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1.
Artigo em Inglês | MEDLINE | ID: mdl-32109748

RESUMO

The standard approach to detect misuse with testosterone in sport is based on the determination and evaluation of the urinary steroid profile followed by the confirmation of atypical profiles using isotope ratio mass spectrometry. The detection capacity of these methods can be attenuated by confounding factors or testosterone preparations with endogenous isotopic fingerprints. An alternative detection method for misuse of an endogenous steroid in sports is the direct detection of the administered steroid ester present in most preparations. Thus unambiguous proof for doping misuse can be delivered. In this work, the sensitivity of gas chromatography coupled to a triple quadrupole with chemical ionization (GC-CI-MS/MS) is applied to detect trace levels of 10 testosterone and 2 nandrolone esters in plasma for in human doping analysis. The detection method was developed employing a liquid-liquid extraction and HPLC cleanup step before analysis on the GC-CI-MS/MS. The quantitative method was validated in a linear range of 100-2000 pg/ml and proved to be selective, reproducible and very sensitive with limits of detection as low as to 10 pg/ml. A clinical study with the administration of testosterone undecanoate in 3 volunteers was carried out and the compound was detectable up to 86 days after administration.


Assuntos
Doping nos Esportes , Cromatografia Gasosa-Espectrometria de Massas/métodos , Esteroides/sangue , Espectrometria de Massas em Tandem/métodos , Ésteres , Humanos , Modelos Lineares , Extração Líquido-Líquido , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Esteroides/química , Esteroides/isolamento & purificação , Testosterona/análogos & derivados , Testosterona/sangue
2.
PLoS One ; 15(2): e0229391, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32092110

RESUMO

Our previous work documented significant advancements in steroid-induced progression of oogenesis, demonstrating that co-treatment of female eels with 11-ketotestosterone (11KT) and estradiol-17ß (E2) successfully induced uptake of vitellogenin by oocytes. Here we evaluate the effects of this steroid co-treatment on subsequent time to ovulation and egg quality in shortfinned eels artificially matured by hypophysation. Co-treatment with 11KT (1 mg) and E2 (0.2 or 2 mg) significantly reduced time to ovulation and therefore, the amount of pituitary homogenate required, without any detrimental effects on gonadosomatic index, oocyte diameter or the total weight of stripped eggs. E2 treatment resulted in promising increases in fertilization rates. These indicators suggest that co-treatment with 11KT and E2 holds promise for future artificial maturation practices in terms of minimising fish handling and stress, and of reducing the need for expensive pituitary preparations.


Assuntos
Anguilla , Estradiol/farmacologia , Oogênese/efeitos dos fármacos , Indução da Ovulação , Testosterona/análogos & derivados , Anguilla/fisiologia , Animais , Feminino , Fertilidade/efeitos dos fármacos , Oócitos/citologia , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Oogênese/fisiologia , Ovário/citologia , Ovário/efeitos dos fármacos , Indução da Ovulação/métodos , Indução da Ovulação/veterinária , Testosterona/farmacologia
3.
J Urol ; 203(5): 940-948, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31845837

RESUMO

PURPOSE: Beyond testosterone, several steroids contribute to the activation of the androgen receptor pathway, but their relative contributions to the activation of the androgen receptor signaling axis in patients with castrated prostate cancer remain unknown. MATERIALS AND METHODS: Serum levels of 9 steroids were measured by mass spectrometry from continuously castrated patients of the PR.7 study (219) and from the PCA24 cohort (116). For each steroid standard curves for dose dependent prostate specific antigen promoter activation were built in castration sensitive (LAPC4) and resistant (VCaP) prostate cancer models. Standard curves were used to determine the androgen receptor activation potency for each steroid measurement from patients in these trials. RESULTS: In LAPC4 and VCaP cells testosterone, dihydrotestosterone and androstenedione induced androgen receptor transcriptional activity, while dehydroepiandrosterone, 5alpha-androstan-3beta,17beta-diol, androstenediol and androsterone stimulated androgen receptor only in VCaP cells. Extragonadal steroids were responsible for 34% (LAPC4) and 88% (VCaP) of the serum total androgen receptor transcriptional activity found in castrated cases. The total androgen receptor transcriptional activity secondary to testosterone, dihydrotestosterone and androstenedione was associated with time to castration resistance in patients from the PR.7 study (HR 2.17, 95% CI 1.12-4.23, p=0.02) in multivariate analysis using the castration sensitive model (LAPC4). Androgen receptor transcriptional activity of extragonadal androstenedione was the only steroid statistically associated with time to castration resistance in univariate analysis (HR 1.89, 95% CI 1.04-3.44, p=0.036). CONCLUSIONS: Extragonadal steroids contribute significantly to the androgen receptor axis activation at castration levels of testosterone in recurrent nonmetastatic prostate cancer and these sustain the development of castration resistance after primary local treatment.


