cyproterone and Prostatic-Hyperplasia

Antiandrogens, substances that prevent androgens from expressing their activity at target cells, play an important role in the treatment of prostate cancer. The most frequently used substances have either a steroidal structure (cyproterone acetate) or a non-steroidal structure (Flutamide or Anandron). Antiandrogens have been tested both alone and in combination with treatments aimed at inhibiting testicular secretion (castration, LH-RH analogs), thereby producing complete blockade of androgen secretion and action. Patients treated by such combination protocols have often shown an improvement in the percentage of remissions and, less often, improvement in survival. Administration of antiandrogens improves the clinical symptoms of patients with benign prostatic hypertrophy, but the exact mechanism of their action requires further investigation. Cutaneous manifestations due to hyperandrogenicity (hirsutism, alopecia, acne) have also been improved by cyproterone acetate, which is often given together with estrogens (reversed sequential regime), by spironolactone or topically applied products. Finally, antiandrogens have been successfully used to treat breast cancer in men, early puberty, hypersexuality and sexual deviations.

Topics: Androgen Antagonists; Breast Neoplasms; Cyproterone; Cyproterone Acetate; Female; Flutamide; Humans; Imidazoles; Imidazolidines; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Puberty, Precocious; Skin Diseases; Spironolactone

Topics: Adrenergic alpha-Antagonists; Bromocriptine; Cyproterone; Gestonorone Caproate; Humans; Male; Medrogestone; Megestrol; Plant Extracts; Polyenes; Prostatic Hyperplasia; Spironolactone; Tamoxifen

Topics: Acne Vulgaris; Alopecia; Animals; Bone Development; Cyproterone; Female; Fertility; Hirsutism; Humans; Libido; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Puberty; Sebaceous Glands; Seminal Vesicles; Sex Differentiation; Skin; Testis

Many antiandrogens, mainly steroidal and some nonsteroidal agents, have been synthesized and tested in several available biological assays. Unfortunately, many of these compounds have other biological activities which make it difficult to ascertain the precise mechanism of antiandrogenic action. The blocking of androgen action can be accomplished by a number of ways: (1) the inhibition of gonadotropin release and/or synthesis, (2) the interference with testosterone and/or dihydrotestosterone biosynthesis, (3) the blocking of protein synthesis, and (4) the competition with androgens at receptor sites. Although the major reason for the development of antiandrogens is to utilize them in certain clinical situations, some have become important tools in studying androgen action, particularly on the molecular level. The clinical effectiveness of some antiandrogens in prostatic hyperplasias, hirsutism, and acne represents an important advance in therapeutics, but the search for more potent antiandrogens with minimal side effects should continue.

Topics: Acne Vulgaris; Androgen Antagonists; Animals; Biological Assay; Comb and Wattles; Cyproterone; Female; Fertility; Flutamide; Genitalia, Male; Hirsutism; Male; Phthalimides; Progesterone; Prostatic Hyperplasia; Prostatic Neoplasms; Sebaceous Glands; Sebum; Sex Differentiation; Sexual Behavior, Animal; Sexual Dysfunction, Physiological; Steroids

Topics: Adult; Aged; Aging; Androgens; Androstane-3,17-diol; Androstanes; Androstenedione; Androsterone; Animals; Blood Proteins; Cyproterone; Dihydrotestosterone; Estradiol; Estrogens; Female; Humans; Male; Middle Aged; Muscles; Progestins; Prostate; Prostatic Hyperplasia; Protein Binding; Testosterone

Topics: Androgen Antagonists; Androgens; Animals; Castration; Cyproterone; Dogs; Drug Synergism; Estrogens; Hormones; Humans; Male; Medrogestone; Middle Aged; Polyenes; Progestins; Prostate; Prostatic Hyperplasia; Species Specificity; Spironolactone

Topics: Carcinoma; Cyproterone; Female; Hirsutism; Humans; Male; Paraphilic Disorders; Prostatic Hyperplasia; Prostatic Neoplasms; Puberty, Precocious; Sex Offenses

Topics: Adenocarcinoma; Age Factors; Aged; Cyclophosphamide; Cyproterone; Diethylstilbestrol; Fluorouracil; Humans; Male; Neoplasm Metastasis; Nitrogen Mustard Compounds; Prognosis; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms; Urination

The possible effect of medical androgen deprivation in the treatment of benign prostatic hyperplasia has been studied in 12 patients. Six patients received the luteinizing hormone-releasing hormone agonist buserelin and 6 others received the antiandrogen cyproterone acetate. The treatment resulted in an average decrease in prostatic size of 29 per cent after 12 weeks as measured by ultrasonography. This decrease led to an increase in peak urinary flow rate, a reduction in residual urine volume and a decrease in daytime voiding frequency. However, it caused no decrease in urethral resistance but only an increase in the bladder contraction strength. After discontinuation of the treatment the prostates showed regrowth to the initial sizes within 6 to 36 weeks. The urodynamic changes were reversed as well. Although statistically significant, the urodynamic changes were minimal from a clinical viewpoint and did not lead to an unobstructed state after 12 weeks of treatment. For this reason the clinical indication for use of medical androgen deprivation in benign prostatic hyperplasia patients will remain limited for the time being.

