Leydig and Sertoli cell function in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion: a case-control study

Abstract BACKGROUND: Because normal male sexual differentiation is more complex than normal female sexual differentiation, there are more cases of disorders of sex development (DSDs) with 46,XY karyotype that have unclear etiology. However, Leydig and Sertoli cell markers are rarely used in distinguishing such individuals. OBJECTIVES: To evaluate the function of Leydig and Sertoli cells in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion. STUDY DESIGN AND SETTING: Case-control study with 77 patients, including eight with partial androgen insensitivity syndrome, eight with 5α-reductase deficiency type 2 (5ARD2) and 19 with idiopathic 46,XY DSD, and 42 healthy controls, from the Interdisciplinary Study Group for Sex Determination and Differentiation (GIEDDS), at the State University of Campinas (UNICAMP), Campinas, Brazil. METHODS: Baseline levels of gonadotropins, anti-Müllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), testosterone and dihydrotestosterone in cases, and AMH, inhibin B, and INSL3 levels in controls, were assessed. RESULTS: There was no significant difference in age between cases and controls (P = 0.595). AMH and inhibin B levels were significantly lower in cases than in controls (P = 0.031 and P < 0.001, respectively). INSL3 levels were significantly higher in cases than in controls (P = 0.003). Inhibin B levels were lower in 5ARD2 patients (P = 0.045) and idiopathic patients (P = 0.001), in separate comparisons with the controls. CONCLUSION: According to our findings, we can speculate that inhibin B levels may be used to differentiate among DSD cases.

The effect of testosterone replacement on intramedullary, inguinal and visceral fat in ovariectomized rats / Efeito da reposição de testosterona na gordura intramedular, inguinal e visceral em ratas ovariectomizadas

Abstract Objective The present article aims to evaluate the impact of testosterone treatment on the expansion of visceral, subcutaneous and intramedullary adipose tissue of ovariectomized rats and the visceral and subcutaneous fat expression of peroxisome proliferator-activated receptors (PPARs) gamma. Methods In total 48 female Wistar rats were castrated and randomly divided into 6 treatment groups: group E2 was submitted to estradiol 5 μg/day; group T, to testosterone 5 μg/day; group E2+ T, to estradiol 5 μg/day + testosterone 5 μg/day; group TT, to testosterone 30 μg/day; group E2+ TT, to estradiol 5 μg/day+ testosterone 30 μg/day; and placebo was administered to group P. After 5 weeks, the rats were euthanized, the inguinal and visceral adipose tissues were harvested, weighted, and had their PPAR gamma expression evaluated by reverse transcription quantitative polymerase chain reaction (RTqPCR). The right femurs were harvested and histologically prepared to performthe number count of the intramedullary adipocytes. Results The expansion of visceral fat tissue was much higher in the TT group when compared with other treated groups (p < 0.001). The TT group also showed a higher expansion of inguinal fat (p < 0.01), and groups E2 +T and E2+ TT presented lower growth compared to the P group (p < 0.01). The number of femur intramedullary adipocytes only showed significant differences between groups TT and E2 + TT (p < 0.05). The expression of PPAR gamma showed no differences among the groups. Conclusion The use of testosterone in high doses leads to an important expansion in both visceral and inguinal adipose tissues. Association with estradiol exerts an expansion-repressive effect on the visceral and inguinal adipose tissues.

Resumo Objetivo Este artigo tem como objetivo avaliar o impacto do tratamento com testosterona na expansão dos tecidos adiposos visceral, subcutâneo e intramedular de ratas ovariectomizadas e a expressão de receptores ativados por proliferadores de peroxissoma (RAPPs) gama nas gorduras visceral e subcutânea. Métodos No total, 48 ratas Wistar foram castradas e divididas aleatoriamente em 6 grupos de tratamento: o grupo E2 recebeu estradiol 5 μg/dia; o grupo T, testosterona 5 μg/dia; o grupo E2 + T, estradiol 5 μg/dia + testosterona 5 μg/dia; o grupo TT, testosterona 30 μg/dia; o grupo E2 + TT, estradiol 5 μg/dia + testosterona 30 μg/dia; e o grupo P recebeu placebo. Após 5 semanas, as ratas foram submetidas a eutanásia, o tecido adiposo inguinal e visceral foi coletado, pesado, e se avaliou a expressão dos RAPP gama por reação em cadeia da polimerase via transcriptase reversa quantitativa (RCP-TRq). Os ossos do fêmur direito foram colhidos e processados histologicamente para contagem de números de adipócitos intramedulares. Resultados A expansão do tecido adiposo visceral foi muito maior no grupo TT quando comparado a outros grupos tratados (p < 0,001). O grupo TT também apresentou maior expansão da gordura inguinal (p < 0,01), e os grupos E2 +T e E2 + TT apresentaram menor crescimento em relação ao grupo P (p < 0,01). O número de adipócitos intramedulares no fêmur mostrou apenas diferenças significativas entre os grupos TT e E2 + TT (p < 0,05). A expressão de RAPP gama não mostrou diferenças entre os grupos. Conclusão O uso de testosterona emaltas doses leva a uma importante expansão nos tecidos adiposos visceral e inguinal. A associação com o estradiol exerce um efeito repressivo de expansão nos tecidos adiposos visceral e inguinal.

