Concentrations Of Cyproterone Acetate Research Articles

Nonylphenol and cyproterone acetate effects in the liver and gonads of Lithobates catesbeianus (Anura) tadpoles and juveniles.

Environmental pollution plays an important role in amphibian population decline. Contamination with endocrine disrupting chemicals (EDCs) is particularly worrying due to their capacity to adversely affect organisms at low doses. We hypothesized that exposure to EDCs such as 4-nonylphenol (NP) and cyproterone acetate (CPA) could trigger responses in the liver and gonads, due to toxic and endocrine disrupting effects. Growth rate may also be impaired by contamination. We investigated sublethal effects of a 28-day exposure to three different concentrations of NP and CPA on liver pigmentation, gonadal morphology, body mass, and length of tadpoles and juveniles Lithobates catesbeianus. Liver pigmentation and the gonadal morphologies of treated tadpoles did not differ from control, but growth rate was impaired by both pollutants. Juveniles treated with 10 μg/L NP and 0.025 and 0.25 ng/L CPA displayed increased liver melanin pigmentation, but gonadal morphologies, sex ratios, and body mass were not affected after treatments. The increase in liver pigmentation may be related to defensive, cytoprotective role of melanomacrophages. The decreased growth rate in tadpoles indicates toxic effects of NP and CPA. Thus, contamination with NP and CPA remains a concern and sublethal effects of different dosages of the compounds on native species should be determined.

Genotoxic effects of 4-nonylphenol and Cyproterone Acetate on Rana catesbeiana (anura) tadpoles and juveniles

Genotoxic analyses are commonly used in ecotoxicological studies as early biomarkers to investigate the potential effects of environmental contaminants on biological models. Several pollutants can induce DNA damage and, therefore, counting micronuclei and other nuclear abnormalities are efficient tools to evaluate genotoxicity. Some pollutants such as 4-nonylphenol (NP), a detergent used mainly in industries, and Cyproterone Acetate (CPA), an antiandrogenic medicine, have already shown genotoxic effects on some vertebrates. However, although amphibians are considered bioindicators of environmental quality and their populations are declining worldwide, the effects of these compounds on anurans are not yet known and, therefore, we believe that it is important to investigate such effects on anurans. Since water contamination is one of the ultimate causes of amphibian decline, ecotoxicological studies are important to discuss the appropriate solutions to avoid species extinction. Thus, this study investigates the genotoxic effects on Rana catesbeiana tadpoles and juveniles after being exposed to 1, 10 and 100 μg/L NP and 0.025, 0.25 and 2.5 ng/L CPA, by counting the nuclear abnormalities after exposure. The laboratory experiments lasted 28 days. The experimental conditions were the same except for the water volume since tadpoles and juveniles exhibit different habits at different developmental stages. Compared to juveniles, tadpoles were more susceptible to both compounds as indicated by the increased nuclear abnormalities observed in the highest NP concentration and all tested CPA concentrations. The juveniles, on the other hand, responded only to the two highest CPA concentrations. We concluded that CPA, even at very low concentrations, is extremely harmful to both anuran developmental stages and, particularly, to tadpoles. The significant effects observed on tadpoles is an important outcome of this study since 100 μg/L or higher NP concentrations are frequently detected in the environment.

Impacts of an Anti-Androgen and an Androgen/Anti-Androgen Mixture on the Metabolite Profile of Male Fathead Minnow Urine

Male and female fathead minnows (Pimephales promelas, FHM) were exposed via water to 20 or 200 microg/L of cyproterone acetate (CA), a model androgen receptor (AR) antagonist. FHM were also exposed to 500 ng/L of 17beta-trenbolone (TB), a model AR agonist, and to mixtures of TB with both concentrations of CA. The urine metabolite profile (as measured by 1H NMR spectroscopy) of male FHM exposed to the high concentration of CA was markedly different from that of controls, and this difference was less for males coexposed to the associated TB+CA mixture. The exposure to TB alone had almost no impact on the male urine profile. These results suggest that male FHM urinary metabolite profiling may be useful for directly detecting effects of anti-androgens. In contrast, the urinary profile of male FHM exposed to the lower concentration of CA was not very different from that of controls, but, unexpectedly, this difference was increased when coexposed to the associated TB+CA mixture. This suggests that TB with CA at the lower concentration impacts male FHM through an interactive effect possibly unrelated, or in addition, to AR antagonism. The relative occurrence of male-like nuptial tubercles in female FHM exposed to TB and to the mixtures of TB and CA supported the metabolomics data.

