No / Red deer stags produce an androgen-dependent mane of long hairs only in the breeding season; in the non-breeding season, when circulating androgen levels are low, the neck hair resembles the rest of the coat. This study was designed to determine whether androgen receptors are present in deer follicles throughout the year or only in the mane (neck) follicles when circulating testosterone levels are high in the breeding season. Although androgens regulate much human hair growth the mechanisms are not well understood; they are believed to act on the hair follicle epithelium via the mesenchyme-derived dermal papilla. The location of androgen receptors in the follicle was investigated by immunohistochemistry and androgen binding was measured biochemically in cultured dermal papilla cells derived from mane and flank follicles during the breeding season and from neck follicles during the non-breeding season. Immunohistochemistry of frozen skin sections using a polyclonal antibody to the androgen receptor localised nuclear staining only in the dermal papilla cells of mane follicles. Saturation analysis assays of 14 primary dermal papilla cell lines using [(3)H]-mibolerone demonstrated high-affinity, low-capacity androgen receptors were present only in mane (breeding season neck) cells; competition studies with other steroids confirmed the specificity of the receptors. Androgen receptors were not detectable in cells from either the breeding season flank nor the non-breeding season neck follicles. The unusual biological model offered by red deer of androgen-dependent hair being produced on the neck in the breeding, but not the non-breeding season, has allowed confirmation that androgen receptors are required in follicle dermal papilla cells for an androgen response; this concurs with previous human studies. In addition, the absence of receptors in the non-breeding season follicles demonstrates that receptors are not expressed unless the follicle is responding to androgens. Androgen receptors may be induced in mane follicles by seasonal changes in circulating hormone(s).

Endometrial cancer is the most common gynecologic cancer with 54,870 cases occurring in the United States in 2015 and causing 10,170 deaths, an 18.5% mortality rate (Elit and Reade, 2015). Ovarian cancer, while less common, is much more fatal. In 2015 in the United States, 21,290 cases occurred and resulted in 14,180 deaths, a 66.6% mortality rate. This mortality rate makes ovarian cancer the fifth most deadly cancer for women in the United States, which is largely explained by ineffective screening strategies and limited treatment possibilities (Cramer, 2012). Thus, developing effective prevention strategies is especially important to saving the lives of women who will develop ovarian or endometrial cancer. Women taking combined oral contraceptives (COCs), a type of hormonal birth control, have shown a significant reduced risk of developing ovarian and endometrial cancer. However, the Centers for Disease Control and Prevention (CDC) does not currently recommend taking COCs for the prevention gynecologic cancer (CDC, 2014a). Since the efficacy of COCs for reducing risk of ovarian and endometrial cancer is well established, guidelines need to be determined for populations of women that should take hormonal birth control to minimize cancer risk. This paper highlights the current understanding of ovarian and endometrial cancer, populations of women at highest risk for developing either of these two cancers, and then proposes a case-control study to help determine which populations of women should take hormonal birth control to reduce their gynecologic cancer risk.

Background: Cancer is the second leading cause of death in economically developed countries. The use and availability of oral treatment for cancer has increased dramatically in the past 10 years. Few studies have described the use of oral chemotherapy in non-traditional ambulatory settings by health care professionals across different specialties. Objective: The purpose of this study is to describe the usage of oral chemotherapeutic medications in ambulatory settings. Methods: Cross sectional study of 2007 NAMCS Survey analysis involving 21,761 subjects aged 18 years and above with cancer who participated in the 2007 National Ambulatory Medical Survey (NAMCS). Main Outcome Measure: Physician-reported use of oral chemotherapeutic medications (includes all major drug classes) as indicated on questionnaire for 2007 NAMCS survey. Results: Health care providers in non-traditional settings are less likely to prescribe oral chemotherapy than in traditional ambulatory settings (Adjusted odds ratio (AOR)=0.65{95% confidence interval: 0.61-0.69}). The study results suggest that oncologists are prescribing oral anti-cancer drugs the most as compared to other physician specialties. Conclusion: Health care providers in non-traditional settings are less likely to prescribe oral chemotherapy than in traditional ambulatory settings. Primary care physicians may have limited experience in monitoring and prescribing these potentially toxic medications. Clear guidelines are required for the use of oral chemotherapy medications, considering the potential for their use in non-traditional ambulatory settings and by non-oncologists.