Assuntos
Androstenodiona/farmacologia , Castração/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/terapia , Receptores Androgênicos/metabolismo , Testosterona/análogos & derivados , Testosterona/farmacologia , Anabolizantes/farmacologia , Androgênios/farmacologia , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Seguimentos , Humanos , Masculino , Espectrometria de Massas , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Próstata/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/efeitos dos fármacos , Fatores de Tempo
4.
Chemosphere ; 240: 124900, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31563099

RESUMO

Spirotetramat (SPT) is a new tetronic acid derivative insecticide used to control scales and aphids; the potential for endocrine disruptor effects in fish could not be finalized with the available data. In this study, zebrafish were selected to assess the endocrine-disrupting effects. Significant decrease of plasma estradiol (E2), testosterone (T) and 11-ketotestosterone (11-KT) were observed in both male and female following the spirotetramat exposure; the vitellogenin (VTG) level in females significantly decreased. The expression of the hypothalamic-pituitary-gonad (HPG) axis genes fshr, lhr and esr1 showed significant increase in the gonads, which expression in males is higher than in females. In addition, the activities of capspase-3 and caspase-9 significantly decreased in both males and females liver, while the capspase-3 and caspase-9 were increased in male testis, the mRNA expression levels of genes expression related to the apoptosis pathway were also significantly altered after the spirotetramat exposure. Additionally, we found the parental zebrafish exposed to spirotetramat induced the development delay of its offspring. Above all, the adverse effects induced by spirotetramat suggesting that spirotetramat is a potential exogenous hazardous agent.


Assuntos
Compostos Aza/toxicidade , Inseticidas/toxicidade , Compostos de Espiro/toxicidade , Animais , Apoptose , Disruptores Endócrinos/toxicidade , Estradiol/metabolismo , Estrogênios/farmacologia , Feminino , Expressão Gênica , Gônadas/efeitos dos fármacos , Fígado/metabolismo , Masculino , Testículo/efeitos dos fármacos , Testosterona/análogos & derivados , Vitelogeninas/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo
5.
Gen Comp Endocrinol ; 285: 113241, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400434

RESUMO

Pituitary gonadotropins, follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh), play central roles in the control of gonadal development of vertebrates. In mammals, Fsh and Lh exclusively activate their respective cognate receptors: Fsh receptor (Fshr) in the Sertoli cell and Lh/choriogonadotropin receptor (Lhcgr) in the Leydig cell. In teleosts, the distinct functions of Fsh and Lh and information on cellular localization of their receptors are still poorly understood. Recently we established FreeStyle 293-F cell lines producing recombinant Japanese eel Fsh and Lh (reFsh and reLh), which form a single chain consisting of a common α-subunit and ß-subunits. In this study, we conducted functional analyses of reFsh and reLh, focusing on the binding specificities to their receptors and effects on testicular steroidogenesis in vitro. Assays with gonadotropin receptors-expressing COS-7 cells indicated reFsh stimulated its cognate receptor, meanwhile reLh activated both receptors. Although results of in vitro incubations showed that reFsh and reLh induced testicular 11-ketotestosterone production in a dose and time-dependent manner by upregulating expression of steroidogenic enzymes, the effective doses of reLh were apparently lower and the effects of reLh emerged faster in comparison with reFsh. Results of quantitative real-time PCR using testicular cell fractions showed that fshr and lhcgr1 mRNA were detected both in Sertoli and Leydig cells. These analyses revealed that reFsh and reLh were biologically active and hence will be useful for future studies. Moreover, our data showed that both eel Fsh and Lh acted as steroidogenic hormones through their receptors in testicular somatic cells; however, Lh was more potent on androgen production, implying differential functions on spermatogenesis.


