BACKGROUND, AIM AND SCOPE: Pollution-induced endocrine disruption in vertebrates and invertebrates is a worldwide environmental problem, but relatively little is known about effects of endocrine disrupting compounds (EDCs) in planktonic crustaceans (including Daphnia magna). Aims of the present study were to investigate acute 48 h toxicity and sub-chronic (4-6 days) and chronic (21 days) effects of selected EDCs in D. magna. We have investigated both traditional endpoints as well as other parameters such as sex determination, maturation, molting or embryogenesis in order to evaluate the sensitivity and possible use of these endpoints in ecological risk assessment. MATERIALS AND METHODS: We have studied effects of four model EDCs (vinclozolin, flutamide, ketoconazole and dicofol) on D. magna using (i) an acute 48 h immobilization assay, (ii) a sub-chronic, 4-6 day assay evaluating development and the sex ratio of neonates, and (iii) a chronic, 21 day assay studying number of neonates, sex of neonates, molting frequency, day of maturation and the growth of maternal organisms. RESULTS: Acute EC50 values in the 48 h immobilization test were as follows (mg/L): dicofol 0.2, ketoconazole 1.5, flutamide 2.7, vinclozolin >3. Short-term, 4-6 day assays with sublethal concentrations showed that the sex ratio in Daphnia was modulated by vinclozolin (decreased number of neonate males at 1 mg/L) and dicofol (increase in males at 0.1 mg/L). Flutamide (up to 1 mg/L) had no effect on the sex of neonates, but inhibited embryonic development at certain stages during chronic assay, resulting in abortions. Ketoconazole had no significant effects on the studied processes up to 1 mg/L. DISCUSSION: Sex ratio modulations by some chemicals (vinclozolin and dicofol) corresponded to the known action of these compounds in vertebrates (i.e. anti-androgenicity and anti-oestrogenicity, respectively). Our study revealed that some chemicals known to affect steroid-regulated processes in vertebrates can also affect sublethal endpoints (e.g. embryonic sex determination and/or reproduction) in invertebrates such as D. magna. CONCLUSIONS: A series of model vertebrate endocrine disrupters affected various sub-chronic and chronic parameters in D. magna including several endpoints that have not been previously studied in detail (such as sex determination in neonates, embryogenesis, molting and maturation). Evaluations of traditional reproduction parameters (obtained from the 21 day chronic assay). as well as the results from a rapid, 4-6 day, sub-chronic assay provide complementary information on non-lethal effects of suspected organic endocrine disrupters. RECOMMENDATIONS AND PERSPECTIVES: It seems that there are analogies between vertebrates and invertebrates in toxicity mechanisms and in vivo effects of endocrine disruptors. However, general physiological status of organisms may also indirectly affect endpoints that are traditionally considered 'hormone regulated' (especially at higher effective concentrations as observed in this study) and these factors should be carefully considered. Further research of D. magna physiology and comparative studies with various EDCs will help to understand mechanisms of action as well as ecological risks of EDCs in the environment.

• MeSH
• chemické látky znečišťující vodu toxicita   MeSH
• Daphnia účinky léků   fyziologie   MeSH
• dikofol toxicita   MeSH
• endokrinní disruptory toxicita   MeSH
• flutamid toxicita   MeSH
• ketokonazol toxicita   MeSH
• lokomoce účinky léků   MeSH
• novorozená zvířata MeSH
• oxazoly toxicita   MeSH
• pohlavní dospělost účinky léků   MeSH
• poměr pohlaví MeSH
• rozmnožování účinky léků   MeSH
• shazování tělního pokryvu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemické látky znečišťující vodu MeSH
• dikofol MeSH
• endokrinní disruptory MeSH
• flutamid MeSH
• ketokonazol MeSH
• oxazoly MeSH
• vinclozolin MeSH Prohlížeč

• MeSH
• flutamid terapeutické užití   MeSH
• hirzutismus farmakoterapie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• flutamid MeSH

• MeSH
• anilidy terapeutické užití   MeSH
• flutamid terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty farmakoterapie   patologie   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• anilidy MeSH
• flutamid MeSH