The importance of sex hormones in formation, development and regulation of sexually dimorphic behavior does not need to be stressed. However, their actual organizational and activational effects and interactions in sexual differentiation and determination are not fully understood yet. The aim of our study was to explore the effects of hormonal manipulation in eyelid-geckos (family Eublepharidae) and enlighten the role of steroid hormones in formation of sexual differences. In the first part of our work we tried to reverse sex of Yucatán banded gecko (Coleonyx elegans) by hormonal manipulation in the early embryogenesis. This species has genotypic sex determination with chromosome set X1X2Y. In reverted individuals we aimed to examine the effects of steroid hormones on sexually dimorphic traits and in case of full sexual reversion and fertility of progeny, we would search for the sex-determining gene. In the second part, we studied masculinization effects of testosterone in females of leopard gecko (Eublepharis macularius). In contrast with the Coleonyx elegans mentioned above, this species has temperature dependent sex determination, even though these two species are closely related. Experimental females were implanted with testosterone implants and therefore their testosterone levels were increased in...

Le cancer du sein est un problème majeur de santé publique en Amérique Latine (AL). Il a été montré que le surpoids, l'obésité, et les traitements hormonaux sont des facteurs de risque majeurs pour le développement du cancer du sein. Toutefois ces associations restent incertaines dans les populations d'AL. Le but de cette Thèse est donc de contribuer à combler ces lacunes en développant des études sur l'impact du surpoids et de l'obésité, ainsi que des traitements hormonaux, dans des populations latino-américaines. Nous avons donc utilisé les données originales d'une étude cas-témoins basée sur la population Mexicaine. Préalablement à cette étude, nous avons conduit une méta-analyse sur l'obésité et le cancer du sein chez la femme pré-ménopausée à travers le monde. Cette méta-analyse montre qu'à l'exception des Asiatiques, les personnes qui ont un indice de masse corporelle (IMC) élevé ont un risque diminué de cancer du sein pré-ménopausique tandis que celles qui ont un rapport tour de taille/hanches (RTH) élevé ont un risque du cancer du sein accru. L'étude cas-témoins montre une association inverse entre l'IMC élevé et le risque de cancer du sein en pré-ménopause tandis qu'en post ménopause aucune association n'a été observée. Cependant, le tour de taille, de hanche, et le RTH s'avèrent également inversement associés au risque de cancer du sein en pré et post-ménopause. D'autre part, l'augmentation de la silhouette tout au long de la vie est associée à un risque accru de cancer du sein. L'utilisation des traitements hormonaux substitutifs à la ménopause est également associée à un risque accru de cancer du sein. Cette étude apporte de nouvelles informations sur l'impact de ces facteurs sur le risque de cancer du sein / Breast cancer is a major public health problem in Latin America (LA). It has been shown that, overweight, obesity, and hormonal treatments are major risk factors for breast cancer development. However, these associations remain uncertain among Latin American populations. The aim of this thesis is to contribute to fill these gaps by developing studies on the impact of overweight and obesity, and hormonal treatments in Latin American populations. We used the original data from a multi-center population-based case–control study conducted in Mexico. Prior to this study, we conducted a dose-response meta-analysis on obesity and premenopausal breast cancer. This meta-analysis shows that, in the exception of Asians, increase in body mass index was inversely associated with the risk of premenopausal breast cancer; whereas, increase in waist-to-hip ratio are associated with an increase of this risk. The results of the case-control study show an inverse association between high BMI and the risk of breast cancer in pre-menopausal women, whereas no association was observed among post-menopausal. However, other anthropometric measures (waist and hip circumference, and waist hip ratio) are also inversely associated with risk of breast cancer in pre and post-menopausal women. Further analysis of body shape evolution throughout life showed significant increase in risk of breast cancer among women with increasing silhouettes size over time. With regards to menopausal hormone replacement therapy, users have a significant increased risk of breast cancer. This study provides new information about the effects of these factors on breast cancer risk, which may be of relevance for the population of LA as a whole