Assuntos
Anguilla/metabolismo , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Receptores do FSH/metabolismo , Receptores do LH/metabolismo , Proteínas Recombinantes/metabolismo , Esteroides/metabolismo , Testículo/metabolismo , Animais , Células COS , Linhagem Celular , Chlorocebus aethiops , Cicloeximida/farmacologia , Dactinomicina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Japão , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores do FSH/genética , Receptores do LH/genética , Testosterona/análogos & derivados , Testosterona/metabolismo
6.
Aquat Toxicol ; 217: 105327, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31703940

RESUMO

Numerous anthropogenic sources, such as pulp mill and sewage treatment effluents, contain androgenic endocrine disrupting compounds that alter the reproductive status of aquatic organisms. The current study injected adult male mummichog (Fundulus heteroclitus) with 0 (control), 1 pg/g, 1 ng/g or 1 µg/g body weight of the model androgen 5α-dihydrotestosterone (DHT) with the intent to induce a period of plasma sex hormone depression, a previously-observed effect of DHT in fish. A suite of gonadal steroidogenic genes were assessed during sex hormone depression and recovery. Fish were sampled 6, 12, 16, 18, 24, 30 and 36 h post-injection, and sections of testis tissue were either snap frozen immediately or incubated for 24 h at 18 °C to determine in vitro gonadal hormone production and then frozen. Plasma testosterone (T) and 11-ketotestosterone (11KT) were depressed beginning 24 h post-injection. At 36 h post-injection plasma T remained depressed while plasma 11KT had recovered. In snap frozen tissue there was a correlation between plasma sex hormone depression and downregulation of key steroidogenic genes including steroidogenic acute regulatory protein (star), cytochrome P450 17a1 (cyp17a1), 3ß-hydroxysteroid dehydrogenase (3ßhsd), 11ß-hydroxysteroid dehydrogenase (11ßhsd) and 17ß-hydroxysteroid dehydrogenase (17ßhsd). Similar to previous studies, 3ßhsd was the first and most responsive gene during DHT exposure. Gene responses from in vitro tissue were more variable and included the upregulation of 3ßhsd, 11ßhsd and star during the period of hormone depression. The differential expression of steroidogenic genes from the in vitro testes compared to the snap frozen tissues may be due to the lack of regulators from the hypothalamo-pituitary-gonadal axis present in whole-animal systems. Due to these findings it is recommended to use snap frozen tissue, not post-incubation tissue from in vitro analysis, for gonadal steroidogenic gene expression to more accurately reflect in vivo responses.


Assuntos
Di-Hidrotestosterona/toxicidade , Fundulidae/fisiologia , 17-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Di-Hidrotestosterona/sangue , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Gônadas/efeitos dos fármacos , Masculino , Fosfoproteínas/metabolismo , Reprodução/efeitos dos fármacos , Esteroide 17-alfa-Hidroxilase/metabolismo , Testículo/efeitos dos fármacos , Testosterona/análogos & derivados , Testosterona/metabolismo , Poluentes Químicos da Água/toxicidade
7.
Mar Pollut Bull ; 145: 418-428, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31590805

RESUMO

Pollution threats Antarctica and scientists blame xenobiotics and anthropic activities. Yet little is known about their effect on Antarctic ichthyofauna. Accordingly, we investigated the endocrine system of male fish Notothenia rossii and N. coriiceps (Perciformes, Nototheniidae) collected during Austral summer. For N. rossii, hormone levels of estradiol, testosterone, and 11-ketotestosterone were higher in fish collected during March than those of January; whereas for N. coriiceps estradiol and androgens levels were higher and lower in March, respectively. Histological analysis of the testes showed an unrestricted lobular type with no pathological alterations. However, detection of vitellogenin-like in plasma and skin mucus were seen in 75% of N. coriiceps males and 7% of N. rossii males. This is the first report of mucus vitellogenin-like detection as a non-invasive biomarker of endocrine disruption in notothenioid males and settles a baseline for future studies of reproductive biology and endocrine disruption in Antarctic fishes.


Assuntos
Sistema Endócrino/metabolismo , Perciformes/fisiologia , Reprodução/efeitos dos fármacos , Poluentes da Água/toxicidade , Animais , Regiões Antárticas , Ecotoxicologia , Sistema Endócrino/efeitos dos fármacos , Monitoramento Ambiental , Estradiol/metabolismo , Feminino , Masculino , Perciformes/crescimento & desenvolvimento , Testosterona/análogos & derivados , Testosterona/metabolismo
8.
Forensic Sci Int ; 303: 109925, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31499423

RESUMO

A 34-year old male was found breathless and panting at home by his girlfriend three hours after a gym workout. Minutes later, he collapsed and died. Autopsy, histological and chemical analyses were conducted. The examination of the heart showed left ventricular hypertrophy, while the right coronary artery showed only a small vascular lumen (3 mm in diameter), due to its anatomical structure. In femoral blood concentrations of approx. 1 µg/L clenbuterol, approx. 56 µg/L stanozolol and approx. 8 µg/L metandienone, with trenbolone (

