Cancer is a leading cause of mortality in the United States. Despite much research on specific carcinogens, the cause of many cancers remains unclear. The identification of novel causative agents offers the potential for cancer prevention. Diseases such as obesity and diabetes mellitus, characterized by hyperinsulinemia, are associated with increased risk of endometrial, colorectal, and breast carcinomas. There is increasing evidence that insulin is a growth factor for tumor formation. The mechanisms underlying insulin-mediated neoplasia may include enhanced DNA synthesis with resultant tumor cell growth, inhibition of apoptosis, and altered sex hormone milieu. The reduced insulin levels seen with physical activity, weight loss, and a high fiber diet may account for decreased cancer risk. The role of newer drugs that restore sensitivity to insulin, thereby reducing hyperinsulinemia, is an exciting potential area of cancer prevention. In this review, we discuss the potential role of insulin as a tumor growth factor.

The objectives of this study are to characterize two carrier proteins in the horse that significantly decrease in humans following anabolic androgenic steroid administration: sex hormone-binding globulin (SHBG) and thyroxine-binding globulin (TBG). For SHBG characterization, qPCR, RNA sequencing, and immunohistochemistry were performed on testes and equine livers. Free and total testosterone immunoassays were utilized to confirm the presence of a carrier protein in equine circulation. SHBG was detected in the testes using qPCR, RNA sequencing, and IHC, indicating the presence of the isoform androgen-binding protein (ABP). SHBG was not detected in any liver samples. Evidence of a carrier protein was shown by free testosterone being significantly lower than the total testosterone that was detected in stallions (p < 0.0001) and pregnant mares (p < 0.0001). TBG characterization was completed using an equine specific TBG ELISA. Equine serum was analyzed across seasons, reproductive statuses, sexes, and ages. TBG concentrations were also measured following anabolic steroid administration (Stanozolol) and increased endogenous androgen production via hCG administration in stallions and aromatase inhibition via Letrozole administration in pregnant mares. TBG did not significantly differ across season, reproductive status, sex, or age Alterations of androgen concentrations did not result in any significant changes to circulating TBG concentrations.

No description available.

A ocitocina (OT) é um neuropeptídio hipotalâmico, que dentre suas funções na fêmea destaca-se a contração uterina durante o parto e a ejeção do leite. No entanto, estudos vêm demonstrando importantes funções endócrinas e parácrinas no trato reprodutivo masculino. Evidenciando a possível ação conjunta entre OT e a Globulina ligadora de hormônios sexuais (SHBG). Entretanto, em cães não existem informações disponíveis quanto sua atuação. Assim, estudos direcionados aos receptores de ocitocina (OTR) e SHBG e suas funções no sistema reprodutor masculino, mais especificamente na fisiologia espermática, são de suma importância para os conhecimentos da fisiologia reprodutiva para posterior aplicação em biotecnologias reprodutivas em pequenos animais e humanos, fomentando também novas perspectivas para a utilização terapêutica da ocitocina em enfermidades reprodutivas. Portanto, o objetivo deste estudo é verificar a expressão gênica e proteica do OTR e SHBG no testículo e epidídimo de cães, correlacionando tais dados com a qualidade espermática e dosagem de testosterona. Para tal, foram coletados testículos e epidídimos de 26 cães em idade reprodutiva (1 a 5 anos). Após a orquiectomia, foi realizada a coleta dos espermatozoides provenientes da cauda do epidídimo e então, as amostras foram analisadas quanto à motilidade computadorizada do sêmen (CASA), integridade de membrana plasmática (Eosina/Nigrosina), integridade de membrana acrossomal (Fast Green / Rosa Bengala) e atividade mitocondrial (3´3 Diaminobenzidine). A imunolocalização do OTR e SHBG foi realizada através de imunoistoquímica e imunofluorescência. E a análise de expressão gênica, através da Reação em cadeia da polimerase em tempo real (qRT PCR). E da expressão proteica, através do Western Blotting. Foram encontradas correlações significantes e positivas entre as expressões gênicas do OTR e do SHBG, tanto no testículo como no epidídimo. Além disto, a expressão do OTR no testículo correlacionou-se positivamente com espermatozoides com membrana acrossomal íntegra e negativamente com a porcentagem de células com baixa atividade mitocondrial. Já o SHBG do testículo, correlacionou-se positivamente com a concentração de espermatozoides, porcentagens de células com membrana plasmática e acrossomal íntegras, motilidade, motilidade