SEARCH · Search PubMed

Results for “Cyproterone”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,081 records · Page 60Linked to original sources

PubMed1996

Use of rat and human liver slices for the detection of steroid hormone-induced DNA-adducts in vitro by means of the (32)P-postlabeling technique.

Precision cut liver slices from humans and rats were used to investigate the covalent binding of xenobiotics to the DNA by means of the (32)P-postlabeling technique. Human liver slices were incubated with the structurally related steroid hormones chlormadinone acetate (5 mu g/ml), cyproterone acetate (0.01-5 mu g/ml), megestrol acetate (5 mu g/ml), and the positive control 2-aminofluorene (0.01-5 mu g/ml), which is known for its marked ability to form DNA-adducts in vivo. Rat liver slices were incubated with cyproterone acetate in concentrations of 0.1, 1, and 5 mu g/ml. The functional viability and metabolic activity of the slices were shown to be sufficiently maintained during the incubation time by measurement of the intracellular K(+)-content and the metabolic turnover of the model substrate 7-ethoxycoumarin, respectively. All three test substances and the control induced DNA-adducts in human liver slices, however, with a different adduct pattern. While the total DNA-adduct levels obtained with cyproterone acetate and megestrol acetate were in the same order of magnitude (on average 1000 DNA-adducts/10(9) nucleotides after incubation with 5 mu g /ml), the relative adduct labeling calculated for chlormadinone acetate was about 400. Following in vitro incubation of rat liver slices with cyproterone acetate, the relative adduct labeling values increased proportionally with increasing concentrations and added linearily to in vivo generated DNA-adducts. At the level of liver slices, different DNA-adduct patterns were induced by cyproterone acetate in rat and man. In contrast to the finding of others, using rat hepatocytes, the relative adduct labeling values of cyproterone acetate and megestrol acetate were in the same order of magnitude after incubation with human liver slices. The present study indicates that liver slices are a useful tool to investigate the in vitro DNA-adduct inducing potential of xenobiotics.

Adult↗

PubMed2000

Dramatic suppression of plasma and urinary prostate specific antigen and human glandular kallikrein by antiandrogens in male-to-female transsexuals.

PURPOSE: Prostate specific antigen (PSA) and human glandular kallikrein (hK2) are mainly produced by the prostate and their genes are regulated by androgens through the androgen receptor. We determine whether PSA and hK2 change significantly in plasma and urine after antiandrogen treatment in male-to-female transsexuals. MATERIALS AND METHODS: Plasma and urine PSA and hK2 were measured with highly sensitive immunofluorometric procedures capable of detecting within 1 or 6 ng./l. PSA or hK2, respectively. Study groups consisted of 10 men treated with cyproterone acetate only (group 1), 15 transdermal estradiol plus cyproterone acetate (group 2) and 31 ethinyl estradiol plus cyproterone acetate (group 3). Plasma and urine samples were collected before initiation of treatment as well as after 4 months of hormonal therapy. For a subset of group 3 patients blood and urine samples were also obtained after 12 months of treatment. RESULTS: Cyproterone acetate, a steroidal antiandrogen, alone or with estradiol was able to suppress greater than 90% of plasma and urinary PSA and hK2 concentration after 4 or 12 months of therapy. CONCLUSIONS: Cyproterone acetate therapy causes dramatic suppression of plasma and urinary PSA and hK2 in men without prostate cancer. Since cyproterone acetate is used for prostate cancer treatment, suppression of PSA after hormonal therapy may not accurately reflect therapy success in reducing tumor burden.

Adolescent↗

PubMed1981

Comparative effects and mechanisms of castration, estrogen anti-androgen, and anti-estrogen-induced regression of accessory sex organ epithelium and muscle.