Assuntos
Anabolizantes/efeitos adversos , Clembuterol/efeitos adversos , Doping nos Esportes , Metandrostenolona/efeitos adversos , Estanozolol/efeitos adversos , Adulto , Anabolizantes/análise , Androstanóis/urina , Clembuterol/análise , Clomifeno/urina , Vasos Coronários/patologia , Evolução Fatal , Insuficiência Cardíaca/induzido quimicamente , Humanos , Hipertrofia Ventricular Esquerda/patologia , Masculino , Metandrostenolona/análise , Estanozolol/análise , Testosterona/análogos & derivados , Testosterona/urina , Acetato de Trembolona/sangue , Acetato de Trembolona/urina
9.
Behav Processes ; 167: 103916, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31386887

RESUMO

Male mate discrimination may be affected by the social environment (presence or absence of rival males or mates), which can also affect stress and sex hormones (e.g., cortisol and 11-ketotestosterone (11-KT)). The Amazon molly, Poecilia formosa, is an all-female fish species dependent on sperm from mating with male P. latipinna. We investigated male mate choice in P. latipinna between conspecific females and P. formosa with a rival male present and no rival male present. We measured cortisol and 11-KT release rates from all fish. The presence of a rival male had no effect on male mate choice for conspecific females nor overall mating effort. Male 11-KT decreased on the second day after exposure to a rival male on the first day. Focal male 11-KT is positively correlated with the size of the rival male. Both conspecific and heterospecific females released more 11-KT when in the rival male treatment than when not. Neither male nor female cortisol was affected by the presence or absence of the rival male. We did not find an effect of rival males on male mate choice in contrast to our prediction. Instead, our findings may indicate a hormonal response to social competition.


Assuntos
Hidrocortisona/análise , Preferência de Acasalamento Animal/fisiologia , Testosterona/análogos & derivados , Animais , Feminino , Masculino , Poecilia/fisiologia , Reprodução , Espermatozoides/fisiologia , Testosterona/análise , Água/química
10.
Artigo em Inglês | MEDLINE | ID: mdl-31386905

RESUMO

Gonadotropin-releasing hormones (GnRH) regulate gonadal growth of teleosts. Benzo(a)pyrene (BaP) functions as a reproductive endocrine disruptor. Furthermore, endocrine regulation on brood pouch growth of Syngnathidaes is elusive. To better understand the role of GnRH in brood pouch growth and effects of BaP on reproductive endocrine in lined seahorse (Hippocampus erectus), gnrh2 and gnrh3 genes were identified. Results showed that lined seahorse GnRH2 and GnRH3 precursors included the conservative tripartite structure and their transcripts highly expressed in brain as other teleosts. Expression profiles of gnrh2 and gnrh3 transcripts were detected during brood pouch growth. Results indicated that brain gnrh2 transcripts remarkably increased at the middle-stage and late-stage of brood pouch growth, while brain gnrh3 transcripts significantly raised at the early-stage and middle-stage. These suggested that GnRH2 and GnRH3 regulated brood pouch growth at different stages. Short-term BaP exposure in lined seahorse was performed. Transcripts of gnrh2 and gnrh3 remarkably increased in females and males exposed to BaP. Besides, plasma 17-beta estradiol (E2) levels presented a reduced trend during female fish exposed to BaP. This revealed that BaP functioned as anti-estrogenic effects and it may result in high expression of gnrh mRNA. However, plasma 11-ketone testosterone (11-KT) levels showed an increased trend during male fish exposed to BaP. Taken together, these indicated interesting results of BaP on reproduction in each sex of seahorse. These observations contribute to provide novel information of regulation on brood pouch growth and effects of BaP on reproductive endocrine in Syngnathidaes.