Topics: Androgen Antagonists; Buserelin; Cyproterone; Cyproterone Acetate; Humans; Male; Prospective Studies; Prostate; Prostatic Hyperplasia; Random Allocation; Ultrasonography; Urodynamics

In order to evaluate the biochemical modifications induced by hormonal treatments on human prostatic tissue, the intracellular distribution of tissue DHT and AR were investigated in BPH patients untreated and treated (25-30 days before surgery) with the association of cyproterone acetate (CPA), 100 mg p.o./day plus tamoxifen (TAM), 100 mg p.o./day, or with flutamide (FLU) alone, 750 mg p.o./day. Dextran-coated charcoal and exchange assay in the presence of sodium molybdates (0.2 M) were used for AR determination, employing methyltrienolone as radioligand in the presence of triamcinolone acetonide. Endogenous DHT was measured by RIA, after ether extraction and purification on celite microcolumns. The treatment with CPA plus TAM led to a detection of cytosol AR (ARc) in 50% of the specimens, while nuclear AR (ARn) were never measurable. The FLU treatment did not modify the incidence of ARc, while ARn was not detectable. The cytosolic and nuclear compartmentalization of DHT was scarcely affected by the combined CPA plus TAM treatment, while FLU treatment induced a prevalent cytosolic localization of DHT (DHTc = 283.2 +/- 24.6 S.E. and DHTn = 1138.4 +/- 98.7 S.E. pg/mg DNA in untreated patients; DHTc = 350.4 +/- 97.7 S.E. and DHTn = 589.7 +/- 154.4 S.E. pg/mg DNA in CPA plus TAM treated patients; DHTc = 1101.7 +/- 165.7 S.E. and DHTn = 733.0 +/- 93.9 S.E. pg/mg DNA in FLU treated patients). Both medical treatments, therefore, were able to reduce prostatic growth on account of the reduced value of nuclear DHT content.

Topics: Androgen Antagonists; Anilides; Cell Nucleus; Cyproterone; Cyproterone Acetate; Cytosol; Dihydrotestosterone; Flutamide; Humans; Male; Prostate; Prostatic Hyperplasia; Receptors, Androgen; Tamoxifen

Topics: Adult; Aged; Androgen Antagonists; Bromocriptine; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Humans; Male; Middle Aged; Prostatectomy; Prostatic Hyperplasia

18 patients with obstructive benign prostatic hypertrophy were studied. A 5-day treatment with gestonorone caproate (200 mg daily and 200 mg on alternate days) and cyproterone acetate (300 mg daily) suppressed the plasma LH and serum LH levels. Subsequently, H3-testosterone was injected intravenously and its elimination from plasma and uptake and metabolism in the BPH tissue studied. The elimination of total radioactivity and H3-testosterone from plasma was not altered after the 3 treatment regimens as compared to the control group. The uptake of total radioactivity into BPH tissue and its intraprostatic metabolism particularly to dihydrotestosterone was significantly suppressed in the patients with daily injections of gestonorone. Cyproterone acetate and gestonorone caproate on alternate days did not cause this effect.

Topics: Aged; Clinical Trials as Topic; Cyproterone; Gestonorone Caproate; Humans; Luteinizing Hormone; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Testosterone

Mongolian gerbils (Meriones unguiculatus) were grouped into two experimental groups: GEx.01 suffered orchiectomy and after 30 days received doses of testosterone cipionate (T), while GEx.02 received weekly and alternated doses of the anti-androgens cyproterone acetate and flutamide for 30 days, and the animals were then euthanized. Structural evaluation reveals a more intense reduction in epithelial height in GEx.02. Smooth muscle cells (SMC) presented a star-shaped aspect after 30 days of hormonal ablation and basal membrane was shown to be more intensely grooved in GEx.01. In both groups, after hormonal replacement, recovery in epithelial height could be noted and the SMC presented its phenotypes, but an increase in RER was seen, characterizing a modulation from its contractile to secreting phenotype. In conclusion, the prostate presented involution capacity after androgen ablation and the ability to reorganize after hormonal replacement, but events resulting from orchiectomy and subsequent T replacement were shown to be more aggressive to the prostate.

Topics: Acid Phosphatase; Androgen Antagonists; Animals; Cyproterone; Disease Models, Animal; Endoplasmic Reticulum, Rough; Endothelium; Flutamide; Gerbillinae; Immunohistochemistry; Male; Microscopy, Electron, Transmission; Orchiectomy; Organ Size; Prostate; Prostatic Hyperplasia; Protein Tyrosine Phosphatases; Receptors, Androgen; Testosterone

Testosterone, 5 alpha-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 5 alpha-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 5 alpha-dihydrotestosterone. It is concluded 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 5 alpha-reductase.