We examined the effects and mechanisms of action of various endocrine manipulations on the epithelium and muscle preparations of the guinea pig seminal vesicle. Castration, which reduced the plasma testosterone level to 10 percent of normal, caused approximately 80 per cent reductions in epithelium wet weight and RNA and DNA contents. Estradiol benzoate effected similar reductions in plasma androgen and epithelial cell function in intact males. Reduction in plasma androgen level accounted for the estrogen-induced epithelial regression; no antiandrogenic effect of estrogen on the epithelium was detectable. All anti-androgens tested, flutamide, spironolactone, and cyproterone acetate, reduced epithelium weight in intact animals. Studies of the mechanism of cyproterone acetate action indicated its effects were attributable solely to an anti-androgenic action on the epithelium. The anti-estrogens, tamoxifen and nafoxidine, had no effect on the epithelium of intact animals when tested alone or in combination with cyproterone acetate. Regression of seminal vesicle muscle occurred only after castration or treatment of intact animals with cyproterone acetate. The action of cyproterone acetate on the muscle was attributable to blockade of the androgenic stimulus. The drug had no effect on plasma testosterone or estradiol levels and had no anti-estrogenic activity. In intact males estradiol reduced plasma testosterone to castrate levels, but did not alter muscle weight and nucleic acid levels. The potential deleterious effects of reduced plasma testosterone on the muscle were surmounted by direct estrogenic stimulation of the tissue. The anti-androgens, flutamide and spironolactone, and the anti-estrogens, tamoxifen and nafoxidine, had no effect on the muscle of intact males. Inasmuch as the regressive effects of castration on the epithelium and muscle can be duplicated in intact animals only by treatment with cyproterone acetate, this particular drug may provide the most effective nonsurgical treatment of prostatic neoplasia.

Androgen Antagonists↗

PubMed1983

Steroid inhibitors of androgen-potentiated actions on skin.

Antiandrogens, such as cyproterone acetate, and oestrogens both inhibit sebaceous secretion in rats and have a potentiality for the treatment of hirsutism and acne in the human female. However, they act at different points. In castrated rats treated with testosterone, 3 micrograms/day oestradiol produced a greater decrease in sebum secretion than a dose of cyproterone acetate over 1000 times larger; moreover the antiandrogen reduced the incidence of sebaceous mitoses whereas the oestradiol did not. In hirsute women, oral administration of 100 mg of cyproterone acetate daily caused a 40% reduction in sebum secretion within 10 days; a further 20% was subsequently produced by combined therapy with cyproterone acetate and ethinyloestradiol. Significant decreases in the diameter and rate of growth of thigh hairs were not established until around the fourth monthly cycle of treatment. The actions were believed to be mainly peripheral, though contributory factors could also have been the small but significant reductions in plasma androgens produced by the antiandrogen, and the marked rise in sex hormone binding globulin produced by the oestrogen. That it is theoretically possible for cyproterone acetate or oestradiol to act locally follows from an unequivocal demonstration that either compound produced a local depression of sebum secretion when applied topically to rats.

Androgen Antagonists↗

PubMed1988

Relative effectiveness of alternative androgen withdrawal therapies in initiating regression of rat prostate.

From a large number of potentially effective androgen withdrawal regimens including bilateral orchiectomy, estrogens, antiandrogens and LHRH agonists alone or in combinations, we compared the ability of 12 different treatment options to mimic the acute results of surgical castration on the rat prostate. Agents were administered s.c. in clinical doses to groups of male rats daily for three days. On day 4 the prostatic tissue was removed and analyzed by conventional methods for whole-tissue and nuclear concentrations of dihydrotestosterone, nuclear androgen receptor and cytoplasmic androgen receptor. Castration-like changes were most pronounced with the synergistic combinations of cyproterone acetate + low-dose diethylstilbestrol, and megestrol acetate + low-dose diethylstilbestrol. Comparing the effectiveness of single agents, low-dose diethylstilbestrol was superior to cyproterone acetate, megestrol acetate, flutamide, leuprolide and RU23908. Leuprolide combined with flutamide was superior to leuprolide + cyproterone acetate, leuprolide + cyproterone acetate + low-dose diethylstilbestrol or leuprolide + RU23908 after three days of administration; however, this advantage disappeared when the treatments were extended to seven days. The observations indicate that the most potent androgen withdrawal therapies such as cyproterone acetate + low-dose diethylstilbestrol and megestrol acetate + low-dose diethylstilbestrol at best approximate but do not surpass the early effects of surgical castration. During the same time course, other regimens are characterized by a slower onset of action and a lesser degree of suppression of androgenic mechanisms within the cell.