Imbalance in the diurnal salivary testosterone/cortisol ratio in men with severe obstructive sleep apnea: an observational study / Desequilíbrio na proporção salivar diurna de testosterona/cortisol em homens com apneia obstrutiva do sono grave: um estudo observacional

ABSTRACT INTRODUCTION: The complex relationship between sleep disorders and hormones could lead to alterations in the production of cortisol and testosterone in obstructive sleep apnea (OSA) patients. OBJECTIVE: The purpose of this study was to determine the diurnal trajectories of salivary free-testosterone, free-cortisol and their ratio (T/C). METHODS: Ten subjects newly diagnosed with OSA, based on nocturnal polysomnography evaluation and excessive daytime sleepiness, and seven matched controls were consecutively recruited. Cortisol and testosterone were measured in salivary samples collected upon awakening, at noon and in the evening. The psychometric evaluation of anxiety/depression and referred sexual function disturbances was performed to evaluate the presence of neuropsychological comorbidities. RESULTS AND CONCLUSION: The main finding was that OSA subjects displayed hypocortisolism upon awakening and a significant reduction in testosterone concentration in the evening in comparison with the control group, which has maintained the physiological testosterone and cortisol diurnal fluctuation, with higher hormone concentrations in the morning and lower concentrations in the evening. The use of data from multiple diurnal measurements rather than a single point allowed the detection of T/C ratio changes of opposite signs at the beginning and end of the day: the OSA subjects had a higher T/C ratio than the controls in the morning, while their T/C ratio was significantly lower than that of the controls in the evening. The imbalances in the anabolic-catabolic diurnal equilibrium suggest that OSA is associated with a dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, potentially an underlying cause of some of the neuropsychological comorbidities observed in OSA patients.

Resumo Introdução: A relação complexa entre os distúrbios do sono e os hormônios pode levar a alterações na produção de cortisol e testosterona em pacientes com Apneia obstrutiva do sono (AOS). Objetivo: O objetivo deste estudo foi determinar as curvas diurnas de testosterona e cortisol livres na saliva e sua proporção (razão T/C). Método: Dez indivíduos recém-diagnosticados com AOS com base na avaliação por polissonografia noturna e sonolência diurna excessiva e sete controles pareados foram recrutados, consecutivamente. Cortisol e testosterona foram medidos em amostras de saliva coletadas ao acordar, ao meio-dia e à noite. A avaliação psicométrica dos distúrbios de ansiedade/depressão e função sexual mencionados foi realizada para detectar a presença de comorbidades neuropsicológicas. Resultados: O achado principal foi que os indivíduos com AOS apresentam hipocortisolismo ao acordar e uma redução significante na concentração de testosterona à noite, em comparação com o grupo controle, que manteve a variação fisiológica diurna de testosterona e cortisol com concentrações hormonais mais elevadas pela manhã e concentrações mais baixas durante a noite. O uso de dados de várias mensurações diurnas, em vez de uma única mensuração, permitiu detectar as alterações na razão T/C de sinais opostos no início e no final do dia: os indivíduos com AOS apresentaram razão T/C maior que os controles na parte da manhã, enquanto que a razão T/C foi significantemente inferior à dos controles durante a noite. Conclusão: Os desequilíbrios no balanço anabólico-catabólico diurno sugerem que a AOS está associada a uma desregulação dos eixos hipotálamo-hipófise-adrenal e hipotálamo-hipófise-gonadal, potencialmente a causa subjacente de algumas das comorbidades neuropsicológicas observadas em pacientes com AOS.