Topics: 5-alpha Reductase Inhibitors; Androgens; Binding, Competitive; Cell Nucleus; Cyproterone; Cyproterone Acetate; Dihydrotestosterone; Humans; Male; Prostate; Prostatic Hyperplasia; Receptors, Androgen; Testosterone

Local hyperthermia to the prostate has initially been found to be of considerable beneficial value in cancer of the gland and later also in benign prostatic hypertrophy (BPH) and in chronic prostatitis. The Prostathermer has been especially developed and used for this purpose. 124 patients with BPH, who have been treated by this method, were reevaluated after 1 year. This thermotherapy was well tolerated, and no noticeable complications were encountered. A sustained definite improvement in objective and subjective obstructive symptoms and signs was seen in 51% of the cases. Such definite and persistent improvement was best obtained when treatments were performed twice weekly for 60 min over a period of 3 weeks. Those patients with the more severe obstructive symptoms fared best. A full explanation for the effectiveness of this treatment of BPH has yet to be found. Although local hyperthermia cannot, at this stage, be considered as a radical form of treatment of BPH, it may offer definite relief to about 50% of the cases, particularly to those unwilling or unsuitable for surgery.

Topics: Androgen Antagonists; Cyproterone; Cyproterone Acetate; Follow-Up Studies; Humans; Hyperthermia, Induced; Male; Prostatic Hyperplasia; Time Factors; Urination; Urine; Urodynamics

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents; Catheters, Indwelling; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Humans; Hyperthermia, Induced; Male; Microwaves; Middle Aged; Prostatic Hyperplasia; Time Factors; Urinary Bladder Neck Obstruction; Urinary Catheterization; Urination

Interference with estrogenic and androgenic actions might result in an inhibitory effect of benign prostatic hyperplasia (BPH). In the present study the effects of the treatment of intact, adult beagle dogs with the antiandrogen cyproterone acetate (CPA) and the aromatase inhibitor 1-methyl-ADD either alone or in combination on androstenedione-induced prostate growth and on testes, epididymides, and the pituitary was investigated. 1-Methyl-ADD induced a marked counterregulatory increase in the serum testosterone and dihydrotestosterone (DHT) concentrations leading to hyperplasia of the glandular part of the prostate. However, the aromatase inhibitor antagonized the androstenedione-induced (estrogen-related) stimulation of the fibromuscular stroma of the prostate. CPA caused a complete atrophy of the prostate that was also present after treatment with both the aromatase inhibitor and CPA in spite of a striking elevation of the serum testosterone and DHT levels and in spite of the antagonization of the inhibition of testes and epididymal weight induced by androstenedione plus CPA. This indicates a selective inhibition of the prostate of intact beagle dogs treated with CPA and 1-methyl-ADD.

Topics: Androgen Antagonists; Androstenedione; Animals; Aromatase Inhibitors; Cyproterone; Cyproterone Acetate; Dogs; Epididymis; Luteinizing Hormone; Male; Organ Size; Prostate; Prostatic Hyperplasia; Radioimmunoassay; Testis

We examined whether the induction of estrogen-related hyperplastic changes in the prostate (ie, activation and stimulation of the stroma, especially of the smooth muscle) of castrated beagle dogs was reproducible. The effectiveness of the aromatase inhibitor 1-methyl-androsta-1, 4-diene-3, 17-dione (1-Methyl-ADD) in antagonizing such estrogen-related alterations was investigated in comparison with a combined treatment of 1-Methyl-ADD and the antiandrogen CPA. These studies have demonstrated the suitability of the androstenedione model for testing the efficacy of aromatase inhibitors. In addition, it has been demonstrated that an aromatase inhibitor in combination with an antiandrogen can synergically inhibit the glandular and stromal components of the prostate.

Topics: Androstenedione; Animals; Aromatase Inhibitors; Castration; Cyproterone; Cyproterone Acetate; Dogs; Drug Synergism; Drug Therapy, Combination; Male; Prostate; Prostatic Hyperplasia; Time Factors

The antiandrogen cyproterone acetate (CA), as well as oestrogens have been reported to influence pituitary-adrenal function in prostate cancer patients, but the clinical relevance of these findings is unknown. We therefore investigated serum cortisol (F), dehydro-epiandrosterone sulphate (DS), testosterone (T) and prolactin (Prl) levels in patients treated with CA or oestradiol undecylate for at least 6 months. Hypothalamic-pituitary-adrenal function was further assessed by analysis of diurnal hormone variation and by ACTH stimulation and dexamethasone suppression tests. To differentiate between direct CA or oestrogen effects and secondary effects resulting from therapy-induced hypogonadism, we performed similar tests in untreated normogonadal and hypogonadal patients. CA treatment effected a significant decrease in serum F (-40%), DS (-73%) and T (-58%) levels and an increase in serum Prl (+118%). Oestrogen treatment resulted in markedly lowered T levels (-89%), slightly elevated serum F (+24%) and significantly increased serum Prl (+192%). Corresponding changes of F, DS and Prl could not be found in the untreated hypogonadal controls, thus indicating a direct drug-related effect. Neither diurnal rhythmicity of serum F nor adrenal response to ACTH stimulation or sensitivity to dexamethasone suppression significantly changed under CA or oestrogen treatment. We conclude that, although serum F levels may decrease under CA or increase slightly under oestrogen therapy for prostate carcinoma, these findings do not justify specific treatment, since neither clinical side effects nor an impairment of hypothalamic-pituitary-adrenal feedback occurs.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Aged; Circadian Rhythm; Cyproterone; Cyproterone Acetate; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Estradiol; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Prolactin; Prostatic Hyperplasia; Prostatic Neoplasms; Testosterone