Depuis sa première description par James Parkinson dans son essai sur la paralysie agitante, la maladie de Parkinson (PD) a été reconnue comme une maladie du système moteur identifié par une tétrade de symptômes, à savoir : akinésie, rigidité musculaire, tremblement au repos et instabilité posturale. Ces symptômes sont liés à la perte de la dopamine (DA) dans le striatum après la dégénérescence neuronale dans la substance noire (SN). Il est de plus en plus reconnu que les symptômes non moteurs et peut-être non dopaminergiques inévitablement émergent et s'aggravent au cours de la progression de la maladie. Les perturbations du sommeil sont parmi les principaux symptômes non moteurs et ont été reconnus comme marqueurs précliniques de la maladie. Les modèles de régulation du sommeil ont insisté sur deux processus distincts : un mécanisme de contrôle du sommeil, ou homéostat sommeil, et un oscillateur circadien. L'oscillateur circadien, basé dans le noyau suprachiasmatique (NSC) est responsable de la tendance à dormir pendant certaines phases du cycle de 24 heures et la consolidation du sommeil et de réveil en épisodes distincts. L'homéostat sommeil est chargé de surveiller et de réagir à la nécessité pour le sommeil, provoquant l'envie de dormir à dépendre sur les montants avant du sommeil ou de l'éveil. Alors que les perturbations dans les circuits et les processus homéostatiques impliqués dans la régulation du sommeil-éveil comportement sont documenté dans la maladie de Parkinson, l'implication potentielle des altérations du système circadien n'ont pas été étudiés en détail. Le but de ma thèse est d'étudier les modifications dans le système circadien en utilisant deux modèles animaux de PD : la souris et le primate non-humain / Since the first description by James Parkinson in his essay on the shaking palsy, Parkinson’s disease (PD) was recognized as a motor disease identified by a tetrad of symptoms, namely; akinesia, muscular rigidity, resting tremor and postural instability. These symptoms are known to be related to loss of dopamine (DA) in the striatum following neural degeneration in the substantia nigra (SN). It is increasingly recognized that non-motor and perhaps non-dopaminergic related symptoms inevitably emerge and worsen during disease progression. Sleep disruption is one of the major non-motor symptoms and has been suggested as a preclinical marker of the disease. Models of sleep regulation have emphasized two distinct processes: a sleep-control mechanism, or sleep homeostat, and a circadian oscillator. The circadian oscillator, based in the suprachiasmatic nucleus (SCN), is responsible for the tendency to sleep during certain phases of the 24-hour cycle and the consolidation of sleep and wake into distinct episodes. The sleep homeostat is responsible for monitoring and reacting to the need for sleep, causing the urge to sleep to depend on prior amounts of sleep or wakefulness. While disruptions in the circuitry and the homeostatic processes involved in the regulation of sleep-wake behaviour is will documented in PD, the potential involvement of alterations of the circadian system have not been studied in detail. The aim of my thesis is to investigate alterations in the circadian timing system using two animal models of PD: the mouse and the non-human primate. Taken together, the studies show that disturbances of circadian functions occur after MPTP treatment in the non-human primate but not in the mouse model of PD. These results emphasize the limitations of the MPTP-treated mouse model of PD for the study of non-motor symptoms, and reinforce previous studies that question the adequacy of this model to replicate cardinal motor features of the disease. In contrast, results in the non-human primate model stress the importance of dopaminergic degeneration in the circadian organisation of behavioral sleep wake cycle in PD