Effects of a model androgen (methyl testosterone) and a model anti-androgen (cyproterone acetate) on reproductive endocrine endpoints in a short-term adult mummichog ( Fundulus heteroclitus) bioassay

A short-term gonadal recrudescence bioassay using the mummichog ( Fundulus heteroclitus) was employed to examine the consequences of environmentally relevant and pharmacological exposures (1–1000 ng/l) of the androgen, 17α-methyl testosterone (MT), and the anti-androgen, cyproterone acetate (CA), on reproductive endocrine endpoints. Recrudescing male (GSI=approx. 2%) and female (GSI=approx. 10%) fish were exposed to graded concentrations of MT and CA for 7 or 14 days. In the first experiment (7-day exposure), MT concentrations of 250 or 1000 ng/l decreased circulating testosterone (T) and estradiol (E 2) in female fish, and 11-ketotestosterone (11-KT) in male fish. Plasma T, 11-KT and E 2 were decreased following CA exposure (250 and 1000 ng/l). Gonadal steroid biosynthetic capacity was also inhibited in both sexes after exposure to MT or CA, as evidenced by decreased in vitro production of T and E 2. In experiment 2 (14-day exposure), exposures to lower MT and CA concentrations (1, 10 and 100 ng/l) resulted in decreased plasma T, with females showing greater sensitivity than males. Both 11-KT and E 2 were significantly reduced beginning at 10 ng/l MT. In vitro gonadal T production was impaired at 100 ng/l MT in both males and females while 1 ng/l CA caused a significant decrease in female fish. In experiment 2, in vitro E 2 production was decreased in females at all concentrations of MT and CA, while only 100 ng/l reduced 11-KT synthesis in males. Plasma vitellogenin (Vtg) was reduced in females exposed to 1000 ng/l (experiment 1) and 100 ng/l (experiment 2) MT, while CA did not alter plasma Vtg at any concentration. This bioassay has the potential to be used to assess the possible consequences in estuarine fish of exposure to environmental anti/androgens.

Simultaneous spectrophotometric determination of cyproterone acetate and estradiol valerate in pharmaceutical preparations by ratio spectra derivative and chemometric methods

Ratio spectra derivative spectrophotometry and two chemometric methods (classical least squares, CLS and inverse least squares, ILS, were proposed for the simultaneous quantitative analysis of a binary mixture consists of cyproterone acetate (CA) and estradiol valerate (EV) in the commercial pharmaceutical preparations. In the ratio spectra derivative method, linear regression equations for both drugs were obtained by measuring the analytical signals at the wavelenghts corresponding to either maximums and minimums in the first derivative spectra of the ratio spectra. In the chemometric techniques, the concentration matrix was prepared by using the synthetic mixtures containing these drugs. The absorbance matrix corresponding to the concentration matrix was obtained by measuring the absorbances at 14 wavelengths in the range 220–290 nm for the zero-order spectra. Two chemometric calibrations were constructed by using the absorbance matrix and concentration matrix for the prediction of the unknown concentrations of CA and EV in their mixture. The numerical values were calculated by using ‘ maple v’ software. The accuracy and the precision of the methods have been determined and they have been validated by analyzing synthetic mixtures containing these two drugs. The proposed methods were successfully applied to a pharmaceutical formulation, sugar-coated tablet, and the results were compared with each other.

Evidence that chlormadinone acetate exhibits antiandrogenic activity in androgen-dependent cell line

Chlormadinone acetate (CMA), like other 17-hydroxyprogesterone derivatives, is thought to be a potential antiandrogen on the basis of its effect on spontaneous benign prostatic hyperplasia (BPH) in dogs. This work was undertaken to find out whether CMA presents antiandrogen activity in human androgen-dependent cell line. For this purpose, we used PALM cells, the PC-3 cell line stably transfected with human androgen receptor and a luciferase gene under transcriptional control of MMTV. Potential antiandrogenic activity was compared with that of cyproterone acetate (CPA), a standard steroidal antiandrogen. Both compounds were tested in competitive binding assays at 37 °C in the presence of 1 nM of [ 3H] R1881, a synthetic and non-metabolizable androgen. Their impact on AR transcriptional activity was evaluated by the measure of luciferase activity in the presence of R1881 with increasing concentrations of CMA or CPA (10 −8–10 −6 M). In whole cell binding assays, competitive studies revealed that the Ki for CMA was 3.3±1.5×10 −8 M (versus 7.2±1.3×10 −8 M for CPA). Inhibition of AR transcriptional activity was 40±5% for CMA (3×10 −7 M) versus 59±6% for CPA at the same concentration. Moreover, CMA caused a slower import of green fluorescent protein (GFP)-AR to the nuclei of COS-7 cells than R1881. These data show that CMA exerted a competitive binding for AR and significantly decreased the AR transcriptional activity. In conclusion, this synthetic progestin presents simultaneous antiandrogenic activity that could be helpful as a new therapeutic option in women with luteal defect along with clinical signs of hyperandrogenism.