Anilides↗

PubMed1985

Effects of steroid hormones and antihormones in cultured cells.

Mouse L-929 fibroblasts contain androgen (AR), estrogen (ER) and glucocorticosteroid receptors (GR). The addition of androgens and estrogens (10 to 50 nM) to the culture medium stimulated cell growth and this growth stimulation was inhibited when the corresponding anti-hormones (cyproterone acetate or tamoxifen, 100 nM) were present at the same time. Glucocorticosteroids (10 to 100 nM) had negative effects on cell growth leading even to cell death over 1 microM concentrations. The addition of a new antiglucocorticosteroid RU 486, inhibited the negative effects of glucocorticosteroids. RU 486 displays also anti-progesterone activity, but as L-929 cells have no progesterone receptor, only the anti-glucocorticosteroid action of this new compound was studied. Cell adhesiveness to culture plates was increased by androgen or estrogen, but decreased by glucocorticosteroid and again, the corresponding anti-hormones abolished these positive or negative effects. All these observations can be made in serum-free culture medium supplemented with insulin but not with other hormones, proteins or growth factors. Cyproterone acetate, tamoxifen and RU 486 have specific affinity for AR, ER and GR, respectively. After incubation of whole cells with 3H-tamoxifen or 3H-RU 486, accumulation of either estradiol or glucocorticosteroid receptor complexes in the nuclear fraction of the cell was observed. A tamoxifen-resistant clone of L-929 cells was selected in serum-free medium. This variant had about 50% less ER than tam-sensitive L-929 cells and also less specific antiestrogen binding sites which were found in the particulate fraction of the cells. Shionogi SC-115 mammary cancer cells contain AR and ER. In the presence of testosterone (50 nM) a considerable difference of cell growth was observed. Testosterone increased cell proliferation, and the anti-androgen cyproterone acetate (100 nM) completely inhibited this growth stimulation. RU 486 (100 nM) showed also some antagonistic effect on androgen induced cell growth. The shape of cells cultured with or without androgens was completely different. In the presence of testosterone, clonal growth of the cells was observed with no contact inhibition, whereas in the absence of hormone, cells formed a monolayer. No clonal growth was observed when cyproterone acetate (100 nM) was present at the same time as testosterone in the culture medium. Both testosterone and cyproterone acetate were bound to AR. In the murine thymoma cell lines W7TB and T1M1b, RU 486 is a strong antagonist of the glucocorticosteroid induced cytolytic response.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

The clinical and endocrine assessment of three different antiandrogen regimens combined with a very long-acting gonadotrophin-releasing hormone analogue.

Tumor flare is reported in up to 40% of patients treated with gonadotrophin-releasing hormone analogues for prostate cancer. In order to investigate the optimal way to eliminate tumor flare, we have treated patients with one of three different antiandrogen regimens used in combination with gonadotrophin-releasing hormone (GnRH) agonist. The early results of this study are presented here. Thirty patients with advanced symptomatic disease were randomized to receive either cyproterone acetate 50 or 100 mg three times daily or flutamide 250 mg three times daily given for 1 week before and during the first month of GnRH agonist treatment. The endocrine profiles of these patients were compared with those of historic controls treated with depot agonist alone. Three patients treated with low-dose cyproterone acetate and one with flutamide developed a transient exacerbation of their disease. No patients treated with the higher-dose cyproterone acetate regimen developed tumor flare. No patients treated with cyproterone acetate had an increase in serum testosterone above baseline following depot GnRH agonist implantation. All patients treated with flutamide had increases in serum testosterone, but this did not significantly increase further with implantation. This study suggests that all patients receiving GnRH agonist treatment should be pretreated with cyproterone acetate 100 mg three times daily for 1 week before implantation and for the first treatment month.