Asociación entre niveles de testosterona, sensibilidad a la insulina, adiposidad y parámetros lipídicos en hombres / Association between testosterone levels, insulin sensitivity, adiposity and lipid parameters in men

Introducción: Evidencias sugieren que la testosterona interviene en la regulación del metabolismo de la glucosa y los lípidos.Objetivo: determinar la relación entre los niveles de testosterona y la sensibilidad a la insulina, la adiposidad y los parámetros del metabolismo lipídico en hombres.Métodos: estudio transversal y descriptivo en 225 hombres, entre 35 y 60 años, con y sin trastornos de la tolerancia a la glucosa. Se midieron: talla, peso, circunferencias de la cintura y de la cadera. Se realizaron determinaciones de insulina, glicemia, testosterona, colesterol, HDL-colesterol, LDL-colesterol y triglicéridos. Se determinaron índices de sensibilidad y resistencia a la insulina.Resultados: se encontró una correlación negativa entre los niveles de testosterona y la resistencia a la insulina, y los parámetros de adiposidad explorados (índice de masa corporal, circunferencias abdominal y de la cadera, índice cintura/cadera). El nivel de testosterona fue menor en los sujetos con hipertrigliceridemia. En los sujetos con trastornos de la tolerancia, se encontró un aumento significativo de la frecuencia de obesidad abdominal en presencia de valores bajos de testosterona.Conclusiones: existe una asociación directa entre los niveles de testosterona y la sensibilidad a la insulina en la población estudiada. La disminución de los niveles de testosterona en presencia de los desórdenes asociados al síndrome metabólico, sugiere la indicación de una evaluación metabólica temprana a los pacientes con hipogonadismo(AU)

Introduction: Evidence suggests that testosterone participates in the regulation of glucose and lipid metabolism.Objective: determine the relationship between testosterone levels and insulin sensitivity, adiposity and metabolism parameters in men.Methods: a descriptive cross-sectional study was conducted of 225 men aged 35-60 with and without glucose tolerance disorders. The variables measured were height, weight, and waist and hip circumference. Determinations were made for insulin, glycemia, testosterone, cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. Insulin sensitivity and resistance were also determined.Results: a negative correlation was found between testosterone levels/insulin resistance and the adiposity parameters considered (body mass index, waist and hip circumference and waist to hip ratio). Testosterone levels were lower in subjects with hypertriglyceridemia. Patients with tolerance disorders showed a significant increase in the frequency of abdominal obesity in the presence of low testosterone values.Conclusions: a direct relationship was found between testosterone levels and insulin sensitivity in the population studied. Reduced testosterone levels in the presence of disorders associated to metabolic syndrome suggest the need for an early metabolic assessment of patients with hypogonadism(AU)

Response of male mice to odours of female mice in different stages of oestrous cycle: Self-grooming behaviour and the effect of castration.

The behavioural assays were carried out in a Y-maze wherein intact, castrated and testosterone-treated male mice were exposed to oestrus and non-oestrus urine samples. The intact male mice investigated more frequently and spent more time in the Y-maze arm with oestrus urine than in that with non-oestrus urine. In contrast, the castrated mice were not attracted to oestrus urine, whereas testosterone-treated mice showed preference for oestrus urine. The rate of self-grooming was higher in intact males in case of exposure to oestrus urine while the rate was lower with respect to non-oestrus urine. However, castrated mice exhibited less self-grooming behaviour which was partially restored by testosterone treatment. The results suggest that self-grooming behaviour is an indicator of detection and discrimination of oestrus by males, and supports the androgen role in male chemosensory ability to discriminate between oestrus and non-oestrus female odours.

Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency - a prospective study

INTRODUCTION: Male testosterone deficiency is associated with bad sexual function and quality of life (QoL). The aim of this study was to determine whether a daily dose of 25 mg clomiphene citrate (CC) is effective in stimulating the endogenous testosterone production pathway and to address the applicability of this medication as a therapeutic option for symptomatic hypogonadism. MATERIALS AND METHODS: This was a prospective study. Men with low sexual desire and testosterone levels (T) below 400 ng/dL were selected to receive CC. Blood samples were obtained to determine baseline measurements of serum T, estradiol, LH, lipid profile and fasting plasma glucose. Each patient was treated with a daily dose of 25 mg CC for at least 3 months. Patients were asked if they experienced any side effects related to the use of CC and if they experienced any improvement in their sexual profile. Paired samples T-test was utilized to analyze responses to therapy. RESULTS: Our cohort consisted of 125 men with hypogonadism and low libido. Mean age was 62 years (± 11.1 years). Serum T levels ranged from 309 ng/dL (baseline, mean value) to 642 ng/dL (3 months after CC initiation, mean value) (p < 0.001). Serum cholesterol levels ranged from 197 to 186 mg/dL (p = 0.003). There were no statistically significant differences when comparing pre and post-treatment HDL-Cholesterol, triglycerides, fasting plasma glucose and prolactin. All men reported improvements in the post-treatment QoL scores. No serious adverse events were recorded. CONCLUSIONS: The CC was effective in stimulating the endogenous production of testosterone. A lower level of total cholesterol was verified after three months of treatment. This medication should be considered as a therapeutic option for some patients with symptomatic male testosterone deficiency.