progressiva e velocidade rápida, e negativamente com a porcentagem de células com baixa atividade mitocondrial. Por outro lado, no epidídimo, a expressão gênica do SHBG apresentou correlação positiva com a porcentagem de células com membrana plasmática íntegra e expressão proteica de SHBG no testículo. Quanto a expressão proteica, o OTR no testículo obteve correlação positiva com testosterona e negativa com atividade mitocondrial nula, já no epidídimo, ocorreu correlação positiva com integridade de membrana acrossomal e negativa também com atividade mitocondrial nula. Em relação ao SHBG, houve correlação positiva com a expressão gênica do SHBG no epidídimo, células normais e padrões de velocidade. E na imunoistoquímica foi possível observar a imunomarcação do OTR e SHBG na musculatura lisa e células de Leydig do testículo e OTR na musculatura lisa do epidídimo. No entanto, não houve imunomarcação do SHBG no epidídimo, assim como expressão proteica. Nossos resultados demonstraram que o OTR e SHBG são expressos nos testículos e epidídimos de cães e que estão relacionados a funções espermáticas importantes, sendo essenciais para o sucesso reprodutivo / Oxytocin (OT) is a hypothalamic neuropeptide that plays important and well known roles in the female such as uterine contraction during childbirth and milk ejection. Notwithstanding, studies have shown important endocrine and paracrine functions also in the male reproductive tract, highlighted by the possible joint action between OT and sex hormone-binding globulin (SHBG). In dogs, however, there is no information available with regards to the role of these hormones in the reproductive function. Thus, studies directed to oxytocin (OTR) and SHBG receptors and their functions in the male reproductive system, specifically with regards to sperm physiology. Such knowledge is essential to understand the reproductive physiology for the subsequent use in reproductive biotechnologies in small animals and humans, especially by providing new perspectives for the therapeutic use of oxytocin in reproductive disorders. Therefore, the aim of this study is to assess the gene and protein expression of OTR and SHBG in the testis and epididymis of dogs, correlating these data with sperm quality and testosterone dosage. To this end, testis and epididymis were collected from 26 dogs in reproductive age (1 to 5 years). After orchiectomy, collection of sperm from the cauda epididymis was carried out and then the samples were analyzed for computerized motility of semen (CASA), plasma membrane integrity (eosin / nigrosine), acrosome membrane integrity (Fast Green / rose Bengal) and mitochondrial activity (3\'3 Diaminobenzidine). The immunolocalization of OTR and SHBG was performed by immunohistochemistry and immunofluorescence. Gene expression analysis was performed by real time polymerase chain reaction (qRT - PCR). The protein expression was further assessed by Western Blotting. Significant positive correlations were found between the gene expressions of OTR and SHBG in both the testis and epididymis. Furthermore, the OTR expression in testis was positively correlated to sperm with intact acrosome membrane and negatively to the percentage of cells with low mitochondrial activity. On the other hand, testicular SHBG was positively correlated with sperm concentration, percentage of sperm with intact plasma membrane and acrosome, motility, progressive motility and the percentage of RAPID sperm. Also, negative correlation was found between testicular SHBG and the percentage of cells with low mitochondrial activity. Furthermore, in the epididymis, SHBG gene expression was positively correlated to the percentage of cells with intact plasma membrane and protein expression of SHBG in the testis. In relation to the protein expression, the OTR in the testis correlated positively with blood plasma testosterone and negatively with sperm with no mitochondrial activity. In the epididymis, OTR protein expression correlated positively with sperm showing intact acrosome and negatively with cells with no mitochondrial activity. With regards to SHBG proteins expression, there was a positive correlation to SHBG gene expression in the epididymis, normal cells and some patterns of sperm velocity. In the immunohistochemistry, we observed the OTR and SHBG immunostainings in the smooth muscle and Leydig cells of the testis while, in the epididymis, the OTR immunostaining could be observed only in the smooth muscle. Interestingly, there was no immunostaining or protein expression of SHBG in the epididymis. Our results demonstrated that OTR and SHBG are expressed in the testis and epididymis of dogs and are related to important sperm functions, essential for reproductive success