Aged↗

PubMed2006

Spontaneous reporting of hepatotoxicity associated with antiandrogens: data from the Spanish pharmacovigilance system.

PURPOSE: To analyse the type and main features of the hepatotoxicity induced by steroidal and non-steroidal antiandrogens spontaneously reported by physicians, pharmacists and nurses. This analysis could increase the information related to these adverse reactions mainly available from the published isolated cases. METHODS: Using the Spanish Pharmacovigilance database we searched for spontaneous reports recorded since the date of approval of each antiandrogen up to the present time. We analysed the frequency of liver disorders, the preferred terms coded, the presence of other hepatotoxic drugs, and the characteristics of cases of hepatitis. RESULTS: Liver disorders were the most common adverse reactions associated with flutamide and bicalutamide, but not with cyproterone acetate. 'Hepatitis' and 'cholestatic hepatitis' were the most frequent terms coded. In 38% of the reports related to cyproterone acetate, 18% of those related to flutamide and 33% of those related to bicalutamide the patient had simultaneously received other hepatotoxic drugs. The disproportionality analysis of hepatitis showed a strong association with flutamide and a weak association with bicalutamide and cyproterone acetate. Mean doses of flutamide and bicalutamide were very close to their defined daily dose (DDD) to treat prostate cancer, although in the case of cyproterone acetate it was slightly higher. The latency period of hepatitis was between 3 and 10 months for the three antiandrogens, and the recovery period was shorter (0.5-3 months). The majority of the reported cases of hepatitis evolved favourably. CONCLUSION: Our results highlight the hepatotoxic potential of flutamide compared to cyproterone acetate. The data related to bicalutamide should be cautiously considered due to the smaller number of reports.

Adverse Drug Reaction Reporting Systems↗

PubMed1986

Potentiation of the depression by adenosine of rat cerebral cortical neurones by progestational agents.

The effects of four progestational agents pregnenolone sulphate, cyproterone acetate, norethindrone acetate and progesterone, on adenosine-evoked depression of the firing of rat cerebral cortical neurones have been studied. When applied iontophoretically, pregnenolone sulphate, cyproterone, and norethindrone enhanced the actions of iontophoretically applied adenosine and failed to potentiate the depressant effects of adenosine 5'-N-ethylcarboxamide and gamma-aminobutyric acid. Cyproterone acetate (50 micrograms kg-1) and progesterone (200 micrograms kg-1) administered intravenously enhanced the depressant actions of iontophoretically applied adenosine. When applied by large currents, cyproterone, and less frequently norethindrone, depressed the firing of cerebral cortical neurones. The depressant effects of cyproterone were antagonized by caffeine. Pregnenolone sulphate tended to excite cortical neurones but neither this action, nor its potentiation of adenosine were reproduced by application of sulphate ions. It is hypothesized that some of the psychotropic actions of progestational agents may involve an enhancement of 'purinergic' tone in the central nervous system.

Adenosine↗

PubMed1976

[The fine structure of the rat pineal and the influence of anti-androgens and castroation].