Clomiphene fails to revert hypogonadism in most male patients with conventionally treated nonfunctioning pituitary adenomas / Clomifeno não reverte o hipogonadismo na maioria dos homens com adenomas pituitários não funcionais tratados de forma convencional

OBJETIVE: To evaluate the effect of clomiphene in men with hypogonadism and conventionally treated nonfunctioning pituitary adenomas (NFPA). PATIENTS AND METHODS: Open label, single-arm, prospective trial. Nine hypogonadal men (testosterone < 300 ng/dL and low/normal LH) with previously treated NFPA. Clomiphene (50 mg/day orally) for 12 weeks. Testosterone, estradiol, LH, FSH, prolactin and erectile function were evaluated before and after 10 days, 4, 8 and 12 weeks of clomiphene treatment. RESULTS: After clomiphene treatment, testosterone and erectile function improved in only one patient. In the remaining eight patients, testosterone levels decreased whereas LH, FSH, and estradiol remained unchanged. Insulin sensitivity increased in unresponsive patients. CONCLUSIONS: Compared with hypogonadal men with prolactinomas under dopaminergic therapy, clomiphene treatment failed to restore normal testosterone levels in most patients with conventionally treated NFPA.

OBJETIVO: Avaliar o efeito do clomifeno em homens com hipogonadismo e adenoma hipofisário não funcionante (NFPA) previamente tratados. PACIENTES E MÉTODOS: Aberto, braço único, prospectivo. Nove homens hipogonádicos (testosterona < 300 ng/dL e LH normal/baixo) com NFPA previamente tratados. Clomifeno (50 mg/dia oral) por 12 semanas. Testosterona, estradiol, LH, FSH, prolactina e função erétil foram avaliados antes e após 10 dias, 4, 8 e 12 semanas de clomifeno. RESULTADOS: Após clomifeno, a testosterona e a função erétil melhoraram em um paciente. Em outros oito pacientes, os níveis de testosterona reduziram enquanto os níveis de LH, FSH, e estradiol permaneceram inalterados. A sensibilidade à insulina aumentou nos não respondedores. CONCLUSÕES: Em contraste com homens hipogonádicos com prolactinomas tratados com agonistas dopaminérgicos, a maioria dos hipogonádicos com NFPA falha em restaurar os níveis de testosterona durante o uso de clomifeno.

effect of gender differences on the response of IL-6, IL-5, cortisol to single session of circuit resistance exercise in elite handball players

Very few studies have been done with regard to the gender differences of the immune system in responding to exercise, which generally do not control women's period cycle. Considering that levels of sex hormones differ during the menstrual cycle this study investigates the influence of gender differences on the response of IL-6, IL-15, cortisol and sex hormone to a single session of circuit resistance exercise in both male and female elite Handball players, while controlling CHECK on the women menstrual period cycles. The participants of the study were 12 elite Handball players, 5 men and 7 women. The circuit resistance exercise included 10 min warming, performing chest press, leg press, leg press, abdominal crunch, literal pull down, leg extension in 3 sets with 10 repetitions with 60% 1RM and 10 min cooling down. Pre, immediately and 2 hours post exercise, the blood samples were collected in order to measure IL-6, IL-15, cortisol, testosterone and estrogen levels. Results indicated that IL-6 concentration was different in the two groups after the exercise, which showed an increase in men and a decrease in women. There was no significant difference between the two groups IL-15 levels, but significant difference was observed between the two groups in cortisol, testosterone and estrogen levels. A single session of circuit resistance exercise resulted in different responses in the Immune system of men, in comparison with women

Modalidades de tratamento para sintomas sexuais da menopausa / Types of treatment for sexual symptoms of menopause