The authors evaluate the effects of 2 months of treatment with 250 mg flutamide daily on adrenal steroidogenesis (ACTH test) and metabolic parameters (lipids, insulin resistance) in 12 PCOS women aged 33.8 +/- 7.5 years and with a BMI of 33.6 +/- 4.2 kg/m2. Significant decreases in basal DHEA-S (p < 0.0001), DHEA (p < 0.01) and androstenedione (p < 0.05), in the ACTH-stimulated levels of DHEA-S (p < 0.0001), testosterone (p < 0.05) and in ACTH-stimulated 17beta-hydroxysteroid dehydrogenase activity (p < 0.01) were observed. No significant change in basal blood glucose, insulin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides or in insulin resistance, as estimated by the insulin tolerance test, was found. Flutamide is effective in reducing adrenal androgen production in overweight women, but has no effect on lipid spectrum or on insulin resistance.

• MeSH
• 17-hydroxysteroidní dehydrogenasy metabolismus   MeSH
• adrenokortikotropní hormon MeSH
• androgeny biosyntéza   MeSH
• androstendion krev   MeSH
• antagonisté androgenů farmakologie   MeSH
• dehydroepiandrosteron krev   MeSH
• dehydroepiandrosteronsulfát krev   MeSH
• dospělí MeSH
• flutamid farmakologie   MeSH
• index tělesné hmotnosti MeSH
• inzulin metabolismus   MeSH
• inzulinová rezistence MeSH
• lidé MeSH
• lipidy krev   MeSH
• nadledviny účinky léků   metabolismus   MeSH
• obezita komplikace   metabolismus   MeSH
• sekrece inzulinu MeSH
• steroidy biosyntéza   MeSH
• syndrom polycystických ovarií komplikace   metabolismus   MeSH
• testosteron krev   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 17-hydroxysteroidní dehydrogenasy MeSH
• adrenokortikotropní hormon MeSH
• androgeny MeSH
• androstendion MeSH
• antagonisté androgenů MeSH
• dehydroepiandrosteron MeSH
• dehydroepiandrosteronsulfát MeSH
• flutamid MeSH
• inzulin MeSH
• lipidy MeSH
• steroidy MeSH
• testosteron MeSH

Vinclozolin (VZ) is a pesticide that acts as an anti-androgen to impair reproduction in mammals. However, VZ-induced disruption of reproduction is largely unknown in fish. In the present study, we have established a combination exposure in which adult goldfish were exposed to VZ (30 and 100 μg/L), anti-androgen flutamide (Flu, 300 μg/L), and androgen testosterone (T, 1 μg/L) to better understand effects of VZ on reproductive endocrine system. mRNA levels of kisspeptin (kiss-1 and kiss-2) and its receptor (gpr54), salmon gonadotropin-releasing hormone (gnrh3) and androgen receptor (ar) in the mid-brain, and luteinizing hormone receptor (lhr) in the testis were analyzed and compared with those of control following 10 days of exposure. kiss-1 mRNA level was increased in goldfish exposed to 100 µg/L VZ and to Flu, while kiss-2 mRNA level was increased following exposure to Flu and to combinations of 30 µg/L VZ with Flu, 100 µg/L VZ with T, and Flu with T. gpr54 mRNA level was increased in goldfish exposed to Flu and to combination of 30 µg/L VZ with Flu and 100 µg/L VZ with T. gnrh3 mRNA level was increased in goldfish exposed to 100 µg/L VZ, to Flu, and to combinations of 30 µg/L VZ with Flu, 100 µg/L VZ with T, and Flu with T. The mid-brain ar mRNA level was increased in goldfish exposed to Flu and to combinations of 30 µg/L VZ with Flu, 100 µg/L VZ with T, and Flu with T. Testicular lhr mRNA level was increased in goldfish exposed to Flu and to combination of 30 µg/L VZ with Flu. These results suggest that VZ and Flu are capable of interfering with kisspeptin and GnRH systems to alter pituitary and testicular horonal functions in adult goldfish and the brain ar mediates VZ-induced disruption of androgen production.