The effect of a synthetic steroidal compound TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-estren-3-one) on the binding of methyltrienolone (R1881) and promegestone (R5020) to hyperplastic and neoplastic human prostate was investigated. TSAA-291 inhibits both androgen and progestogen binding to hyperplastic and neoplastic human prostate. Glycerol density gradient analysis revealed that the inhibition of promegestone (R5020) binding by TSAA-291 was significantly greater than that of methyltrienolone (R1881) in both hyperplastic and neoplastic human prostate. The nature of the inhibition was competitive as determined by Scatchard analysis and double reciprocal plots. Comparison of the Ki values for the inhibition by TSAA-291 of R1881 binding (3.2 X 10(-7) M) and of R5020 binding (2.0 X 10(-8) M) suggests that TSAA-291 binds to progesterone receptor with a greater affinity than to androgen receptor. Our results suggest that the effectiveness of the drug in the treatment of benign hyperplasia might be due not only to its anti-androgenic properties but also due to its ability to inhibit progesterone receptor.

Topics: Binding, Competitive; Centrifugation, Density Gradient; Cyproterone; Cyproterone Acetate; Dihydrotestosterone; Estrenes; Humans; Male; Mathematics; Metribolone; Nandrolone; Norpregnadienes; Promegestone; Prostatic Hyperplasia

Topics: Adrenergic alpha-Antagonists; Aged; Aging; Bromocriptine; Cyproterone; Humans; Male; Phenoxybenzamine; Progestins; Prostate; Prostatic Hyperplasia; Spironolactone

The effect of SHBG, stilbestrol and cyproterone acetate on the amount of 3H-DHT in the cell nuclei of hypertrophic prostatic glands was studied in vitro. It was found the SHBG lowers the DHT content, whereas stilbestrol and cyproterone acetate in the presence of SHBG tends to increase the amount of 3H-DHT in the nuclei.

Topics: Adult; Cell Nucleus; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Dihydrotestosterone; Female; Humans; Male; Pregnancy; Prostate; Prostatic Hyperplasia; Sex Hormone-Binding Globulin; Testosterone

Light and electron microscopic measurements show that tissue overgrowth in human benign prostatic hyperplasia is mostly due to an increase in stromal tissue. There is evidence that interaction between stromal and epithelial cells play a critical role in the regulation of the coordinated growth of the prostatic gland. Stromal response to hormones is virtually not completely understood, however at present there are strong indications that it is the androgens above all which control the function of the stromal part of the human prostate. It has been shown that the endogenous concentration of 17 beta-estradiol in the stromal compartment of the guinea pig prostate exceeded that of the blood plasma and prostatic epithelium. In an attempt to shed light on the action of endogeneous androgens and estrogens on the stromal tissue of the human prostate, selective androgen and estrogen antagonists as well as bromocriptine were used to study the stromal reaction pattern in human prostatic hyperplasia.

Topics: Androgen Antagonists; Bromocriptine; Cyproterone; Cyproterone Acetate; Estradiol; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Muscle, Smooth; Prolactin; Prostate; Prostatic Hyperplasia; Tamoxifen; Testosterone

Topics: Aged; Cyproterone; Drug Therapy, Combination; Humans; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Tamoxifen; Ultrasonics

While maintaining the actual conditions prevailing in benign prostatic hyperplasia (BPH) in man, transplantation of BPH tissue to new born rats proved a suitable model for examining the distribution of sexual hormones in different tissue compartments of BPH. In combination with the microautoradiographic method, it was possible to demonstrate the residence of the radio-active androgen 5 alpha-dihydrotestosterone (5 alpha-DHT), the antiandrogen cyproterone acetate (CA) and the oestrogen oestradiol-17 beta (E2) in the epithelium and/or stroma of human BPH tissue. Quantitative evaluation in the form of a point per area count on photographic pictures yielded a silver grain distribution ratio in epithelium and stroma of 1.3: 1 and 1.5: 1 for epithelium to stroma after administration of [3H] 5 alpha-DHT and [3H]CA administration respectively and 0.5: 1 after [3H]E2. The high tracer recovery rate throughout the stroma following E2 administration supports the current view that the stromal proliferation is attributable mainly to oestrogen influences. The relatively high silver particle proportion throughout the stroma following 5 alpha-DHT administration corroborates recent findings which suggest that the exclusive androgen dependency of the glandular epithelium can only be considered in conjunction with an active metabolization of androgens in the stroma. The correspondence in the distribution of the radioactive tracer after [3H] 5 alpha-DHT and [3H]CA administration both in the epithelium and stroma suggest that an antagonism may also exist in the stroma.