The pineal body, along with the hypothalamus-hypophysis system, is in the centre of sexual hormone regulation and, in addition to other functions, develops an antigonadotropic action through its organ specific hormone (melatonin). In order to clarify further open questions and to analyse more closely the morphology of the fine structure of the organ, light and electron microscopic studies were made of the pineal bodies of sexually mature male rats after hormonal castration by the administration of cyproterone and cyproterone acetate. The findings were compared with results obtained in the pineal bodies of surgically castrated animals of the same strain. Epiphysectomy was performed 3, 6, 9 and 12 weeks after castration or application of antiandrogen. In the pineal bodies, "light" and "dark" pineal cells and an interstitial cell form could be detected electronmicroscopically. The interstitial cells are found localised near the vessels in particular; their ramifications reach into the perivascular cleft. The light pineal cells preponderate and react essentially in the series; they are therefore considered as the really active form of parenchyma cells. Increased cell activity is already observed three weeks after treatment with antiandrogen: the nucleoli are enlarged, the ribosomes, the mitochondria and ergastoplasm are increased, the endoplasmic reticulum quantified and extended, and also the Golgi regions. The cells are consequently enlarged. Lysosomes also appear which frequently enter the liposomes. The changes in the liposomes after application of antiandrogen are remarkable. Initially they are evacuated, partially drawn out. Later the liposomes are enlarged and increased and often fill the cell body. These pineocytes form an appendage to the castration cells of the hypophysis. The liposomes are in a very close spatial, formal genetic relationship to the Golgi apparatus and to the rough walled reticulum. The larger liposomes apparently arise also through the confluence of smaller ones. Three structural elements of the liposomes could be indentifed: a homogenous, a lamellar and a granular component. The fine morphological reactions are most marked after cyproterone acetate. For the first time, bundles of "microtubuli" are described, the significance of which is not yet clear. They probably arise from the endoplasmic reticulum, they are only found after cyproterone acetate and are presumably due to the gestagen component of the cyproterone acetate. These structures have not previously been observed, either in pineal bodies or in other organs. The structures found after antiandrogen are not so outstandingly recognisable after surgical castration. The biological differences of the surgical compared with hormonal castration therefore seem to be reflected in the cell picture of the pineocytes. Consequently, the pineal body, after treatment with antiandrogen, shows cytostructural changes similar to those of increased anabolism...

Animals↗

PubMed1984

Ultrastructural evidence for endogenous testosterone immunoreactivity in the pituitary gland of the rat.

Several attempts have been made to localize steroids by means of immunocytological techniques. However, these methods were found inadequate for detecting steroids bound to their receptors. To localize endogenous testosterone (T) in its target cells at the ultrastructural level, an immunocytological technique was performed on ultrathin sections obtained by cryo-ultramicrotomy. T was detected in the pituitary glands obtained from intact male or female rats and castrated rats, but not in castrated + adrenalectomized rats. Animals were also injected either with testosterone, with other steroids (estradiol, progesterone, corticosterone) or with an androgen antagonist (cyproterone acetate). In addition, some ultrathin sections were preincubated either with phosphate buffers of various pH, corticosterone, cyproterone acetate solution, or with T solution. The content of T in the pituitary before and after fixation was measured by radioimmunoassay; it decreased after fixation. T immunoreactivity was localized in the gonadotropic cells only, both in the male and female rats. At the subcellular level, the immunoreactivity was detected in the cytoplasmic matrix and in the nucleus. Immunoreactive T disappeared 1) in rats after castration + adrenalectomy; by means of radioimmunoassay no T was measured in these pituitary glands; 2) in rats injected with 25 micrograms/rat of cyproterone acetate; 3) after preincubation of pituitary sections on a drop of cyproterone acetate (1 X 10(-6) M). The immunocytological reaction was not modified when the rats were injected with estradiol, progesterone or corticosterone (1 mg/rat), or after preincubation of the sections with corticosterone (1 X 10(-3 M), or a buffer solution at pH 7.6. Lower or higher pH values led to a strong decrease in the immunoreactivity. After injection of T (15 micrograms/rat) the immunocytological reaction was more abundant in the nucleus and less in the cytoplasm. The immunoreactivity was again observed when the sections were preincubated with cyproterone acetate solution and then with T solution. These data suggest that T can be detected by means of immunocytochemistry. It is probably bound to a specific binding site.

Adrenal Glands↗

PubMed1986

Pharmacology of antiandrogens.