A pós-menopausa é marcada por alterações fisiológicas hemodinâmicas e metabólicas. A terapia de reposição estrogênica é uma forma de amenizar as conseqüências da deficiência hormonal e o exercício físico contribui significativamente para a redução do risco cardiovascular. O objetivo desse estudo foi avaliar em mulheres pós-menopausadas os efeitos isolados e associados da terapia oral estrogênica (TRH) e do treinamento físico aeróbio (TF) nas respostas hemodinâmicas e neurais basais e durante os exercícios com handgrip. Quarenta e cinco mulheres (51±3 anos), histerectomizadas, com e sem ovários, saudáveis, realizaram uma sessão experimental e, posteriormente foram divididas em 4 grupos SED-PLA (n=11), SED-TRH (n=14), TF-PLA (n=12) e TF-TRH (n=8). Os grupos TRH e receberam valerato de estradiol 1mg/dia; PLA receberam placebo; TF, realizaram exercício aeróbio em cicloergômetro por 50 minutos, 3 vezes por semana e SED permaneceram sedentárias. Todas as voluntárias participaram de uma segunda sessão experimental após 6 meses de acompanhamento. Nas sessões experimentais foram avaliadas a atividade nervosa simpática periférica (ANSP - microneurografia), pressão arterial, freqüência cardíaca (FC - método oscilométrico Dixtal no membro inferior), fluxo sangüíneo do antebraço (FSA - pletismografia) em um período basal e durante exercícios estático e dinâmico com handgrip a 30% da força de contração máxima. Para análise estatística foi utilizada ANOVA. O TF isoladamente diminuiu ANSP de 40±7 a 34±4 impulsos/min, (P=0,01) e aumentou FSA de 1,92±0,96 a 2,65±1,34 ml(min.100ml), P=0,03 no período basal. TRH e TF associados reduziram a FC no período basal de 65±8 para 62±7 bpm (P=0,01) e durante o exercício estático e dinâmico com handgrip. A TRH de maneira isolada ou associada ao TF diminuiu as respostas de FC durante os exercícios estático e dinâmico com handgrip. Em conclusão, as intervenções de maneira isolada ou associada promovem alterações hemodinâmicas e neurais que podem contribuir para redução do risco cardiovascular de mulheres pós-menopausadas saudáveis. / The post-menopause is marked by physiological hemodynamic and metabolic changes. The estrogen replacement therapy is a way to reduce the consequences of hormone deficiency and physical exercise contributes significantly to the reduction of cardiovascular risk. The aim of this study was to evaluate in post-menopausal women the isolated and associated effects of oral estrogen therapy (TRH) and physical training (TF) in the neural and hemodynamic responses during baseline and \"handgrip\" exercises. Forty-five women (51 ± 3 years), hysterectomized, with or without ovaries, healthy, participated of an initial session and then they were divided into 4 groups SEDPLA (n = 11), SED-TRH (n = 14), TF-PLA (n = 12) and TF-TRH (n = 8). The TRH groups received estradiol valerate 1 mg / day; PLA placebo; TF, performed aerobic exercise on a cycle ergometer for 50 minutes, 3 times a week and SED remained sedentary. All subjects participated in a second experimental session after 6 months of follow-up. In the experimental sessions peripheral sympathetic nerve activity (ANSP - microneurography), blood pressure, heart rate (FC - oscillometry - Dixtal lower limb), forearm blood flow (FSA - plethysmography) were evaluated at the baseline period and during static and dynamic \"handgrip\" exercises at 30% of the maximum force. ANOVA was used for the statistica analysis. The TF alone decreased ANSP from 40 ± 7 to 34 ± 4 bursts/min, P = 0.01 and increased FSA 1.92 ± 0.96 to 2.65 ± 1.34 ml (min.100ml), P = 0.03 at the baseline. The association of TRH and TF reduced HR at the baseline from 65 ± 8 to 62 ± 7 bpm (P=0.01) and during exercise with static and dynamic \"handgrip\". HRT alone or associated with TF decreased the HR responses during static and dynamic \"handgrip exercises. In conclusion, the interventions alone or in an associated way promote neural and hemodynamic changes that may contribute to cardiovascular risk reduction in healthy postmenopausal women.