Topics: Aged; Animals; Autoradiography; Cyproterone; Cyproterone Acetate; Dihydrotestosterone; Estradiol; Humans; Male; Prostate; Prostatic Hyperplasia; Rats; Rats, Inbred Strains; Silver; Staining and Labeling; Transplantation, Heterologous

We studied the prostates of 22 beagle dogs by light morphometric analysis under defined hormonal influences. Prostatic weight increased with 3 alpha-androstanediol (3 alpha-diol) alone and in combination with 17 beta-estradiol (E2). Two different prostatic hyperplasia models were established. 3 alpha-Diol brings about diffuse glandular prostatic hyperplasia with an absolute increase of glandular parenchyma and, together with E2, provokes stromal hyperplasia with squamous metaplasia of the epithelium and secondary cyst formation. In both models, the antiandrogen cyproterone acetate causes a significant reduction of the absolute and relative volumes of the glandular compartment with antiandrogenic effects on the stroma.

Topics: Androstane-3,17-diol; Androstanols; Animals; Castration; Cyproterone; Disease Models, Animal; Dogs; Estradiol; Male; Metaplasia; Prostate; Prostatic Hyperplasia; Stereoisomerism

In an attempt to shed light on the action of endogenous androgens and estrogens on the stromal tissue of the human prostate, we studied the effect of selective androgen (cyproterone acetate), estrogen (tamoxifen), and prolactin (bromocriptine) antagonists. The application of cyproterone acetate led to a reduced relative volumetric amount of the smooth muscle cell organelles, whereas the administration of tamoxifen effected no alteration as compared to pretreatment values. The administration of bromocriptine led to further activation of the smooth muscle cells in benign prostatic hyperplasia. Hormones, such as leutinizing hormone, follicle stimulating hormone, testosterone, 17-beta-estradiol, and prolactin were measured to assess alterations of the pituitary gonadal axis.

Topics: Aged; Bromocriptine; Cyproterone; Estradiol; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Prolactin; Prostate; Prostatic Hyperplasia; Tamoxifen; Testosterone

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Androstenedione; Biotransformation; Cell Nucleus; Cyproterone; Dihydrotestosterone; Humans; Hydrogen-Ion Concentration; Kinetics; Male; Oxidoreductases; Prostatic Hyperplasia; Proteins

The effect of 3 alpha-androstanediol (3 alpha-diol), 17 beta-estradiol (E2) and cyproterone acetate (CA) on prostates in castrated beagle dogs were investigated by histological and histochemical examinations. A significant increase of prostatic weight occurred after 6 months' treatment with 3 alpha-diol alone and in combination with E2. Histologically and histochemically, two different types of prostatic enlargement were observed: first, administration of 3 alpha-diol resulted in diffuse glandular hyperplasia with replacement of functional activity monitored by strongly positive reactions for acid phosphatase, aminopeptidase and zinc. Second, 3 alpha-diol plus E2 produced stratified squamous metaplasia with cystic lumina and loss of the typical morphological structure. These glands showed negative reactions for acid phosphatase, aminopeptidase and zinc. In both types of prostatic hyperplasia CA abolished epithelial or metaplastic proliferation and induced atrophy of glandular epithelium. In estrogenized dogs activation of the fibromuscular stroma was obvious. CA prevented prostatic hyperplasia by atrophying epithelial effects.

Topics: Acid Phosphatase; Aminopeptidases; Androstanols; Animals; Castration; Cyproterone; Cyproterone Acetate; Disease Models, Animal; Dogs; Estradiol; Male; Prostatic Hyperplasia; Zinc

Cytosol of human benign prostatic hypertrophy bound to R 1881 in a high affinity manner. Most of the protein which bound to R 1881 was recovered in the precipitate of a 0-30% saturation of ammonium sulfate, and was eluted in the void volume on a Sephadex G-200 column. The binding of cytosol to R 1881 was more inhibited by progestins than by dihydrotestosterone and estradiol-17 beta. The binder therefore seemed to be different from dihydrotestosterone-binding protein. The R 1881-binding component extracted from the nuclei by 0.4M KCl bound also to dihydrotestosterone in a high affinity manner. Cytosol prelabeled with R 1881 was bound to the nuclei in a nonsaturable process, and the extraction pattern of R 1881 by 0.4M KCl from the nuclei was almost identical to that in the case of dihydrotestosterone as the ligand. These results suggested that a part of the cytosolic protein which bound to R 1881 entered the nuclei where it bound to nuclear such components as dihydrotestosterone-binding protein.