Cyproterone acetate induces a cellular tolerance to cadmium in rat liver epithelial cells involving reduced cadmium accumulation

Several reports indicate that some steroids, in particular sex steroid hormones, can modify cadmium toxicity. We recently reported that cyproterone acetate (CA), a synthetic steroidal antiandrogen that is closely related in structure to progesterone, affects cadmium toxicity in mice. In the present study, we investigated the effect of CA on cadmium toxicity in a rat liver epithelial cell line (TRL 1215) in vitro. Cells were exposed to various concentrations of CA (0, 1, 10, or 50 μM) for 24 h and subsequently exposed to cadmium (0, 50, or 100 μM; as CdCl 2) for an additional 24 h. CA pretreatment resulted in a clear decrease in the sensitivity to cadmium. Additional time course study showed CA pretreatment provided protection against cadmium toxicity but only when given for 6 or more hours prior to cadmium exposure. Cellular cadmium accumulation was markedly reduced (60% decrease) in cells pretreated for 6 or more hours with CA. In the presence of protein synthesis inhibitors the protective effect of CA toward cadmium toxicity was abolished. However, in the presence of the GSH synthesis inhibitor, l-buthionine (S,R)-sulfoximide (BSO), the protective effect of CA toward cadmium toxicity remained. CA alone increased metallothionein (MT) levels 2.4-fold, while cadmium (50 μM) alone resulted in a 8.9-fold increase over control. However, cadmium-induced MT synthesis was markedly decreased by CA pretreatment probably because of reduced cadmium accumulation. Analysis of various metal transporters by bDNA signal amplification assay revealed that the ZnT-1 transporter gene, which encodes for a membrane protein associated with zinc efflux, was expressed three-fold more in CA treated cells than control. These data show that CA pretreatment provides protection against cadmium toxicity in vitro and indicate that this protection is due to a decreased accumulation of cadmium rather than through activation of MT synthesis. This decrease of cellular cadmium accumulation appears to be related to events that require protein synthesis and may be due to activation of the genes associated with zinc efflux.

Effects of insulin, glucagon and triiodothyronine on DNA synthesis in rat hepatocyte primary cultures induced by liver tumour promoters and EGF

Enhanced cell proliferation may favour DNA-damaging processes (tumour initiation) as well as the expansion of clones of altered cells (tumour promotion). The latter process appears to be responsible for carcinogenesis by non-genotoxic compounds. We previously have established rat hepatocyte primary cultures under serum-free conditions and studied the effect of the rat liver tumour promoter cyproterone acetate (CPA) on DNA synthesis. It was found that glucocorticoid concentration of 100 n m dexamethasone was necessary for the induction of DNA synthesis. In the present study the growth supporting effect of insulin, glucagon and triiodothyronine (T3) were examined. Pretested concentrations of CPA, pregnenolone-16α-carbonitrile (PCN), α-hexachlorocyclohexane (HCH), nafenopin (NAF) and phenobarbital (PB) were added for stimulation of DNA synthesis. EGF served as a reference stimulator. Beginning with standard medium concentrations of insulin (7 nM), glucagon (0.4 nM) and triiodothyronine (100 nM) dose-response studies were obtained by leaving all but one of the hormone concentrations constant. DNA synthesis was measured by incorporation of [ 3H]thymidine into DNA. In solvent-treated dimethyl sulfoxide (DMSO) cultures insulin at 6 nM and higher induced a 2.5-fold induction of DNA synthesis. Insulin also enhanced DNA synthesis induced by CPA, HCH, NAF, PCN and EGF but not by phenobarbital (EC 50, 2–3 n m). The effect of glucagon (0.016n m–16n m) appeared to be much less prominent and was observed only at superphysiological concentrations with CPA, PCN, HCH and EGF. DNA synthesis induced by NAF was slightly suppressed at 1.6n m glucagon. T3 did not induce DNA synthesis by itself, nor was there modulation of DNA synthesis induced by rat liver tumour promoters. Thus the so-called hepatotrophic hormones differentially modulate the induction of DNA synthesis by rat liver tumour promoters in primary rat hepatocyte cultures.