O exercício aeróbico é recomendado para indivíduos pré-hipertensos como prevenção da hipertensão arterial. Uma única sessão de exercício aeróbico promove hipotensão pósexercício. Estudos prévios com normotensos observaram menor hipotensão pós-exercício pela manhã do que ao final da tarde, porém, estes estudos não incluíram uma situação controle (sem exercício) e avaliaram apenas alguns determinantes hemodinâmicos desse fenômeno. Dessa forma, o objetivo deste estudo foi analisar e comparar a resposta da pressão arterial (PA) e seus determinantes hemodinâmicos e mecanismos autonômicos após uma sessão de exercício aeróbico realizado pela manhã (9:00 h) e ao final do dia (18:30 h), relacionando os resultados obtidos com os efeitos deste exercício em alguns marcadores neuro-hormonais do ritmo circadiano. Para tanto, 16 homens pré-hipertensos participaram de 4 sessões experimentais conduzidas em ordem aleatória: duas pela manhã e duas ao final do dia. Em cada fase do dia, foram realizadas uma sessão controle (repouso) e outra de exercício (cicloergômetro, 45 min, 50% VO2pico). A PA clínica, o débito cardíaco (DC), a resistência vascular periférica (RVP), o volume sistólico (VS), a frequência cardíaca (FC), a modulação autonômica cardíaca e vasomotora, a sensibilidade barorreflexa, o fluxo sanguíneo muscular, a capacidade vasodilatadora e as concentrações plasmáticas de noradrenalina e adrenalina foram medidos antes e após a intervenção em cada sessão. Além disso, a PA ambulatorial de 24 horas foi medida após as sessões e a concentração do metabólito da melatonina 6- sulfatoximelatonina produzida durante a noite anterior e posterior a cada sessão foi dosada. Os dados foram analisados pela ANOVA de 2 ou 3 fatores repetidos bem como pelo teste t ou teste de wilcoxon pareado e as associações foram calculadas pelas correlações de Pearson e Spearman. Foi aceito como significante P0,05. O exercício promoveu maior redução da PA sistólica pela manhã do que ao final do dia (-7±3 vs -3±4 mmHg, P<0,05), enquanto que a PA diastólica diminuiu de forma semelhante nestas duas fases do dia (-3±3 vs -3±3 mmHg, respectivamente). O DC diminuiu e a RVP tendeu a aumentar pós-exercício pela manhã, enquanto que estas variáveis não se modificaram pós-exercício ao final do dia (-460±771ml/min e +2,0±3,8 mmHg.min/l; +148±633ml/min e -1,4±2,8 mmHg.min/l, respectivamente). O VS diminuiu similarmente pós-exercício em ambas as fases do dia (- 12±15 vs. -9±10 ml, P<0,05), enquanto que a FC aumentou mais ao final do dia (+7±5 vs. +10±5 bpm, P<0,05). Isto ocorreu, devido ao exercício promover aumento do balanço simpatovagal (BF/AF) somente ao final do dia (+1,5±1,6, P<0,05), enquanto que a modulação vasomotora (BFPAS) pós-exercício diminuiu apenas pela manhã (-0,5±0,9 mmHg2, P<0,05). A sensibilidade barorreflexa espontânea, avaliada pelo do ganho médio de sequências positivas e negativas (SBR±) diminuiu pós-exercício nas duas fases do dia. O exercício não teve nenhum efeito sobre o fluxo sanguíneo e a capacidade vasodilatadora do braço, mas aumentou a capacidade vasodilatadora da perna apenas quando o exercício foi realizado ao final do dia (+116±172 ua, P<0,05). Nas medidas ambulatoriais, o exercício realizado ao final do dia reduziu a PA de sono e no período entre a 5 e 7ª hora pós-exercício. O exercício não teve nenhum efeito sobre os níveis de noradrenalina, adrenalina e 6-sulfatoximelatonina. Dessa forma, não houve correlações consistentes entre o efeito do exercício nos níveis hormonais e nas variáveis hemodinâmicas, autonômicas e ambulatoriais em nenhuma das fases do dia. Em conclusão, em pré-hipertensos, uma única sessão de exercício aeróbico reduz a PA pósexercício tanto quando o exercício é realizado pela manhã quanto ao final do dia, mas o maior efeito hipotensor é observado quando o exercício é realizado pela manhã para a PA sistólica. Este maior efeito hipotensor sistólico se deve à queda do DC pela manhã, que ocorre devido à diminuição do volume sistólico e menor aumento da FC pós-exercício nesta fase do dia, o que é provocado pelo menor aumento do balanço simpatovagal e se acompanha de menor aumento na capacidade vasodilatadora da musculatura ativa nesta fase do dia. O efeito hipotensor do exercício, no entanto, ao final do dia se reflete em redução da PA de sono pósexercício. Os efeitos