Principally, antiandrogens affect all androgen-dependent organs and functions as for instance accessory sexual glands, spermatogenesis, skin and skin appendages, libido and potency, male sexual differentiation, longitudinal bone growth and bone maturation. Pharmacologically, it is important to distinguish between the steroidal antiandrogens of the cyproterone acetate type and the nonsteroidal pure antiandrogens (flutamide, anandrone). For the clinical use of cyproterone acetate and similar antiandrogens in both men and women the three main properties are important: Cyproterone acetate is antiandrogenic, it is a quite potent progestogen and it is antigonadotrophic. Based on pharmacological and biochemical backgrounds cyproterone acetate is used in the following indications: Androgen mediated disorders of the skin such as acne, seborrhoea, hirsutism, alopecia, advanced prostatic carcinoma, precocious puberty and male hypersexuality. In order to avoid undesired systemic side effects local application of antiandrogens, e.g. of cyproterone acetate, has been tried several times. All these attempts have failed probably because insufficient concentration of the antiandrogen at the pilo sebaceous unit. 17 alpha-propylmesterolone is active when given topically (hamster ear model) and has no systemic antiandrogenic effects. This antiandrogen is highly lipophilic and does penetrate preferentially through the hair follicle as has been shown by autoradiography.

Acne Vulgaris↗

PubMed1991

Sex difference in triglyceride/fatty acid substrate cycling of rat adipose tissue: indirect regulation by androgens.

Male Sprague-Dawley rats displayed significantly higher rates of triglyceride/fatty acid (TG/FFA) substrate cycling in subcutaneous, perigenital, and mesenteric white adipose tissue, compared to females. To investigate possible regulation via androgens and estrogens, male rats were treated with the androgen antagonist, cyproterone acetate (10 mg daily in subcutaneous injections), or estradiol polyphosphate (0.3 mg intramuscularly, given as a single dose). Estradiol treatment did not affect TG/FFA cycling. Treatment with cyproterone acetate significantly decreased TG/FFA cycling in perigenital (epididymal) tissue. This effect could however largely be ascribed to concomitant inhibition of food intake by cyproterone acetate. The effects of cyproterone acetate on the two axes of TG/FFA cycling (lipolysis and re-esterification) were further studied in vitro. Norepinephrine-stimulated glycerol release from perigenital adipocytes was inhibited, whereas activities of esterification enzymes (GPAT and PPH) was essentially unaffected. We conclude that androgens seem to affect TG/FFA cycling indirectly via the lipolytic axis.

Adipose Tissue↗

PubMed1986

Pre- and postnatal influence of an estrogen antagonist and an androgen antagonist on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats.

The volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) of the rat brain is severalfold larger in adult male rats than in adult females. This sex difference in brain structure was previously shown to develop under the influence of androgenic and estrogenic hormones during the perinatal period. We tried to clarify the differential role played by androgens and estrogens during development and differentiation of the SDN-POA by treating male and female rats during an extended pre- and postnatal period either with the estrogen antagonist tamoxifen or with the androgen antagonist cyproterone acetate. Treatment with tamoxifen did not alter serum levels of testosterone in male rats during the perinatal period, but it inhibited development and differentiation of the SDN-POA. Pre- and postnatal treatment of male rats with cyproterone acetate resulted in female phenotypic appearance, but it had no influence on differentiation of the SDN-POA. Perinatal treatment of female rats with tamoxifen resulted in permanent anovulatory sterility, but did not influence SDN-POA differentiation. Treatment of female rats with cyproterone acetate had no influence on SDN-POA differentiation or on the capacity to ovulate. Since pre- and postnatal treatment of male rats with cyproterone acetate is known from previous studies to femenize sexual behavior patterns and to retain the mode for cyclic gonadotropin release, and since the same treatment did not influence differentiation of the SDN-POA in the present study, it may be concluded that the SDN-POA is not directly involved in the control of female sexual behavior and in the control of the gonadotropic hormone release pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Biopotency and site of action of drugs affecting testicular steroidogenesis.