Topics: Cell Extracts; Chromatography, Gel; Cyproterone; Cytosol; Dihydrotestosterone; Estrenes; Humans; Male; Metribolone; Prostatic Hyperplasia; Protein Binding; Tritium

Occurrence of steroid hormone receptor has been evaluated in 30 prostatic cancer-bearing patients: 5 alpha-dihydrotestosterone receptor (DHTR) occurrence was correlated with both tumor grade of differentiation and clinical response to hormone therapy.

Topics: Aged; Androgen Antagonists; Cyproterone; Dihydrotestosterone; Estradiol; Humans; Hydrocortisone; Male; Middle Aged; Progesterone; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Steroid

The effect of cyproterone acetate (CA) on experimentally induced benign prostatic hyperplasia (BPH) in the castrated dog was investigated. BPH was induced by 6 months' treatment with 3 alpha-androstanediol (3 alpha-diol) alone and in combination with 17 beta-oestradiol (Oe2). RNA, DNA and zinc content of the glands were determined in addition to histological examination and measurement of the prostates. Two different types of prostatic enlargement were observed. First, 3 alpha-diol induced typical diffuse canine hyperplasia with replacement of functional activity. DNA, RNA and the zinc content of total glands were increased compared with intact controls. Second, 3 alpha-diol plus Oe2 produced on the one hand a more striking increase of prostatic weights, but on the other a loss of typical morphological structure and function. Histologically, transformation of simple glandular epithelium into stratified squamous metaplasia occurred in addition to stimulation of fibromuscular tissue. Biochemically, a relative decrease of DNA per mg tissue was measured with a fall in the RNA to DNA ratio and zinc to the values of castrates. Administration of CA resulted in an abolition of the 3 alpha-diol effect. Biochemical determinations and histological examinations revealed an effect similar to castration after treatment with 3 alpha-diol plus CA. After treatment with 3 alpha-diol plus Oe2 plus CA fibromuscular stimulation as an oestrogen effect predominated in addition to glandular atrophy and metaplastic changes, especially in prostatic ducts. Epithelial hyperplasia is an effect of 3 alpha-diol, whereas metaplastic proliferation only occurs in oestrogenized and androgenized dogs. In both types of prostatic enlargement CA prevents development of hyperplastic prostate.

Topics: Androstane-3,17-diol; Androstanes; Animals; Castration; Cyproterone; DNA; Dogs; Estradiol; Male; Organ Size; Prostate; Prostatic Hyperplasia; RNA; Zinc

An immunocytochemical technique was described to test for immunoreactive prolactin (PRL) and growth hormone (GH) in spontaneous and experimentally induced hyperplastic and neoplastic lesions of the prostate and mammary gland. The dog was used as an animal model. The specificity and validity of the immunocytochemical staining procedure and of the antisera to canine PRL and canine GH can be regarded as established for the demonstration of PRL- and GH-dependent staining respectively. In mammary and prostatic tissues, both endogenous PRL and GH as well as intracellular free binding sites (for exogenous PRL and GH) were detected immunocytochemically. The technique presented seems to be an important tool to localize putative target sites for pituitary hormones in hormone-dependent hyperplasia and neoplasia.

Topics: Androstenediol; Animals; Castration; Cyproterone; Dogs; Estradiol; Female; Growth Hormone; Immunoenzyme Techniques; Male; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Prolactin; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Dog prostates under defined hormonal influences were investigated by light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The normal acinar cell apices exhibited well-developed, densely packed microvilli. TEM demonstrated numerous secretory granules, indicating a high secretory activity. Following castration, the acinar cells of the dog prostate showed rounded apices. Most of the microvilli disappeared and only knob-like protrusions were seen. Castrated dogs following administration of 3 alpha-androstandiol showed fewer microvilli than the controls; however, a well-developed undulating surface could be observed. Castrated dogs given 3 alpha-androstandiol and cyproterone acetate showed almost completely atrophic glandular cells. Prostates of dogs with spontaneous benign prostatic hyperplasia (BPH) were characterized by pleomorphism of cell shapes and surfaces. The different hormonal influences induced changes of the prostatic surface structures and secretory activity.

Topics: Androstanols; Animals; Castration; Cyproterone; Cytoplasmic Granules; Disease Models, Animal; Dogs; Drug Interactions; Estradiol; Gonadal Steroid Hormones; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Prostate; Prostatic Hyperplasia

The antiandrogen, cyproterone acetate (CPA), prevents development of prostatic hyperplasia, induced in castrated dogs by a 6 month-treatment with 5 alpha-androstane-3 alpha, 17 beta-diol (A)alone or in combination with 17 beta-oestradiol (E2). The immunoperoxidase technique was used to study functional cell types in the pars distalis of the pituitary gland and to detect growth hormone (GH) and prolactin (PRL) target sites in the prostate gland. Homologous radioimmunoassays for estimation of serum canine GH and PRL concentrations were also performed. Treatment with the combinations A + E2 and A + E2 + CPA resulted in morphological indications of stimulated GH and PRL cells and depressed gonadotrophs. This correlates well with an increase in PRL-dependent staining in glandular epithelium and fibromuscular tissue of the prostate gland. However, basal serum PRL and GH levels were not significantly affected. Treatment with A and A + E2 stimulated, while additional treatment with CPA clearly suppressed adrenocorticotrophin/melanotrophin (ACTH/MSH) cells. These findings indicate that an endocrine imbalance in hypothalamic-pituitary-adrenal function may be involved in induction and prevention of prostatic hyperplasia in the dog.