do exercício aeróbico, realizado em diferentes fases do dia, sobre a PA clínica e ambulatorial e seus mecanismos hemodinâmicos, autonômicas e vasculares não se relacionam aos efeitos deste exercício sobre as catecolaminas e a produção de melatonina / Aerobic exercise is recommended for prehypertensive individuals to prevent hypertension development. An aerobic exercise bout promotes post-exercise hypotension, and previous studies with normotensive individuals reported that post-exercise hypotension is lower when exercise is conducted in the morning than in the evening. However, these studies have not included a control situation (without exercise) and only evaluated some hemodynamic determinants of this phenomenon. Thus, the aim of this study was to analyze and to compare blood pressure (BP) responses and their hemodynamic determinants and autonomic mechanisms after an aerobic exercise performed in the morning (9:00a.m) and the evening 6:30p.m), associating these results with the effects of this exercise in some neurohormonal markers of circadian rhythms. For this, 16 prehypertensive men underwent 4 experimental sessions conducted in random order: two in the morning and two in the evening. At each time of day, one control (rest) and one exercise (cycle ergometer, 45 min, 50% of VO2peak) sessions were performed. Clinic BP, cardiac output (CO), systemic vascular resistance (SVR), stroke volume (SV), heart rate (HR), cardiac autonomic modulation, vasomotor modulation, baroreflex sensitivity, muscle blood flow, vasodilation and plasma concentrations of norepinephrine and epinephrine were measured before and after the intervention in each session. In addition, ambulatory BP was measured for 24 hours after the experimental sessions and the concentration of melatonin metabolite 6-sulfatoxymelatonin produced during the sleep before and after each session was assessed. Data were analyzed by 2 or 3-way ANOVA for repeated measures as well as by paired t test or Wilcoxon test, and the associations between variables were calculated by Pearson and Spearman correlations. P 0.05 was accepted as significant. Exercise produced a greater systolic BP reduction in the morning than the evening (-7 ± 3 -3 ± 4 mmHg, P<0.05), while the diastolic blood pressure decreased similarly in both times of day (-3±3 vs -3±3 mmHg, respectively, P<0.05). CO decreased and SVR tended to increased after exercise in the morning, while these variables did not change after exercise in the evening (-460 ± 771ml/min and +2.0 ± 3.8 mmHg.min/l; +148 633ml/min ± 2.8 and -1.4 ± mmHg.min/l , respectively). VS decreased similarly after exercise in both times of day (-12 ± 15 vs -9 ± 10 ml, P<0.05), while the HR increased more in the evening (+7 ± 5 vs +10 ± 5 bpm, P<0.05). This occurred because exercise increased sympathovagal balance only in the evening (+1.5 ± 1.6, P<0.05), whereas vasomotor modulation decreased only after exercise performed in the morning (-0.5 ± 0.9 mmHg2, P<0.05). Spontaneous baroreflex sensitivity, measured by the average gain of positive and negative sequences (± SBR) decreased after the exercise in both times of day. The exercise did not affect arm blood flow and vasodilatory capacity, but increased leg vasodilation when exercise was performed in the evening (+116 ± 172 au, P<0.05). In regard to ambulatory measures, the exercise performed in the evening reduced asleep BP and BP measured 5-7hr post-exercise. The exercise did not have any effect in the norepinephrine, epinephrine and 6- sulphatoxymelatonin. Thus, there was not consistent correlation between the effect of exercise in hormone levels and in hemodynamic, autonomic and ambulatory responses. In conclusion, in prehypertensives, a single bout of aerobic exercise reduces post-exercise BP regardless if the exercise is performed in the morning or in the evening, however a greater hypotensive effect is observed in the morning for systolic BP. This greater systolic hypotensive effect is due to the decrease in CO in the morning, related to a decrease in SV and a lower increase in HR after the exercise performed in the morning, which is caused by a lower increase in sympathovagal balance and is accompanied by a smaller increase in active muscles vasodilatory capacity in the morning. The hypotensive effect of evening exercise leads to a reduction in asleep BP. The effects of exercise, performed at different times of day, on postexercise clinic and ambulatory BP as well in its hemodynamic, autonomic and vascular determinants are not related to the effects of this exercise in catecholamines and melatonin production