Pharmacokinetics of cyproterone acetate and ethinylestradiol in 15 women who received a combination oral contraceptive during three treatment cycles

The pharmacokinetics of cyproterone acetate (CPA) and ethinylestradiol (EE 2) were determined in 15 healthy women (age 19 to 34 years), following single dose administration of a combination oral contraceptive, containing 2.0 mg CPA together with 0.035 mg EE 2 (Dia-ne-35 R). After a wash-out period of one week, the same preparation was administered during a treatment period of three months. After single dose administration, maximum concentrations of CPA in the serum were 15.2 ± 6.6 ng/ml. Post maximum drug levels declined biphasically with half-lives of 0.8 ± 0.4 h and 54.0 ± 26.0 h, respectively. The apparent clearance was calculated to be 3.6 ± 0.9 ml × min −1 × kg −1 and the volume of distribution (V z) was 986 ± 437 1. The free fraction of CPA was 3.5 ± 1.9% and the fractions bound to heat labile proteins and albumin were 4.6 ± 2.2 % and 92.0 ± 3.5%, respectively. Trough levels of CPA in the serum increased during a treatment cycle, reaching a steady-state around day 16. An about two-fold accumulation of CPA was observed, which was less than expected theoretically. SHBG concentrations in the serum increased by a factor of three during a cycle, without having any effect on the protein binding of CPA. At the end of treatment cycle three, the terminal half-life of CPA had increased to a mean value of 78.6 ± 16.0 h and the volume of distribution to a value of 1304 ± 427 1. The apparent clearance showed a small, although significant decrease to a value of 3.0 ± 0.4 ml × min −1 × kg −1. The observed changes V z and t 1/2 during the treatment period were attributed to the distribution of CPA into a deep compartment and the slow release of the drug from this compartment. The AUC(0–4h) values of EE 2 following single dose administration of the combination oral contraceptive were found to be 187.5 ± 79.7 pg × ml −1 × h. On the last day of cycles one and three, the AUC(0–4h) values were 311.2 ± 109.3 and 304.8 ± 121.5 pg × ml −1 × h, respectively, which corresponds to an about 60% increase as compared to single dose administration. Total and free testosterone concentrations decreased during treatment cycles one and three by about 39 % and 62%, respectively, compared with the corresponding values measured prior to treatment.

Androgens and androgen-receptors in prostate tissue from patients with benign prostatic hyperplasia: Effects of cyproterone acetate

Testosterone, 5α-dihydrotestosterone and cyproterone acetate (CPA)_were estimated in samples of prostate tissue, obtained from benign prostatic hyperplasia (BPH) patients who were or were not pretreated with CPA. Furthermore, these steroids were estimated in various fractions of the BPH tissue, and the number of nuclear androgen-receptor sites was determined. CPA-treatment caused a 4-fold, significant suppression of 5α-dihydrotestosterone levels in total prostate tissue and its subfractions, without affecting testosterone levels or the androgen-receptor contents of the nuclear extracts. Nuclear concentrations of CPA were twice as high as those of 5α-dihydrotestosterone. It is conclude that effects of CPA may have been caused through a combination of the following mechanisms: (1) suppression of peripheral androgen levels: (2) competition with androgens for (nuclear) androgen-receptors; and (3) suppression of prostatic 5α-reductase.

Induction by cyproterone acetate of DNA synthesis and mitosis in primary cultures of adult rat hepatocytes in serum free medium

The aim of this study was to elucidate whether serum-free conditions could be found in primary hepatocyte cultures under which the growth inducing properties of xenobiotics and hormones could be tested. Cyproterone acetate (CPA), a steroid with anti-androgenic and progestogenic activity, was chosen as a model compound because of its known strong mitogenic properties in rat liver in vivo. EGF served as a positive control. Induction of DNA synthesis was studied by [3H]-thymidine labeling and autoradiography. Mitoses were counted in hematoxylin stained specimens. The main steps which led to an efficient stimulation of DNA synthesis by CPA were (i) reduction of hormone concentrations to levels approaching (approx. 10x) physiological concentrations better than the previously used pharmacological ones (up to 2500x); (ii) supplementation with glucocorticoid (most effective at 10-100 nM dexamethasone); (iii) selection of the interval for cumulative labeling with thymidine at 44-68 h; (iv) lowering of cell density at seeding to 50,000 cells/cm2 (subconfluency); (v) treatment with concentrations of 10-100 microM CPA. With these conditions CPA labelling was 13-20% (increase 4- to 9-fold). Mitotic incidence was 0.56% (CPA) versus 0.08% in controls. From a dose response study (0.1-100 microM) a no-effect-level for induction of DNA synthesis was found in the range of 0.1-1 microM. None of the high concentrations of CPA did cause cytotoxicity as estimated by morphological observations or release of lactate dehydrogenase into the medium. This work demonstrates that CPA under appropriate, defined culture conditions induces DNA synthesis and mitosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and endocrine effects of cyproterone acetate in postmenopausal patients with advanced breast cancer