Assuntos
Benzo(a)pireno/farmacologia , Estradiol/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Gônadas/metabolismo , Ácido Pirrolidonocarboxílico/análogos & derivados , Smegmamorpha/metabolismo , Testosterona/análogos & derivados , Animais , Feminino , Masculino , Ácido Pirrolidonocarboxílico/metabolismo , RNA Mensageiro/metabolismo , Reprodução/fisiologia , Testosterona/metabolismo
11.
Gen Comp Endocrinol ; 283: 113227, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31348956

RESUMO

Water temperature is a critical external factor influencing gonadal development in fish. This research aimed to study the impact of elevated temperature on testicular germ cell survival and reproductive capacity of Nile tilapia. Male Nile tilapia were exposed to high temperatures of either 36 (HT1) or 37 °C (HT2) for 3000 degree-days (DD) and thereafter returned to the control temperature of 27 °C (CT) for 2200 DD. The deleterious effects on testicular germ and somatic cells were observed histologically, characterised by vacuolisation, atrophy and the loss of spermatogenic cells in testes with a more severe impact of HT2 compared to HT1. Interestingly, serum 11-ketotestosterone (11-KT) and testosterone (T) levels tended to be higher during the heat treatments than CT. Expression levels of germline-specific genes piwil1, piwil2 and nanos2 and Bcl-2 family genes, bcl-xLb and baxa were significantly reduced during the heat treatment compared to CT, more so in the HT2, while the levels of nanos3 and gfra1 transcripts were only significantly reduced in HT2, implying a significant loss of spermatogonial stem cell (SSC) and spermatogonia in HT2. The effect of HT2 is further evidenced by the significantly reduced sperm density and fertilisation rate compared to CT and HT1 at the end of the recovery period but complete sterility was not induced by HT2. Overall, the present study showed significant effects of HT2 on germ cell survival with histological changes in testes, reduced milt quality, increased 11-KT, and decreased expression of germline-specific genes, SSC marker genes and Bcl-2 family genes in testes which could therefore be potential target genes for sterilisation by genome editing.


Assuntos
Ciclídeos/metabolismo , Espermatozoides/citologia , Temperatura , Testículo/citologia , Testículo/metabolismo , Animais , Ciclídeos/sangue , Ciclídeos/genética , Regulação da Expressão Gênica , Hormônios Esteroides Gonadais/sangue , Masculino , Espermatozoides/ultraestrutura , Testosterona/análogos & derivados , Testosterona/sangue
12.
Theriogenology ; 138: 47-51, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31284221

RESUMO

To test the hypothesis that postnatal sexual steroids induce an impairment of domestic male cat reproductive function, this study describes the physical, endocrine, steroidogenical and histological effects of a single, high dose of a postnatal sexual steroid in this species. Twenty male kittens were randomly assigned within the first 24 h of birth to: Testosterone enanthate 12.5 mg sc (TE; n = 8), medroxyprogesterone acetate 10 mg sc (MA; n = 6), or Placebo sc (PL; n = 6). The cats were followed until puberty when they were castrated. Kittens achieved puberty without age differences among groups (P > 0.05). Two MA cats presented abnormal testicular descent. Histological evaluation of the MA (P < 0.01), but not of TE testes revealed decreased diameter (P < 0.01) and epithelial height (P < 0.01) of the seminiferous tubules. Leydig cell nuclear area was also reduced in this group. Conversely, tubular/intertubular ratio was increased in TE animals (P < 0.01). Quantitative real-time PCR analysis of mRNA expression of testicular tissue revealed no significant differences among groups for StAR, CYP17A1 and androgen receptors. TE animals showed decreased CYP19A1 mRNA expression (P < 0.05). In the first 4 postnatal weeks, fecal testosterone (T) values were high, basal and intermediate in TE, MA and PL (P < 0.05), respectively. These differences progressively diminished and the three groups presented basal T concentrations from the 7th week on (P > 0.05). It was concluded that the postnatal progestagen initially suppressed the gonadal axis and caused an impairment of spermatogenesis and testicular descent at puberty. Androgen treatment caused downregulation of the final steroidogenic cascade.


Assuntos
Disruptores Endócrinos/farmacologia , Reprodução/efeitos dos fármacos , Esteroides/farmacologia , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Testosterona/análogos & derivados , Animais , Animais Recém-Nascidos , Constituição Corporal/efeitos dos fármacos , Gatos , Anticoncepção/métodos , Anticoncepção/veterinária , Hormônios Esteroides Gonadais/farmacologia , Masculino , Reprodução/fisiologia , Maturidade Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testosterona/farmacologia
13.
Endocrinology ; 160(10): 2395-2400, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31199478