Topics: Androstane-3,17-diol; Animals; Castration; Cyproterone; Dogs; Estradiol; Growth Hormone; Male; Pituitary Gland, Anterior; Prolactin; Prostate; Prostatic Hyperplasia

A new procedure has been developed to purify prostatic cell nuclei and to achieve a high yield of nuclear material for study. This technique allowed the investigation of the enzyme 5-alpha-reductase and its relationship to the translocation of dihydrotestosterone and androgen receptors into the nucleus of the prostatic cell. The studies revealed that 5-alpha-reductase was localized chiefly to the stromal components of all types of prostatic tissue. Although there is a higher concentration of dihydrotestosterone in carcinoma tissue the 5-alpha-reductase activity is low. Studies on the effect of androgens and antiandrogens on nuclear uptake of androgen revealed that androgens are potent stimulants of receptor translocation, while antiandrogens stimulate little or no translocation.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Androgen Antagonists; Animals; Cyproterone; Dihydrotestosterone; Estrenes; Flutamide; Humans; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Rats; Receptors, Androgen; Receptors, Steroid

The effect of various steroidal compounds on the binding of the androphilic protein to dihydrotestosterone in the cytosol of tissues of human benign prostatic hypertrophy was examined. Androgens, as well as estrogens and gestagens showed an inhibitory effect on the binding. Non-steroidal anti-androgens were revealed to be weak inhibitors on the binding. Two androphilic proteins were observed in Sephadex G-200 chromatography in fractions eluted at the void volume and in fractions appearing at the site of IgG, and the rate of inhibition on the binding of both fractions by various steroids was compared. The rate of inhibition by various compounds was generally higher in the IgG fraction than in the void volume fraction. When the ligand and inhibitors were incubated with the cytosol prior to fractionation by Sephadex chromatography, rate of inhibition was lower than that obtained when the ligand and inhibitors were reacted with fractions after chromatography. Implications of the difference observed in these two experiments are not clear at this moment. The results obtained by the protamine precipitation experiment were almost the same as those by the experiment using the extract of the unfractionated acetone-dried cytosol, therefore, the protamine procedure does not seem to precipitate the tissue specific androphilic protein specifically.

Topics: Androgens; Culture Techniques; Cyproterone; Cytosol; Dihydrotestosterone; Estradiol; Estrogens; Humans; Male; Progestins; Prostate; Prostatic Hyperplasia; Protein Binding

The response of 3H-testosterone and 3H-dihydrotestosterone to the administration of cyproterone acetate (CA) over a period of 5 days was investigated. Both tracers were injected intravenously in patients with benign prostatic hypertrophy. Blood was withdrawn for up to 5 h. Benign prostatic hypertrophy tissue was obtained by transurethral resection. Nine patients served as controls. Eleven patients received 300 mg CA intramuscularly. Cyproterone acetate suppressed testosterone and FSH, but not LH. 3H-testosterone was cleared more rapidly from plasma in the patients given CA presumably due to increased metabolism in the liver. 3H-dihydrotestosterone, however, remained virtually uninfluenced. Moreover, CA did not significantly alter the 3H-testosterone and 3H-dihydrotestosterone uptake and metabolism within prostatic tissue.

Topics: Aged; Cyproterone; Dihydrotestosterone; Follicle Stimulating Hormone; Humans; Kinetics; Liver; Luteinizing Hormone; Male; Prostate; Prostatic Hyperplasia; Testosterone

It is reported on the possibilities of the application of anti-androgenics, especially of cyproterone acetate. The indication extends to hirsutism, sexual deviations, growth disturbances in pubertas praecox as well as diseases of the prostate. Particularly strong standard are to be applied in the treatment of fertile women, as there exists the danger of an intrauterine feminisation of male foetuses, when a pregnancy was not absolutely excluded. Side-effects and results of animal experiments are mentioned. The therapeutic mechanism of the anti-androgenics can be explained with the help of a concurrency mechanism at the androgen receptor or acceptor.