Objective To determine the relationship between increased body hair growth in women and serum sex hormone level, body mass index, and clinical signs. Sample and methods The sample group consisted of 186 women, 18–35 year old residents of Lithuania who were referred to the Clinic of Endocrinology, Kaunas University of Medicine Hospital in 2002–2004 and complained for increased body hair growth. Exclusion criteria: 1) taking systemic medications within the period shorter than three months before the beginning of the study; 2) specific reasons of excessive body hair growth, such as androgen secreting adrenal or ovarian tumors, hyperprolactinemia, Cushing syndrome; 3) thyroid dysfunction. A total number of 37 women were excluded from further study. Statistical analysis was performed on 149 women. Increased body hair growth was assessed using Ferriman-Gallwey (F-G) method. Blood samples were drawn in the morning (08:00–10:00 h), in the early follicular phase, with an exclusion of 7 women with amenorrhea, while the blood sample of 12 women with oligomenorrhea was drawn following at least 2 months after the last menstruation. Serum hormones (total testosterone (T), sex hormone binding globulin (SHBG), free androgen index (FAI), dehydroepiandrosterone sulphate (DHEAS) level were measured using the commercial kits. FAI was calculated as follows: T (nmol/l) × 100/ SHBG (nmol/l). Results The significance of correlations between the F-G score and the tested variables decreased in the... [to full text]

A ocitocina (OT) é um neuropeptídio hipotalâmico, que dentre suas funções na fêmea destaca-se a contração uterina durante o parto e a ejeção do leite. No entanto, estudos vêm demonstrando importantes funções endócrinas e parácrinas no trato reprodutivo masculino. Evidenciando a possível ação conjunta entre OT e a Globulina ligadora de hormônios sexuais (SHBG). Entretanto, em cães não existem informações disponíveis quanto sua atuação. Assim, estudos direcionados aos receptores de ocitocina (OTR) e SHBG e suas funções no sistema reprodutor masculino, mais especificamente na fisiologia espermática, são de suma importância para os conhecimentos da fisiologia reprodutiva para posterior aplicação em biotecnologias reprodutivas em pequenos animais e humanos, fomentando também novas perspectivas para a utilização terapêutica da ocitocina em enfermidades reprodutivas. Portanto, o objetivo deste estudo é verificar a expressão gênica e proteica do OTR e SHBG no testículo e epidídimo de cães, correlacionando tais dados com a qualidade espermática e dosagem de testosterona. Para tal, foram coletados testículos e epidídimos de 26 cães em idade reprodutiva (1 a 5 anos). Após a orquiectomia, foi realizada a coleta dos espermatozoides provenientes da cauda do epidídimo e então, as amostras foram analisadas quanto à motilidade computadorizada do sêmen (CASA), integridade de membrana plasmática (Eosina/Nigrosina), integridade de membrana acrossomal (Fast Green / Rosa Bengala) e atividade mitocondrial (3´3 Diaminobenzidine). A imunolocalização do OTR e SHBG foi realizada através de imunoistoquímica e imunofluorescência. E a análise de expressão gênica, através da Reação em cadeia da polimerase em tempo real (qRT PCR). E da expressão proteica, através do Western Blotting. Foram encontradas correlações significantes e positivas entre as expressões gênicas do OTR e do SHBG, tanto no testículo como no epidídimo. Além disto, a expressão do OTR no testículo correlacionou-se positivamente com espermatozoides com membrana acrossomal íntegra e negativamente com a porcentagem de células com baixa atividade mitocondrial. Já o SHBG do testículo, correlacionou-se positivamente com a concentração de espermatozoides, porcentagens de células com membrana plasmática e acrossomal íntegras, motilidade, motilidade progressiva e velocidade rápida, e negativamente com a porcentagem de células com baixa atividade mitocondrial. Por outro lado, no epidídimo, a expressão gênica do SHBG apresentou correlação positiva com a porcentagem de células com membrana plasmática íntegra e expressão proteica de SHBG no testículo. Quanto a expressão proteica, o OTR no testículo obteve correlação positiva com testosterona e negativa com atividade mitocondrial nula, já no epidídimo, ocorreu correlação positiva com integridade de membrana acrossomal e negativa também com atividade mitocondrial nula. Em relação ao SHBG, houve correlação positiva com a expressão gênica do SHBG no epidídimo, células normais e padrões de velocidade. E na imunoistoquímica foi possível observar a imunomarcação do OTR e SHBG na musculatura lisa e células de Leydig do testículo e OTR na musculatura lisa do epidídimo. No entanto, não houve imunomarcação do SHBG no epidídimo, assim como expressão proteica. Nossos resultados demonstraram que o OTR e SHBG são expressos nos testículos e epidídimos de cães e que estão relacionados a