A pós-menopausa é marcada por alterações fisiológicas hemodinâmicas e metabólicas. A terapia de reposição estrogênica é uma forma de amenizar as conseqüências da deficiência hormonal e o exercício físico contribui significativamente para a redução do risco cardiovascular. O objetivo desse estudo foi avaliar em mulheres pós-menopausadas os efeitos isolados e associados da terapia oral estrogênica (TRH) e do treinamento físico aeróbio (TF) nas respostas hemodinâmicas e neurais basais e durante os exercícios com handgrip. Quarenta e cinco mulheres (51±3 anos), histerectomizadas, com e sem ovários, saudáveis, realizaram uma sessão experimental e, posteriormente foram divididas em 4 grupos SED-PLA (n=11), SED-TRH (n=14), TF-PLA (n=12) e TF-TRH (n=8). Os grupos TRH e receberam valerato de estradiol 1mg/dia; PLA receberam placebo; TF, realizaram exercício aeróbio em cicloergômetro por 50 minutos, 3 vezes por semana e SED permaneceram sedentárias. Todas as voluntárias participaram de uma segunda sessão experimental após 6 meses de acompanhamento. Nas sessões experimentais foram avaliadas a atividade nervosa simpática periférica (ANSP - microneurografia), pressão arterial, freqüência cardíaca (FC - método oscilométrico Dixtal no membro inferior), fluxo sangüíneo do antebraço (FSA - pletismografia) em um período basal e durante exercícios estático e dinâmico com handgrip a 30% da força de contração máxima. Para análise estatística foi utilizada ANOVA. O TF isoladamente diminuiu ANSP de 40±7 a 34±4 impulsos/min, (P=0,01) e aumentou FSA de 1,92±0,96 a 2,65±1,34 ml(min.100ml), P=0,03 no período basal. TRH e TF associados reduziram a FC no período basal de 65±8 para 62±7 bpm (P=0,01) e durante o exercício estático e dinâmico com handgrip. A TRH de maneira isolada ou associada ao TF diminuiu as respostas de FC durante os exercícios estático e dinâmico com handgrip. Em conclusão, as intervenções de maneira isolada ou associada promovem alterações hemodinâmicas e neurais que podem contribuir para redução do risco cardiovascular de mulheres pós-menopausadas saudáveis. / The post-menopause is marked by physiological hemodynamic and metabolic changes. The estrogen replacement therapy is a way to reduce the consequences of hormone deficiency and physical exercise contributes significantly to the reduction of cardiovascular risk. The aim of this study was to evaluate in post-menopausal women the isolated and associated effects of oral estrogen therapy (TRH) and physical training (TF) in the neural and hemodynamic responses during baseline and \"handgrip\" exercises. Forty-five women (51 ± 3 years), hysterectomized, with or without ovaries, healthy, participated of an initial session and then they were divided into 4 groups SEDPLA (n = 11), SED-TRH (n = 14), TF-PLA (n = 12) and TF-TRH (n = 8). The TRH groups received estradiol valerate 1 mg / day; PLA placebo; TF, performed aerobic exercise on a cycle ergometer for 50 minutes, 3 times a week and SED remained sedentary. All subjects participated in a second experimental session after 6 months of follow-up. In the experimental sessions peripheral sympathetic nerve activity (ANSP - microneurography), blood pressure, heart rate (FC - oscillometry - Dixtal lower limb), forearm blood flow (FSA - plethysmography) were evaluated at the baseline period and during static and dynamic \"handgrip\" exercises at 30% of the maximum force. ANOVA was used for the statistica analysis. The TF alone decreased ANSP from 40 ± 7 to 34 ± 4 bursts/min, P = 0.01 and increased FSA 1.92 ± 0.96 to 2.65 ± 1.34 ml (min.100ml), P = 0.03 at the baseline. The association of TRH and TF reduced HR at the baseline from 65 ± 8 to 62 ± 7 bpm (P=0.01) and during exercise with static and dynamic \"handgrip\". HRT alone or associated with TF decreased the HR responses during static and dynamic \"handgrip exercises. In conclusion, the interventions alone or in an associated way promote neural and hemodynamic changes that may contribute to cardiovascular risk reduction in healthy postmenopausal women.