RESUMO

Hormone assay results below the assay detection limit (DL) can introduce bias into quantitative analysis. Although complex maximum likelihood estimation methods exist, they are not widely used, whereas simple substitution methods are often used ad hoc to replace the undetectable (UD) results with numeric values to facilitate data analysis with the full data set. However, the bias of substitution methods for steroid measurements is not reported. Using a large data set (n = 2896) of serum testosterone (T), DHT, estradiol (E2) concentrations from healthy men, we created modified data sets with increasing proportions of UD samples (≤40%) to which we applied five different substitution methods (deleting UD samples as missing and substituting UD sample with DL, DL/√2, DL/2, or 0) to calculate univariate descriptive statistics (mean, SD) or bivariate correlations. For all three steroids and for univariate as well as bivariate statistics, bias increased progressively with increasing proportion of UD samples. Bias was worst when UD samples were deleted or substituted with 0 and least when UD samples were substituted with DL/√2, whereas the other methods (DL or DL/2) displayed intermediate bias. Similar findings were replicated in randomly drawn small subsets of 25, 50, and 100. Hence, we propose that in steroid hormone data with ≤40% UD samples, substituting UD with DL/√2 is a simple, versatile, and reasonably accurate method to minimize left censoring bias, allowing for data analysis with the full data set.


Assuntos
Interpretação Estatística de Dados , Estradiol/sangue , Testosterona/análogos & derivados , Testosterona/sangue , Humanos , Limite de Detecção , Masculino , Modelos Estatísticos
14.
J Clin Pharm Ther ; 44(5): 742-749, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31183891

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Thyroid autoimmune diseases occur much more frequently in women than men. Unfortunately, no previous study has determined whether sex hormones produce any effect on thyroid antibody titres. The primary study aim was to assess whether exogenous testosterone affects thyroid autoimmunity in men with Hashimoto's thyroiditis and low testosterone levels. METHODS: The study population consisted of 34 euthyroid men with autoimmune thyroiditis and testosterone deficiency. On the basis of patient preference, these patients were either treated with oral testosterone undecanoate (120 mg daily; n = 16) or remained untreated (n = 18). Circulating levels of thyrotropin, free thyroxine, free triiodothyronine, prolactin and total testosterone, as well as serum titres of thyroid peroxidase and thyroglobulin antibodies, were measured at the beginning of the study and 6 months later. The structure parameters of thyroid homeostasis (Jostel's thyrotropin index, SPINA-GT and SPINA-GD) were also calculated. Moreover, semen analyses were performed in eight patients in each group. RESULTS AND DISCUSSION: In testosterone-naïve men, serum hormone levels and antibody titres remained at the similar levels throughout the study. Apart from increasing serum testosterone levels, testosterone undecanoate reduced titres of thyroid peroxidase and thyroglobulin antibodies and increased SPINA-GT. The drug produced a neutral effect on circulating levels of thyrotropin, free thyroid hormones, prolactin and testosterone, Jostel's thyrotropin index, SPINA-GD and semen parameters. Testosterone-induced changes in antibody titres correlated with the effect of treatment on SPINA-GT and with serum testosterone levels. WHAT IS NEW AND CONCLUSION: This study is the first one to have shown that exogenous testosterone may have a protective effect on thyroid autoimmunity in men with Hashimoto's thyroiditis and testosterone deficiency.


Assuntos
Autoanticorpos/uso terapêutico , Autoimunidade/efeitos dos fármacos , Doença de Hashimoto/tratamento farmacológico , Testosterona/sangue , Testosterona/uso terapêutico , Glândula Tireoide/efeitos dos fármacos , Feminino , Doença de Hashimoto/sangue , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Iodeto Peroxidase/sangue , Masculino , Pessoa de Meia-Idade , Testosterona/análogos & derivados , Tireoglobulina/sangue , Hormônios Tireóideos/sangue , Tireotropina/sangue
15.
Int J Exp Pathol ; 100(3): 192-201, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31131507

RESUMO

Chrysin (5,7-dihydroxyflavone) is a bioactive compound found in different fruits, vegetables, honey and propolis. This flavone has been suggested for the treatment of reproductive dysfunction, mainly because of its antioxidant and hormonal properties. However, the effects of this polyphenol on the prostate are still poorly understood. The purpose of this study was to evaluate the effects of short-term chrysin exposure on the ventral male and female prostates of adult gerbils. To evaluate the androgenic potential of chrysin, gerbils were also exposed to testosterone. Male and female gerbils were exposed to chrysin (50 mg/kg/day, orally) or testosterone cypionate (1 mg/kg/week, subcutaneously) for 3, 7 and 21 days. Prostates were dissected for morphological, stereological and immunohistochemical analyses. Serum levels of testosterone and 17ß-estradiol were measured by ELISA. Serum testosterone levels were not increased by chrysin supplementation in males or females. However, only females treated with chrysin for 21 days showed an increase in estradiol levels. Increased androgen receptor immunoreactivity, higher proliferation rates and glandular hyperplasia were observed in male and female prostates for all chrysin treatment times. Additionally, increased oestrogen receptor alpha immunoreactivity was observed in all chrysin-treated females. Although chrysin and testosterone promoted similar morphological changes in the gerbil prostate, chrysin supplementation was less deleterious to prostate health, since it resulted in lower incidence of hyperplasia and an absence of neoplastic foci.