funções espermáticas importantes, sendo essenciais para o sucesso reprodutivo / Oxytocin (OT) is a hypothalamic neuropeptide that plays important and well known roles in the female such as uterine contraction during childbirth and milk ejection. Notwithstanding, studies have shown important endocrine and paracrine functions also in the male reproductive tract, highlighted by the possible joint action between OT and sex hormone-binding globulin (SHBG). In dogs, however, there is no information available with regards to the role of these hormones in the reproductive function. Thus, studies directed to oxytocin (OTR) and SHBG receptors and their functions in the male reproductive system, specifically with regards to sperm physiology. Such knowledge is essential to understand the reproductive physiology for the subsequent use in reproductive biotechnologies in small animals and humans, especially by providing new perspectives for the therapeutic use of oxytocin in reproductive disorders. Therefore, the aim of this study is to assess the gene and protein expression of OTR and SHBG in the testis and epididymis of dogs, correlating these data with sperm quality and testosterone dosage. To this end, testis and epididymis were collected from 26 dogs in reproductive age (1 to 5 years). After orchiectomy, collection of sperm from the cauda epididymis was carried out and then the samples were analyzed for computerized motility of semen (CASA), plasma membrane integrity (eosin / nigrosine), acrosome membrane integrity (Fast Green / rose Bengal) and mitochondrial activity (3\'3 Diaminobenzidine). The immunolocalization of OTR and SHBG was performed by immunohistochemistry and immunofluorescence. Gene expression analysis was performed by real time polymerase chain reaction (qRT - PCR). The protein expression was further assessed by Western Blotting. Significant positive correlations were found between the gene expressions of OTR and SHBG in both the testis and epididymis. Furthermore, the OTR expression in testis was positively correlated to sperm with intact acrosome membrane and negatively to the percentage of cells with low mitochondrial activity. On the other hand, testicular SHBG was positively correlated with sperm concentration, percentage of sperm with intact plasma membrane and acrosome, motility, progressive motility and the percentage of RAPID sperm. Also, negative correlation was found between testicular SHBG and the percentage of cells with low mitochondrial activity. Furthermore, in the epididymis, SHBG gene expression was positively correlated to the percentage of cells with intact plasma membrane and protein expression of SHBG in the testis. In relation to the protein expression, the OTR in the testis correlated positively with blood plasma testosterone and negatively with sperm with no mitochondrial activity. In the epididymis, OTR protein expression correlated positively with sperm showing intact acrosome and negatively with cells with no mitochondrial activity. With regards to SHBG proteins expression, there was a positive correlation to SHBG gene expression in the epididymis, normal cells and some patterns of sperm velocity. In the immunohistochemistry, we observed the OTR and SHBG immunostainings in the smooth muscle and Leydig cells of the testis while, in the epididymis, the OTR immunostaining could be observed only in the smooth muscle. Interestingly, there was no immunostaining or protein expression of SHBG in the epididymis. Our results demonstrated that OTR and SHBG are expressed in the testis and epididymis of dogs and are related to important sperm functions, essential for reproductive success

Our lab has previously reported the identification of a novel endogenous 19-nor steroid, estradienolone (ED), in pregnant women that strongly bound to sex hormone binding globulin. Estrogen-receptor related receptors (ERRs), which have no known natural ligands, are a family of orphan receptors consisting of 3 isoforms: ERRalpha, ERRbeta and ERRgamma. The ERRs have been shown to actively modulate estrogenic responses, to play an essential role in pregnancy, and are implicated in breast cancer prognosis. My results show that ED acts as an antagonist of the ERRalpha confirming preliminary results obtained by our group. Studies of cellular responses demonstrate that ED has strong anti-mitogenic properties. ED inhibited the growth of both estrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) breast cancer cells in a dose-dependent manner but did not have any effects on the proliferation of the non-cancerous immortalized epithelial breast MCF-10A cells. The finding that ED inhibits proliferation of both ER negative and ER positive breast cancer cells, and regulate ERR transcriptional activity may have important ramifications in breast cancer therapy.