The effect of etomidate (an anaesthetic), epostane (WIN 32729; an inhibitor of ovarian and adrenal steroidogenesis) and cyproterone acetate (an antiandrogen) on testosterone secretion from mouse Leydig cells stimulated with LH (5 i.u./l) was tested. The concentration of drug which inhibited testosterone secretion by 50% was 11.5 +/- 1.1 (S.E.M.) mumol/l for cyproterone acetate, 1.2 +/- 0.2 mumol/l for etomidate and 0.23 +/- 0.03 mumol/l for epostane. The effect of all three drugs on testicular steroidogenesis was completely reversible. Thus testicular cells which had been washed after exposure to a greater than 95% inhibitory dose of drug responded in a similar manner to hormone stimulation as cells similarly washed and which had not been exposed to the drug. The sites of the antisteroidogenic effect of epostane, etomidate and cyproterone acetate were established using a method based on the sequential stimulation by the exogenous precursor steroids of the various steps leading to the biosynthesis of testosterone. It was concluded that etomidate acts at the sequence between LH binding and pregnenolone production, epostane acts at 3 beta-hydroxysteroid dehydrogenase and cyproterone acetate inhibits 3 beta-hydroxysteroid dehydrogenase and C17,20-lyase.

Androgen Antagonists↗

PubMed1975

Androgen-dependent accumulation of carnitine by rat epididymis after injection of [3H]butyrobetaine in vivo.

After i.m. injection of [3H]butyrobetaine into rats, the accumulation of carnitine into the epididymis, prostate gland, seminal vesicles, testis and heart was studied. The concentration of radiolabeled carnitine into the cauda epididymis increased linearly with time up to 72 h after the injection of the precursor, while its level in the prostate and seminal vesicles decreased rapidly. Very low levels of carnitine were found in the testis. Castration reduced the carnitine accumulation by cauda epididymis to 6% of the control levels while treatment of castrated animals with testosterone propionate (500 mug/day) partly restored the carnitine uptake. Similar treatment with 17beta-oestradiol valerate or 17alpha-hydroxyprogesterone had no effect. Surprisingly, cyproterone acetate (5 mg/day) also significantly stimulated carnitine accumulation by the epididymis to a level above that of the castrated controls. Simultaneous injection of both cyproterone acetate and testosterone propionate to castrated animals caused an additive effect of these steroids. This indicated that cyproterone acetate in this system is working as a weak androgen. Treatment of rats with 17beta-oestradiol valerate also reduced carnitine accumulation by the cauda epididymis. This is due to suppression of pituiatry gonadotrophin secretion, since concommitant treatment with testosterone propionate (500 mug/day) caused a normalization of the carnitine uptake. Treatment of intact rats with cyproterone acetate significantly reduced the epididymal weight, but not the carnitine accumulation. 17alpha-Hydroxyprogesterone treatment had no effect either on the epididymal weight or the accumulation of the carnitine. Unilateral orchiectomy reduced the carnitine accumulation by the cauda epididymis to about 40% of that occurring in the non-operated control side. This indicates that the luminal contact between the testis and epididymis or the luminal content of the epididymis itself is of importance for the androgen-dependent metabolic process occurring in the cauda epididymis. Castration or hormone treatment did not change the conversion of butyrobetaine to carnitine, or the carnitine uptake by heart. Carnitine uptake by the testis after [3H]butyrobetaine injection was rather low and this would exclude the possibility of synthesis of carnitine in the testis as a source of epididymal carnitine. Carnitine only accumulated in the cauda epididymis in vivo 4 to 96 h after injection of [3H]butyrobetaine. The presence of radioactively labeled butyrobetaine or methylcholine was not detected.

Animals↗

PubMed2002

Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives.