A phase II study with cyproterone acetate (CPA) was done as the primary treatment in female breast cancer patients. Twenty-three patients, mean age 64 years, range 52–75 years, were entered and treated with CPA 400 mg daily. Twenty patients were evaluable and responses were sparse. There was one partial and one complete remission, 17 patients were stable and one patient progressed within 3 months. Side-effects were frequent: five patients complained of nausea, three had severe weight loss, one suffered from depression and seven showed disturbed liver function tests. Six patients had to stop treatment for side-effects, while two other patients were taken off treatment because they developed an acute necrotizing hepatitis. The hepatitis recovered after drug withdrawal in both patients. The serum levels of CPA, cortisol, androstenedione, DHAS, LH, FSH and prolactin were measured during CPA treatment. The levels of cortisol and androstenedione did not change, while LH, FSH and DHAS were suppressed. The DHAS showed an inverse relation to serum CPA concentrations. The prolactin levels rose uniformly. The therapeutic effect of CPA in postmenopausal patients with advanced breast cancer is disappointing, and inferior to that of other progestins. Side-effects are frequent, possibly as a result of the high dosage used in this study. The hormonal changes are different from those of other progestins, which may explain the different efficacies.

A reversed-phase high-performance liquid chromatographic method for the simultaneous determination of serum concentrations of cyproterone acetate and 15 beta-hydroxycyproterone acetate.

A reversed-phase high-performance liquid chromatographic method for the simultaneous determination of cyproterone acetate (CPA), 15 beta-hydroxycyproterone acetate (15 beta-OH-CPA) and cyproterone (CP) was reported. This method was specific, sensitive, precise, easy and rapid for determination of the serum concentrations of these steroids in patients receiving CPA. Although no peak corresponding to CP was observed for serum, peaks corresponding to CPA and 15 beta-OH-CPA were detected and well separated in all subjects undergoing long-term CPA therapy. In these patients, there seemed to be a dose-dependent relationship between the amount of CPA administered and the serum concentrations of these steroids, and the serum concentrations of CPA were either similar or low compared with those of 15 beta-OH-CPA. In conclusion, this simplified method is thought to be very valuable for studies on the pharmacokinetics of CPA and 15 beta-OH-CPA, and on the relationship between the CPA dosage and the therapeutic or side effects on adrenal and gonadal steroid production.

On the site of action of the anti-adrenal steroidogenic effect of cyproterone acetate

Cyproterone acetate (CA) inhibited 1–24 ACTH (50 ng/l)-stimulated cortisol production by dispersed guinea-pig adrenal cells in a dose-related manner. Inhibition occurred over the range 10 −6 to 5 × 10 −5 moles/l. The concentration of drug which induced 50% inhibition was 4.6 × 10 −6 moles/l. The sites of action of this anti-steroidogenic effect have been established. Dispersed adrenal cells were challenged with the cortisol precursor steroids (all at 10 −5 moles/l) pregnenolone (Pe), 17 α hydroxy- pregnenolone (17-OH Pe), 17 α-hydroxyprogesterone (17-Po), and 11 deoxycortisol or 1–24 ACTH (100 ng/l) in the absence and presence of increasing concentrations of CA (10 −5 to 10 −4 moles/l). In the absence of drug, the steroid precursors or ACTH provoked cortisol secretion greater than 10-fold that secreted by cells incubated in their absence. ACTH-stimulated cortisol secretion was inhibited >68% at concentrations of CA >10 −5 moles/l. CA (10 −5 moles/l) had no significant effect on steroidstimulated cortisol production when the Δ 4, 3 ketosteroids 17-OH Po and 11-deoxycortisol were used, but depressed secretion by >61% (P < 0.001) when the Δ 5 3 β hydroxysteroids (Pe, 17-OH Pe) were employed. Increasing CA concentrations to 10 −4 moles/l had little effect on cortisol secretion provoked by 11-deoxycortisol, but significantly (P < 0.05) depressed cortisol secretion stimulated by 17-OH Po. These results suggest that the major site of action of CA is Δ 5, 3β hydroxysteroid dehydrogenase (3β- HSD) with a secondary effect on 21-hydroxylase activity. To confirm these findings cortisol secretion provoked by 17, 21, dihydroxypregnenolone (17, 21 diOH Pe) and 21 deoxycortisol (21-DOC) was measured in the absence and presence of increasing concentrations of CA. At the lowest concentration of CA (5 × 10 −6 moles/l), cortisol secretion provoked by 17, 21 diOH Pe was inhibited by 28% (P < 0.01) whereas secretion provoked by 21-DOC was not significantly affected. At the highest concentration of CA (10 −4 moles/l), the relative inhibition was 80% for 17, 21 diOH Pe and 38% for 21-DOC. We conclude that cyproterone acetate inhibits adrenal steroidogenesis at both 3β-HSD and 21- hydroxylase, the degree of inhibition being more pronounced at 3β-HSD.