Made available in DSpace on 2015-07-22T20:50:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-04-28 / Introdução: As doenças cardiovasculares (DCVs) representam o principal grupo de causa de morte no Brasil, com destaque para doença arterial coronariana (DAC). O sexo masculino apresenta maior incidência e mortalidade por DAC que o feminino. Uma das explicações para o fato era o possível efeito deletério da Testosterona no sistema cardiovascular masculino e o efeito protetor do Estradiol no sistema cardiovascular feminino. Contudo, evidências recentes da literatura apontam para um efeito protetor ou neutro da Testosterona no aparelho cardiovascular masculino, enquanto níveis elevados de Estradiol nos homens estiveram correlacionados com maior morbidade e mortalidade por doenças cardiovasculares. Objetivos: Realizar uma revisão da literatura da relação existente entre Testosterona sérica e doença cardiovascular em homens adultos; Avaliar a relação existente entre Testosterona Total, Testosterona Biodisponível, Testosterona Livre, Índice de Andrógenos Livres (IAL), Globulina Ligadora de Esteróides Sexuais (SHBG), Estradiol, Índice de Estrógenos Livres (IEL), relação Estradiol / Testosterona e a relação IEL / IAL e doença arterial coronariana em homens adultos; Entender o papel da Globulina Ligadora de Esteróides Sexuais como novo componente as síndrome metabólica. Material e Métodos: A revisão da relação entre testosterona e doença cardiovascular foi realizada através da base de dados do PubMed com a utilização dos unitermos testosterona e doença cardiovascular; a avaliação da relação existente entre esteróides sexuais e DAC foi realizada através de um estudo de caso controle com homens adultos submetidos ao Cateterismo de Artérias Coronárias no Instituto Dante Pazzanese de Cardiologia; o entendimento do papel da SHBG como novo componente as síndrome metabólica através da análise dos dados obtidos do estudo “Estradiol but not Testosterone is Related to Coronary Artery Disease”. Resultados: Os resultados foram dispostos em 03 artigos, a saber: ARTIGO 1 “Testosterona Sérica e Doença Cardiovascular em Homens”; ARTIGO 2 “Estradiol but not Testosterone is Related to Coronary Artery Disease in Men”; ARTIGO 3 (preparando para a submissão) “Sex hormone binding globulin a novel component of metabolic syndrome”. Conclusões: Os estudos selecionados da literatura que avaliaram a relação entre testosterona e doença cardiovascular apresentavam pequeno número de participantes e amostras selecionadas, ornando necessário que novos estudos avaliem o papel da testosterona na DCV nos homens. Os achados apresentados sinalizam para uma correlação positiva entre níveis séricos de Estradiol e IEL com DAC. Foram observados efeitos neutros da testosterona total, testosterona biodisponível, testosterona livre, índice de andrógenos livres SHBG, relação Estradiol / Testosterona e relação IEL / IAL na incidência dessa patologia. Baixos níveis de SHBG parecem se correlacionar positivamente com os componentes da síndrome metabólica, sendo necessários novos estudos que avaliem esse parâmetro como novo componente desta Síndrome. / Introduction: Cardiovascular diseases (CVDs) represent the main cause of death in Brazil, and among them especially the coronary artery diseases (CADs). Men present higher incidence and mortality rates for CAD than women. One of the explanations for this fact may be the possibly deleterious effect of testosterone on the male cardiovascular system and the protective effect of estradiol on the female cardiovascular system. However, recent studies in the literature indicate that testosterone has an either protective or neutral effect on the male cardiovascular system, while high levels of estradiol in men have been correlated to higher rates of morbidity and mortality from cardiovascular diseases. Objectives: To carry out a review of the literature regarding the relationship between testosterone and cardiovascular disease in men, to evaluate the existing relationships among total testosterone, bioavailable testosterone, free testosterone, free androgen index (FAI), sex hormone