• Klíčová slova
• Androgen receptor, Flutamide, Kisspeptin, Luteinizing hormone receptor, Salmon gonadotropin-releasing hormone, Testosterone,
• MeSH
• androgenní receptory genetika   MeSH
• androgeny farmakologie   MeSH
• antagonisté androgenů farmakologie   MeSH
• flutamid farmakologie   MeSH
• hormon uvolňující gonadotropiny genetika   MeSH
• karas zlatý genetika   MeSH
• kisspeptiny genetika   MeSH
• kyselina pyrrolidonkarboxylová analogy a deriváty   MeSH
• lékové interakce MeSH
• messenger RNA metabolismus   MeSH
• mozek účinky léků   metabolismus   MeSH
• oxazoly farmakologie   MeSH
• průmyslové fungicidy farmakologie   MeSH
• receptory LH genetika   MeSH
• receptory spřažené s G-proteiny genetika   MeSH
• rozmnožování účinky léků   MeSH
• rybí proteiny genetika   MeSH
• testis účinky léků   metabolismus   MeSH
• testosteron farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• androgenní receptory MeSH
• androgeny MeSH
• antagonisté androgenů MeSH
• flutamid MeSH
• gonadotropin-releasing hormone-III MeSH Prohlížeč
• hormon uvolňující gonadotropiny MeSH
• kisspeptiny MeSH
• kyselina pyrrolidonkarboxylová MeSH
• messenger RNA MeSH
• oxazoly MeSH
• průmyslové fungicidy MeSH
• receptory LH MeSH
• receptory spřažené s G-proteiny MeSH
• rybí proteiny MeSH
• testosteron MeSH
• vinclozolin MeSH Prohlížeč

The antirenotropic activities of three antiandrogens which are frequently used in the clinical praxis (cyproterone acetate, flutamide and casodex) and of natural endogenous antiandrogen epitestosterone were compared. The substances were administered in oil intraperitoneally to intact male mice. The weight of kidneys was decreased most effectively by casodex and epitestosterone, though the antiandrogenic activity expressed by the decreased weight of seminal vesicles was confirmed in all preparation tested, except for flutamide. Only epitestosterone significantly reduced the level of plasma testosterone, whereas casodex increased testosterone level in plasma. LH level was decreased by testosterone propionate and epitestosterone significantly, but about 50 percent increase in the mean LH level in casodex treated animals did not reach the statistical significance.

• Publikační typ
• časopisecké články MeSH

Combined androgen blockade using surgical or medical (luteinizing hormone-releasing hormone agonist) castration in association with anti-androgen has become the primary therapy in patients with metastatic prostate cancer. Patients undergoing combined androgen blockade will progress within 18-30 months after initial hormonal therapy. When progression occurs following combined androgen blockade, the non-steroid anti-androgen should be subsequently withdrawn. Several recent reports have been published on the paradoxical effect of anti-androgen withdrawal. Eight (22.9%) of 35 patients showed a decline in PSA levels following flutamide withdrawal. The mean time to progression following combined androgen blockade was 26 month and the mean duration of response to flutamide withdrawal was 4.1 months.

• MeSH
• antagonisté androgenů aplikace a dávkování   MeSH
• flutamid aplikace a dávkování   MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty imunologie   terapie   MeSH
• orchiektomie MeSH
• prostatický specifický antigen krev   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• antagonisté androgenů MeSH
• flutamid MeSH
• prostatický specifický antigen MeSH

Recently it has been shown that vitamin D(3) acting via its cognate receptor (VDR) regulates the growth, differentiation and function of female reproductive tissues including ovary. The aim of the study was to examine the effect of testosterone (T) and its antagonist 2-hydroxyflutamide (HF) on VDR protein expression and function in porcine ovarian follicles. Medium size antral follicles expressing great amount of androgen receptors and represent high steroidogenic activity were used in this research. After 6 h incubation of whole follicles with T, HF or T+HF, immunohistochemical analysis of VDR revealed its nuclear localization in granulosa and theca interna cells in control and experimental groups. The expression of VDR protein was shown as a band of 48 kDa. There were no significant differences between either experimental group and the control. T influenced the function of VDR through decreased formation of VDR/RXR (retinoid X receptor) complexes (P<0.05) in both granulosa and theca interna cells, but HF abolished this effect only in granulosa cells (P<0.05). These results suggest that androgens regulate the response of follicular cells to vitamin D3 in pigs ovary via regulation of VDR transcriptional activity.