Cyproterone acetate, testosterone, LH, FSH, and prolactin levels in plasma after intramuscular application of cyproterone acetate in patients with prostatic cancer.

Five patients with prostatic carcinoma (stages T3N0M0) were injected intramuscularly with 300 mg of cyproterone acetate (CPA) (Androcur-Depot) at weekly intervals. The concentrations of CPA, testosterone, LH, FSH, and prolactin in plasma after the first, third, and fifth injection were measured by specific radioimmunoassays. After five injections of Androcur-Depot, CPA levels were slightly higher than in previous determinations, suggesting that a balance between active substance release from the depot and excretion could be achieved after eight to twelve injections, with only slightly higher levels of active substance attained. Testosterone levels clearly were reduced after the first injection of CPA, but the lowest values were registered only after three injections. Plasma concentrations of FSH and LH were slightly diminished, whereas the prolactin level increased after CPA therapy.

Adrenal and Ovarian Steroids versus Cyproterone Acetate(CA) in Girls with Precocious Puberty(PP)

Serum concentrations of testosterone(T), Δ4-androstenedione(A), dehydroepiandrosterone(DHEA) and its sulfate(DS), estradiol(E2), cortisol(F), and CA vere measured by radloimmunoassays repeatedly in 11 girls with PP, treated vith 81-136 mg/M2/d of CA for 2-60 ttonths(Tatle indicates ranges). Hormones were also determined 30' after 0.25mg of tetracosactid i.v.DHEA and A increased in 7/11 and 8/11, T in 2/11, DS in none. There vas no relation to the response of F(normal in 4, subnormal in 3, absent in 4)or to the CA levels. Thus high-dose CA treatment suppressed E2 and adrenal steroids, T remained elevated in half of the girls with high CA concentrations. possibly related to its anti-androgen effect.

Evaluation of the use of cyproterone acetate competition to distinguish between high-affinity binding of [ 3H]-dihydrotestosterone to human prostate cytosol receptors and to sex hormone-binding globulin

From preliminary experiments, it was concluded that cyproterone acetate (CA) was the most satisfactory of several anti-androgens investigated in distinguishing between high-affinity binding of [ 3H]-5α-dihydrotestosterone to rat ventral prostate cytosol and to human serum, using a simple incubation technique followed by removal of free steroid by Dextran-coated charcoal. Rat prostate cytosol (androgen receptor) binding of [ 3H]-DHT was almost eliminated by concentrations of CA which affected human serum binding to a relatively slight, though unfortunately variable, extent. The total, high-affinity, and CA-inhibitable binding of [ 3H]-DHT by prostatic cytosol of a number of patients with benign prostatic hypertrophy and prostatic carcinoma was investigated. In the untreated patients and in some patients treated by orchidectomy and/or estrogens, the total and CA-inhibitable high affinity binding of [ 3H]-DHT were correlated with the endocrine status of the patient as determined by the serum testosterone level and the high affinity [ 3H]-DHT binding capacity of the serum (equivalent to sex-hormone binding globulin (SHBG)). It was concluded that the use of cyproterone acetate to distinguish between [ 3H]-DHT binding to the androgen receptor and serum components in human prostate cytosol permits a semi-quantitative evaluation of the amounts of these two components.