binding globulin, estradiol, free estrogen index (FEI), estradiol/testosterone ratio and FEI/FAI ratio and coronary artery disease in men; to understand the role of the sex hormone binding globulin as a new component of the metabolic syndrome. Material and Methods: The review of the literature regarding the relationship between testosterone and cardiovascular disease was performed using the PubMed database and the keywords testosterone and cardiovascular disease. The relationship between sex steroids and CAD was evaluated by a case-control study performed on men submitted to coronary angiography at the Instituto Dante Pazzanese de Cardiologia. The role of the sex hormone binding globulin (SHBG) as a new component of the metabolic syndrome was evaluated using the data obtained by the study “Estradiol but not Testosterone is Related to Coronary Artery Disease”. Results: The results were presented in three articles, namely: ARTICLE 1 - “Serum Testosterone and Cardiovascular Disease in Men”; ARTICLE 2 - “Estradiol but not Testosterone is Related to Coronary Artery Disease in Men”; ARTICLE 3 - (being prepared for submission) - “Sex hormone binding globulin, the novel component of metabolic syndrome?”. Conclusions: The studies retrieved from the literature which evaluated the relationship between testosterone and cardiovascular disease presented small numbers of participants and selected samples, which indicated the need for further studies to evaluate the role of testosterone in CVD in men. The findings presented suggest a positive correlation between estradiol and FEI levels with CAD. A neutral effect of total testosterone, bioavailable testosterone, free testosterone, free androgen index, SHBG, estradiol/testosterone ratio and FEI/FAI ratio on the incidence of this pathology was observed. Low levels of SHBG seem to correlate positively with the components of the metabolic syndrome, but further studies are necessary to evaluate this parameter as a new component of this syndrome. / TEDE / BV UNIFESP: Teses e dissertações

No description available.

Background: Exposure to perfluorooctane sulfonic acid (PFOS) or to perfluorooctanoic acid (PFOA) increases mouse and human peroxisome proliferator–activated receptor alpha (PPARα) subtype activity, which influences lipid metabolism. Because cholesterol is the substrate from which testosterone is synthesized, exposure to these substances has the potential to alter testosterone concentrations. Objectives: We explored associations of total testosterone and sex hormone–binding globulin (SHBG) concentrations at age 15 years with prenatal exposures to PFOS, PFOA, perfluorohexane sulfonic acid (PFHxS), and perfluoronanoic acid (PFNA) in females. Methods: Prenatal concentrations of the perfluoroalkyl acids (PFAAs) were measured in serum collected from pregnant mothers at enrollment (1991–1992) in the Avon Longitudinal Study of Parents and Children (ALSPAC). The median gestational age when the maternal blood sample was obtained was 16 weeks (interquartile range, 11–28 weeks). Total testosterone and SHBG concentrations were measured in serum obtained from their daughters at 15 years of age. Associations between prenatal PFAAs concentrations and reproductive outcomes were estimated using linear regression models (n = 72). Results: Adjusted total testosterone concentrations were on average 0.18-nmol/L (95% CI: 0.01, 0.35) higher in daughters with prenatal PFOS in the upper concentration tertile compared with daughters with prenatal PFOS in the lower tertile. Adjusted total testosterone concentrations were also higher in daughters with prenatal concentrations of PFOA (β = 0.24; 95% CI: 0.05, 0.43) and PFHxS (β = 0.18; 95% CI: 0.00, 0.35) in the upper tertile compared with daughters with concentrations in the lower tertile. We did not find evidence of associations between PFNA and total testosterone or between any of the PFAAs and SHBG. Conclusions: Our findings were based on a small study sample and should be interpreted with caution. However, they suggest that prenatal exposure to some PFAAs may alter testosterone concentrations in females.