Assuntos
Flavonoides/farmacologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Próstata/efeitos dos fármacos , Receptores Androgênicos/efeitos dos fármacos , Animais , Disruptores Endócrinos/farmacologia , Feminino , Gerbillinae , Masculino , Gravidez , Testosterona/análogos & derivados , Testosterona/farmacologia , Fatores de Tempo
16.
Aquat Toxicol ; 212: 194-204, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31132737

RESUMO

Gemfibrozil (GEM) is a fibrate lipid regulator and one of the most commonly occurring fresh water pharmaceuticals. The negative effects of fibrates including GEM on fish reproduction have been frequently reported including effects of F0 GEM exposure on reproduction of the unexposed F1 offspring. We predicted that chronic, direct exposure of zebrafish with low concentrations of GEM would adversely affect parental male reproduction and unexposed offspring for multiple generations. Adult zebrafish were exposed to 10 µg/L GEM for 6 weeks and a range of reproductive indices were analyzed. The F1-F4 offspring were reared in clean water from 3 distinct lineages where only a single or both parents were exposed and compared to a control lineage where parents were unexposed. Reproductive indices were examined in unexposed F1-F4 offspring to test the hypothesis of multi- or trans- generational impacts. Exposure to GEM caused a decline in breeding success and mean embryo production in F0 parents and a reduction in whole body 11-ketotestosterone (11-KT), altered male courtship, aggression and sperm morphology. Our results indicate that paternal exposure alone is sufficient to result in reproductive effects in unexposed male offspring but that effects are mostly limited to F1. We suggest that GEM may act as a reproductive endocrine disruptor in fish and that chronic exposure reduced male reproductive fitness but not over multiple generations.


Assuntos
Exposição Ambiental , Genfibrozila/toxicidade , Reprodução/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Feminino , Água Doce , Masculino , Comportamento Sexual Animal/efeitos dos fármacos , Testosterona/análogos & derivados , Testosterona/metabolismo
17.
Gen Comp Endocrinol ; 281: 30-40, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31102580

RESUMO

Steelhead Trout (Oncorhynchus mykiss) display a varied life-history, including precocious male maturation at age-1 or age-2. In wild fish, precocious male maturation represents an important component of a diverse life-history portfolio. In hatchery programs, however, it is undesirable if rearing practices increase rates of early male maturation and reduce numbers of anadromous male adults. Our study aimed to develop endocrine and molecular markers for identifying males at early stages of maturation in the spring (prior to smolt release) and evaluated the potential use of these markers for quantifying early male maturation rates at a hatchery scale. In a laboratory study, Skookumchuck winter-run Steelhead Trout were reared at a high growth rate in order to increase the occurrence of precocious male maturation. Fish were lethally sub-sampled in February, prior to the time of smolt release; in May, at the time of smolt release; and in September, when 1+ age maturing males that would spawn the following spring were clearly identifiable based solely on gonadosomatic index (GSI). In February and May samples, we measured GSI, plasma 11-ketotestosterone (11KT), mRNAs for pituitary follicle stimulating hormone (fshb) and luteinizing hormone (lhb) beta subunits, and analyzed stage of spermatogenesis by testis histology. Additionally, in May, we measured testis anti-Müllerian hormone (amh) and insulin-like growth factor 3 (igf3) mRNA. Our primary goal was to evaluate the aforementioned maturation indices for their efficacy in forecasting the proportion of fish initiating early male maturation in the spring (approximately 1 year prior to spermiation), compared to the proportion that actually matured. Combining measures of GSI, plasma 11KT, and pituitary fshb and lhb mRNA expression provided a useful, but conservative, estimate of the proportion of males initiating maturation in the spring (21%) compared to the proportion that were ultimately destined to mature (37%) the following spring. These results suggest that maturation may be less synchronous than previously appreciated and some males may have initiated maturation after our census in May.