Topics: Acne Vulgaris; Animals; Cricetinae; Cyproterone; Female; Gynecomastia; Hirsutism; Humans; Libido; Male; Menstruation Disturbances; Paraphilic Disorders; Pregnancy; Prostatic Hyperplasia; Puberty, Precocious; Rats

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Cyproterone; Cytoplasmic Granules; Dogs; Epithelium; Exocytosis; Lysosomes; Male; Prostate; Prostatic Hyperplasia

Topics: Androgen Antagonists; Animals; Cyproterone; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Male; Organ Size; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Testosterone; Transplantation, Heterologous

Topics: Androgen Antagonists; Cyproterone; Germany, West; Gestonorone Caproate; Humans; Male; Progestins; Prostatic Hyperplasia; Testosterone

A technique for the demonstration of a human steroid and organ-specific prostate cytosol receptor is described. Tissue from 17 patients with benign prostatic hypertrophy was incubated in Eagle's medium with 3H-testosterone (T) .06 nM following pre-incubation with an anti-androgen. The minces were homogenized and the cytosol fraction obtained. The cytosol was then fractionated on a duo-gel column of G-50 Sephadex over Bio-gel A 1.5m and fractions counted for 3H, assayed for protein and plotted graphically. Three main peaks were seen. Only the second peak (approximately 150,000 mol wt), which contained predominantly dihydrotestosterone (DHT), was significantly and reproducibly inhibited by 2.1 muM cyproterone acetate (Cyp A) pre-incubation. This inhibiton was considered a specific indicator for receptor since Cyp A at muM had little effect (less than 10%) on 3H-DHT binding to plasma. Similar results were noted for other anti-androgens tested, but cortisol and etiocholanolone had no effects on 3H-5alpha DHT binding to prostate cytosol. Steroid-protein peaks for fractionated human thyroid, muscle, and spleen cytosol were not inhibited by Cyp A. Fractionated kidney cytosol contained a 3H-T-binding protein peak which was significantly decreased by Cyp A. Pronase incubation and heating at 50 C for 30 min both resulted in either a significant decrease or complete loss of receptor. Gel filtration analysis of 3H-cytosol derived from human prostate minces pre-incubated with and without Cyp A, provides a relatively rapid technique for the demonstration of cytosol receptor in approximately 80% of prostates from patients with benign prostatic hypertrophy.

Topics: Aged; Cyproterone; Cytosol; Dihydrotestosterone; Etiocholanolone; Humans; Hydrocortisone; In Vitro Techniques; Male; Middle Aged; Organ Specificity; Prostate; Prostatic Hyperplasia; Receptors, Cell Surface

Topics: Androgen Antagonists; Animals; Cyproterone; Female; Humans; Infertility, Female; Libido; Male; Prostatic Hyperplasia; Puberty, Precocious; Rats; Spermatogenesis

Topics: Carbon Radioisotopes; Cell Nucleus; Chromatography, Gel; Chromatography, Paper; Chromatography, Thin Layer; Cyproterone; Cytoplasm; Depression, Chemical; Diethylstilbestrol; Dihydrotestosterone; Estradiol; Estrone; Ethinyl Estradiol; Humans; Hydrocortisone; In Vitro Techniques; Male; Prostate; Prostatic Hyperplasia; Protein Binding; Tritium

The conversion of carbon-14-testosterone (T) to 5alpha-dihydrotestosterone (DHT) and androstanediol (A-diol) was studied in vitro using a crude homogenate of prostate from patients with benign prostatic hypertrophy. Under standard conditions, the mean conversion to DHT was 70 + or -1 (standare error, SE)% and to A-diol 14 + or -1 (SE)%. Addition of various antiandrogens and other substances decreased the T to DHT conversion to 0-55% and the T to A-diol to 0-10%. The most potent inhibitors were desoxycorticosterone and progesterone. Estradiol-17beta, cyproterone acetate, medrogestone, medroxyprogesterone acetate, estriol and 4'-nitro-3'trifluoromethylisobutyramilide were also effective inhibotors. To determine whether this effect might be significant in vivo, similar conversion studies were carried out on prostatic tissue obtained from 3 patients who had received oral medrogestone for 1-2 weeks. T to DHT was reduced to 12.2 + or -2.8 (SE)% and T to A-diol to 6.5 + or -1.0 (SE)%. The ability of such compounds to inhibit DHT formation represents 1 mode of action which may account at least in part for their efficacy in the treatment of benign prostatic hypertrophy.

Topics: Androgen Antagonists; Androstanes; Anilides; Carbon Radioisotopes; Cyproterone; Desoxycorticosterone; Dihydrotestosterone; Estradiol; Estriol; Humans; Hydrocarbons, Fluorinated; In Vitro Techniques; Male; Medrogestone; Medroxyprogesterone; Nitro Compounds; Progesterone; Progestins; Prostate; Prostatic Hyperplasia; Testosterone; Tritium

Topics: Acid Phosphatase; Aged; Culture Media; Cyproterone; Dihydrotestosterone; Esterases; Estradiol; Glucuronidase; Histocytochemistry; Humans; Leucyl Aminopeptidase; Male; Middle Aged; Organ Culture Techniques; Progesterone; Prostate; Prostatic Hyperplasia; Steroids; Testosterone; Thymidine; Tritium

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.

Topics: Acetates; Aged; Androgen Antagonists; Androstenedione; Biological Transport; Carbon Isotopes; Cyproterone; Dihydrotestosterone; Humans; Male; Middle Aged; Pregnadienes; Prostate; Prostatic Hyperplasia; Testosterone; Time Factors; Tritium