of MEL rams was less (P less than .05) in Sept than in July. Caput, corpus and cauda epididymal tissues were used to prepare extracts which were analyzed for concentration of dihydrotestosterone (DHT) receptor using a new standard curve method. A standard extract was characterized using four independent 8-point Scatchard analyses and found to contain 6.0 fmol DHT receptor/mg wet tissue (Ka = 3.5 X 10(8).M-1); this extract was used to establish standard curves for assays of unknown samples. Data on concentration of DHT receptors measured by Scatchard analysis and the standard curve method were highly correlated (r = 0.99; P less than .01; n = 8). Concentrations of DHT receptor were not affected by treatment, month of castration, or their interaction. However, for data pooled across treatment and month, concentration (fmol/mg protein) of DHT receptor was greater (P less than .05) in caput or corpus (125 or 122) than in cauda (92) epididymidis. The regional distribution of epididymal DHT receptors in this study confirmed our previous findings.(ABSTRACT TRUNCATED AT 250 WORDS)

To explore the relation between androgens and prostatic hypertrophy in man, the concentrations of testosterone, dihydrotestosterone, and androstenedione and the rate of conversion of testosterone to dihydrotestosterone have been measured in normal and hypertrophic prostate tissue. First, a double isotope derivative technique was adapted for the measurement of tissue androgen content in 15 normal and 10 hypertrophic prostates. Although there was no significant difference in the content of androstenedione and testosterone between the two types of tissue, the content of dihydrotestosterone was significantly greater in the hypertrophic tissue (0.60 +/-0.10 mug/100 g) than in the normal glands (0.13 +/-0.05 mug/100 g). Second, a regional study was performed in three normal prostates and four glands with early hypertrophy, and it was demonstrated that the dihydrotestosterone content was two and three fold greater in the periurethral area where prostatic hypertrophy usually commences than in the outer regions of the gland. Finally, the rate of conversion of testosterone to dihydrotestosterone has been measured under standardized conditions in tissue slices from 4 normal and 20 hypertrophic prostates. There was no significant difference in the rate of dihydrotestosterone formation between the two types of gland (6.0 +/-0.8 and 7.8 +/-0.5 mumumoles/15 mg of tissue per hr). While the mechanism by which dihydrotestosterone accumulation occurs remains unexplained, it is possible that the local accumulation of dihydrotestosterone may be involved in the pathogenesis of prostatic hypertrophy in man.

Three types of studies have been performed in immature, mature, and hypertrophic prostate glands of the dog. First, the concentrations of testosterone and dihydrotestosterone have been measured in the three types of gland. Dihydrotestosterone was the predominant hormone recovered in all prostates studied and was present in approximately five times higher concentration in the hypertrophic as compared to the other types of dog prostate. Second, pharmacological doses of dihydrotestosterone were administered to castrated dogs for 9 months and resulted in a distinct acceleration of prostatic growth as compared to testosterone treatment. Third, the rates of formation and degradation of dihydrotestosterone were measured in normal and hypertrophic tissue and were found to be essentially the same. These observations suggest that dihydrotestosterone accumulation may be causally linked to the development of canine prostatic hypertrophy. However, the mechanism by which dihydrotestosterone accumulates in the prostate remains to be determined.