OBJECTIVE: To compare the effects of cyproterone acetate and desogestrel, as part of combined oral contraceptives, on lipid metabolism and hirsutism of adolescents with polycystic ovary syndrome (PCOS). DESIGN: Prospective randomized clinical trial. SETTING: Outpatient gynecology clinic (referral center) of a university. PATIENT(S): Twenty-eight adolescent girls with clinical and biological hyperandrogenism and six or less menses during the past 12 months. INTERVENTION(S): Group A (n = 14) received 0.15 mg of desogestrel plus 0.030 mg of ethinyl estradiol daily. Group B (n = 14) received 2 mg of cyproterone acetate plus 0.035 mg of ethinyl estradiol daily. Treatment was given for 21 days followed by a 7-day rest for a period of 12 months. MAIN OUTCOME MEASURE(S): Hirsutism and lipid profile were evaluated before initiation and at 3, 6, 9, and 12 months of treatment. Androgen profile was evaluated before and at 12 months of treatment. RESULT(S): A significant decline of the Ferriman-Gallway hirsutism score was observed from the sixth month of therapy in both groups. During therapy, the levels of testosterone, free testosterone, Delta(4)-androstenedione, and 17OH-progesterone decreased significantly, whereas sex hormone-binding globulin (SHBG) increased significantly in both groups. The level of total cholesterol and low density lipoprotein (LDL) cholesterol increased significantly, whereas high density lipoprotein (HDL) cholesterol and apolipoprotein A-I increased significantly from the third month of therapy in both groups. Total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios remained unchanged. The levels of triglycerides increased significantly in the cyproterone acetate-treated group after the third month. CONCLUSION(S): Treatment of adolescent girls with PCOS with the two studied formulations is comparably effective in decreasing hirsutism and androgen levels. Both combined oral contraceptives are associated with an increase of total cholesterol, LDL cholesterol, and HDL cholesterol levels and no change of the total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios. Treatment with the cyproterone acetate combined oral contraceptive is associated with a tendency toward increasing the levels of triglycerides.

Adolescent↗

PubMed2006

Prostate specific antigen expression does not necessarily correlate with prostate cancer cell growth.

PURPOSE: The antiproliferative effects of pharmacological agents used for androgen ablative therapy in prostate cancer, including goserelin, bicalutamide and cyproterone acetate (Fluka Chemie, Buchs, Switzerland), were tested in vitro. It was determined whether they affected prostate specific antigen mRNA and protein expression independent of growth inhibition. MATERIALS AND METHODS: Goserelin, bicalutamide (AstraZeneca, Zug, Switzerland) and cyproterone acetate were added to prostate specific antigen expressing, androgen dependent LNCaP and androgen independent C4-2 cell line (Urocor, Oklahoma City, Oklahoma) cultures. Proliferation was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide assay (Roche, Mannheim, Germany). Prostate specific antigen mRNA expression was assessed by quantitative real-time polymerase chain reaction. Secreted prostate specific antigen protein levels were quantified by microparticle enzyme-immunoassay. RESULTS: Goserelin inhibited cell growth and prostate specific antigen protein secretion in LNCaP and C4-2 cells. Prostate specific antigen mRNA expression was not decreased. Bicalutamide did not affect cell growth or prostate specific antigen mRNA expression in LNCaP or C4-2 cells, although it significantly decreased prostate specific antigen protein secretion in LNCaP and to a lesser extent in C4-2 cells. Cyproterone acetate decreased the growth of C4-2 but not of LNCaP cells. It did not affect prostate specific antigen mRNA or protein expression in either cell line. CONCLUSIONS: Prostate specific antigen expression does not necessarily correlate with cell growth. Without a substantial effect on cell growth bicalutamide lowers prostate specific antigen synthesis, whereas cyproterone acetate decreases cell growth with no effect on prostate specific antigen secretion. Prostate specific antigen expression may be influenced by growth inhibition but also by altered mRNA and protein levels depending on the agent, its concentration and the cell line evaluated. For interpreting clinical trials prostate specific antigen is not necessarily a surrogate end point marker for a treatment effect on prostate cancer cell growth.

Androgen Antagonists↗