Esta tese avaliou as respostas fisiológicas à hiperinsulinemia aguda em mulheres na pós-menopausa, verificando os efeitos isolados e associados da terapia hormonal (TH) e do treinamento aeróbico (TF) sobre estas respostas. Assim, 31 mulheres histerectomizadas, saudáveis e na pós-menopausa foram divididas, aleatoriamente e de forma duplo cega, nos grupos: PLA-CO(n=7), TH-CO(n=6), PLA-TF(n=10), TH-TF(n=8). Os grupos TH receberam valerato estradiol (1 mg/dia) e os PLA, placebo. Os grupos TF treinaram em cicloergômetro, 3x/sem em intensidade moderada e os CO permaneceram sedentários. Antes e após 6 meses, foi realizado um clampeamento euglicêmico/hiperinsulinêmico. Em resposta à hiperinsulinemia, houve aumento das catecolaminas plasmáticas, da modulação simpática cardíaca, da pressão arterial sistólica, da frequência cardíaca e do fluxo sanguíneo. Após 6 meses, o TF aumentou a sensibilidade à insulina e reduziu o aumento da noradrenalina durante a hiperinsulinemia. Tanto isoladamente quanto em associação, o TF e a TH impediram a redução do aumento do fluxo sanguíneo durante a hiperinsulinemia, o que foi observado no grupo PLA-CO. Além disso, quando associadas, estas condutas reduziram o aumento da adrenalina durante a hiperinsulinemia. Concluindo: em mulheres pós-menopausadas saudáveis, a hiperinsulinemia aguda aumentou a atividade simpática e promoveu vasodilatação, levando ao aumento da pressão arterial sistólica e da frequência cardíaca, sem alterar a pressão diastólica, respectivamente. O TF aumentou a sensibilidade à insulina, diminuindo a ativação simpática e mantendo a vasodilatação induzida pela hiperinsulinemia, enquanto que a TH teve o mesmo efeito sobre a vasodilatação, sem alterar a sensibilidade à insulina. A associação das duas condutas teve pouco efeito aditivo / This thesis evaluated the physiological responses to acute hyperinsulinemia in post-menopausal women, analyzing the isolated and combines effects of hormone therapy (HT) and aerobic training (AT) on these responses. Thus, 31 healthy, hysterectomized postmenopausal women were randomly divided (in a double-blinded manner) into groups: PLA-CO(n=7), HT-CO(n=6), PLA-AT(n=10), HT-AT(n=8). HT groups received valerato estradiol (1 mg/day) while PLA groups received placebo. AT groups trained on cycle ergometer, 3x/week at moderate intensity, while CO groups stayed sedentary. Before and after 6 months, an euglycemic hyperinsulinemic clamp were performed. Hyperinsulinemia increased plasma catecholamines, sympathetic cardiac modulation, systolic blood pressure, heart rate, and blood flow. After 6 months, AT increased insulin sensitivity and reduced insulin induced increase in norepinephrine. AT and HT, applied alone or together, abolished the decline in insulin induced increase in blood flow that was observed in PLA-CO. Besides, the association of both interventions decreased insulin induced increase in epinephrine. In conclusion: in healthy postmenopausal women, acute hyperinsulinemia increased sympathetic activity but produced vasodilation, which resulted in an increase in systolic blood pressure and heart rate, with no change in diastolic blood pressure, respectively. AT increased insulin sensitivity, decreasing sympathetic activation and maintaining vasodilatory response during hyperinsulinemia, while HT had the same effect on vasodilation without changing insulin sensitivity. The association of both interventions had minor addictive effects