Assuntos
Biomarcadores/metabolismo , Sistema Endócrino/metabolismo , Oncorhynchus mykiss/genética , Estações do Ano , Maturidade Sexual/genética , Transcriptoma/genética , Animais , Tamanho Corporal , Regulação da Expressão Gênica , Modelos Lineares , Masculino , Oncorhynchus mykiss/anatomia & histologia , Oncorhynchus mykiss/sangue , Hipófise/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Testículo/citologia , Testículo/metabolismo , Testosterona/análogos & derivados , Testosterona/sangue
18.
Gen Comp Endocrinol ; 280: 123-133, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31009604

RESUMO

Receptors for follicle-stimulating hormone (Fshr), luteinizing hormone (Lhcgr1 and Lhcgr2) and androgens (Ara and Arb) transduce the hormonal signals that coordinate spermatogenesis, but the factors that regulate the abundance of these transducers in fish testes remain little-understood. To mend this paucity of information, we first determined changes in transcript abundance for these receptors (fshr, lhcgr1, ara and arb) during spermatogenesis induced by human chorionic gonadotropin (hCG) injection in the eel, Anguilla australis. We related our findings to testicular production of the fish androgen, 11-ketotestosterone (11-KT), and to the levels of the transcripts encoding steroidogenic acute regulatory protein (star) and 11ß-hydroxylase (cyp11b), and subsequently evaluated the effects of hCG or 11-KT on mRNA levels of these target genes in vitro. Testicular 11-KT production was greatly increased by hCG treatment, both in vivo and in vitro, and associated with up-regulation of star and cyp11b transcripts. In situ hybridization indicated that testicular fshr mRNA levels were higher in the early stages of hCG-induced spermatogenesis, while lhcgr1 transcripts were most abundant later, once spermatids were observed. In vitro experiments further showed that hCG and its steroidal mediator 11-KT significantly increased fshr transcript abundance. These data provide new angles on the interactions between gonadotropin and androgen signaling during early spermatogenesis. Increases in levels of 11-KT following hCG injection elevated testicular fshr mRNA levels augmenting Fsh sensitivity in the testis. This evidence is suggestive of a positive feedback loop between gonadotropins and 11-KT that may be key to regulating early spermatogenesis in fish.


Assuntos
Anguilla/genética , Regulação da Expressão Gênica , Receptores Androgênicos/genética , Receptores da Gonadotropina/genética , Testículo/metabolismo , Androgênios/metabolismo , Anguilla/sangue , Animais , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Androgênicos/metabolismo , Receptores do FSH/genética , Receptores do FSH/metabolismo , Receptores da Gonadotropina/metabolismo , Receptores do LH/genética , Receptores do LH/metabolismo , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Esteroide 11-beta-Hidroxilase/genética , Esteroide 11-beta-Hidroxilase/metabolismo , Testículo/efeitos dos fármacos , Testosterona/análogos & derivados , Testosterona/sangue
19.
J Steroid Biochem Mol Biol ; 190: 242-249, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30959151

RESUMO

The androgen precursors, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are produced in high amounts by the adrenal cortex primarily in humans and a few other primates. The human adrenal also secretes 11-oxygenated androgens (11-oxyandrogens), including 11ß-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), 11ß-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT), of which 11OHT and 11KT are bioactive androgens. The 11-oxyandrogens, particularly 11KT, have been recognized as biologically important testicular androgens in teleost fishes for decades, but their physiological contribution in humans has only recently been established. Beyond fish and humans, however, the presence of 11-oxyandrogens in other species has not been investigated. This study provides a comprehensive analysis of a set of C19 steroids, including the traditional androgens and 11-oxyandrogens, across 18 animal species. As previously shown, serum DHEA and DHEAS were much higher in primates than all other species. Circulating 11-oxyandrogens, especially 11KT, were observed in notable amounts in male, but not in female trout, consistent with gonadal origin in fish. The circulating concentrations of 11-oxyandrogens ranged from 0.1 to 10 nM in pigs, guinea pigs and in all the primates studied (rhesus macaque, baboon, chimpanzee and human) but not in rats or mice, and 11OHA4 was consistently the most abundant. In contrast to fish, serum 11KT concentrations were similar in male and female primates for each species, despite significantly higher circulating testosterone in males, suggesting that 11KT production in these species is not testis-dependent and primarily originates from adrenal-derived 11-oxyandrogen precursors.


Assuntos
Androgênios/sangue , Sulfato de Desidroepiandrosterona/sangue , Desidroepiandrosterona/sangue , Testosterona/análogos & derivados , Animais , Feminino , Masculino , Especificidade da Espécie , Testosterona/sangue
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