• MeSH
• flutamid analogy a deriváty   MeSH
• ovariální folikul metabolismus   MeSH
• prasata MeSH
• receptory kalcitriolu metabolismus   MeSH
• techniky in vitro MeSH
• testosteron fyziologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• flutamid MeSH
• hydroxyflutamide MeSH Prohlížeč
• receptory kalcitriolu MeSH
• testosteron MeSH

Young intact and adult castrated outbred C3H/Di male mice were used to characterize steroid hormone agonist and antagonist activities of anti-androgens by bioassay. Animals were injected subcutaneously with flutamide (Flut), chlormadinone acetate (CMA), cyproterone acetate (CA) or Casodex (Cas) alone or simultaneously with oestradiol (E), E plus progesterone (Prog) or norethindrone acetate (NA; a steroid exhibiting progestational and oestrogenic activities) and testosterone (T) for 15 days. Mammary gland growth was not affected with anti-androgen alone. However, all anti-androgens decreased seminal vesicle weights in intact males. In E (0.01 microg day(-1))-treated intact males, mammary growth was stimulated by CMA (progestational activity) and inhibited by CA. The inhibitory effect of CA on mammary growth (glucocorticoid activity) was overcome with high dose of E (0.1 microg day(-1)). When seminal vesicles weights were decreased with a moderate dose of E (0.01 microg day(-1)) anti-androgens injected simultaneously acted synergistically with E and decreased seminal vesicles weights more than E alone. However, in animals overloaded with E (0.1 microg day(-1)), anti-androgen CA was unable to decrease seminal vesicles weights. E (0.01 or 0.05 microg day(-1)) or E + Prog (500 or 1000 microg day(-1)) or NA (12.5 to 50 microg day(-1)) stimulated mammary growth was inhibited by T at doses 20-200 microg day(-1) and these effects were decreased or abolished by simultaneous application of Flut, CMA or Cas in both young intact and adult castrated males. In the same animals, the seminal vesicles weights were increased by T and decreased by anti-androgens. The effects of higher doses of T (300 microg day(-1)) were not inhibited by anti-androgens both in the mammary gland and seminal vesicles. Spleen weights were not consistently affected with Flut, CMA or Cas, but decreased with CA by dose dependent manner. These results demonstrated that anti-androgenic activities could be detected not only on seminal vesicle but also on the mammary gland. Our model system also detected a glucocorticoid activity of CA and progestational activity of CMA.

• MeSH
• anilidy farmakologie   MeSH
• antagonisté androgenů farmakologie   MeSH
• biotest MeSH
• chlormadinon farmakologie   MeSH
• cyproteronacetát farmakologie   MeSH
• estradiol farmakologie   MeSH
• flutamid farmakologie   MeSH
• kombinovaná farmakoterapie MeSH
• mléčné žlázy zvířat účinky léků   MeSH
• myši inbrední C3H MeSH
• myši MeSH
• nitrily MeSH
• norethindron analogy a deriváty   farmakologie   MeSH
• norethisteron acetát MeSH
• orchiektomie MeSH
• outbrední kmeny zvířat MeSH
• progesteron farmakologie   MeSH
• semenné váčky účinky léků   MeSH
• slezina účinky léků   MeSH
• steroidy farmakologie   MeSH
• tosylové sloučeniny MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anilidy MeSH
• antagonisté androgenů MeSH
• bicalutamide MeSH Prohlížeč
• chlormadinon MeSH
• cyproteronacetát MeSH
• estradiol MeSH
• flutamid MeSH
• nitrily MeSH
• norethindron MeSH
• norethisteron acetát MeSH
• progesteron MeSH
• steroidy MeSH
• tosylové sloučeniny MeSH

• Klíčová slova
• combined hormonal contraceptive, flutamide, genetic, metformin, polycystic ovary syndrome,
• Publikační typ
• časopisecké články MeSH