As mudanças no epitélio e na musculatura vaginal decorrentes das alterações hormonais, acrescidas da diminuição na lubrificação genital provocam secura vaginal e, muitas vezes, dispareunia, condições que têm sido responsabilizadas pelo comprometimento da atividade sexual feminina na transição menopáusica. Porém, há várias outras condições a se considerar, como os sentimentos, conflitos e disfunção sexual do parceiro, bem-estar subjetivo e a incidência e intensidade dos sintomas menopausais. Devido à multiplicidade de fatores envolvidos no comprometimento da qualidade de vida da mulher climatérica, a oportunidade de abordar suas dificuldades, inclusive as sexuais, é parte fundamental na assistência à saúde. Para investigar as dificuldades sexuais, o profissional de saúde precisa identificar a qualidade do estímulo, o contexto sexual, os impedimentos para o casal conseguir prazer erótico, além de buscar soluções, principalmente por meio de informações relevantes. A psicoterapia pode ter um aspecto mais psicoeducativo, voltado à sensibilização para o reconhecimento das partes do corpo mais responsivas ao estímulo e consciência dos sinais fisiológicos da excitação e do orgasmo. Em relação à testosterona, as recomendações atuais sugerem decisão individualizada, com informações sobre riscos e benefícios, devendo ser considerados as indicações e acompanhamento cuidadoso da paciente. Os fitoestrogênios disponíveis em alimentos e extratos de soja não melhoram a frequência nem amenizam a gravidade dos sintomas menopausais, embora mostrem alguma tendência de melhora discreta, sem significância estatística. Na atualidade, a psicoterapia, a fisioterapia, práticas esportivas e cuidados com a saúde geral têm constituído valiosos aliados no enfrentamento da sintomatologia da transição menopáusica.

Rol protector del 17ß-Estradiol y la testosterona en la apoptosis del músculo esquelético / Protective role of 17ß-Estradiol and testosterone in apoptosis of skeletal muscle

La sarcopenia, pérdida de masa y fuerza del músculo esqueléico, es una condición frecuente durante el envejecimiento. Conduce a incapacidad motora resultando en internación y mortalidad. Puesto que los niveles de estrógenos y/o testosterona disminuyen con la edad, la sarcopenia se ha asociado al déficit de estas hormonas. Aunque los mecanismos moleculares involucrados en esta patología no están totalmente dilucidados, existen evidencias indicando que la apoptosis es en parte responsable de la pérdida de miocitos en la adultez. Previamente demostramos que el 17ß-estradiol (E2) inhibe la apoptosis en la línea celular C2C12 de músculo esquelético a través de PI3K/Akt, MAPKs, HSP27 y receptores estrogénicos (ERs) con localización no clásica. Usando siRNAs específicos para silenciar las isoformas del ER, comprobamos que el E2 activa ERK involucrando a ERa, mientras que la activación de p38 MAPK es independiente de ERs. Confirmamos que el E2 puede inhibir la apoptosis a través de las MAPKs en cultivos primarios de músculo esquelético de ratón. Al igual que la E2, la testosterona bloquea la apoptosis. Las alteraciones morfológicas típicas de la apoptosis como fragmentación nuclear, desorganización del citoesqueleto, reorganización/disfunción mitocondrial y liberación de citocromo c, inducidos por H2O2 fueron suprimidas al preincubar las células con testosterona. Se requieren investigaciones adicionales para establecer un paralelismo entre los mecanismos de acción de ambas hormonas, que podrían estar implicados en patologías musculares asociadas a apoptosis. Los datos presentados en este estudio profundizan el conocimiento de las bases moleculares de la sarcopenia relacionada con estados de déficit de hormonas sexuales.

Epidermal growth factor receptors, testosterone levels and parotid gland changes in rats infected with Trypanosoma cruzi

It has been demonstrated that parotid glands of rats infected with Trypanosoma cruzi present severe histological alterations; changes include reduction in density and volume of the acini and duct systems and an increase in connective tissue. We evaluated the association between morphological changes in parotid glands, circulating testosterone levels and epidermal growth factor receptor (EGF-R) expression in experimental Chagas disease in rats. Animals at 18 days of infection (acute phase) showed a significant decrease in body weight, serum testosterone levels and EGF-R expression in the parotid gland compared with a control group. Since decreases in body weight could lead to a reduction in circulating testosterone concentration, we believe that the reduction in EGF-R expression in parotid glands of infected rats is due to alterations in testosterone levels and atrophy of parotid glands is caused by changes in EGF-R expression. Additionally, at 50 days (chronic phase) of infection parotid glands showed a normal histological aspect likely due to the normalization of the body weight. These findings suggest that the testosterone-EGF-R axis is involved in the histological changes.

Modificaciones del perfil hormonal sexual como resultado de la administración conjunta de dos sustancias que inhiben el metabolismo de la testosterona / Sexual hormonal profile modifications as a result of the join administration of two substances inhibitors of the testosterone metabolism

Con este trabajo se pretendió ver el efecto sobre el perfil hormonal sexual y en especial sobre la concentración de testosterona después de administrar dos sustancias que bloquean por diferentes mecanismos la degradación de ésta. Además comprobar, utilizando la técnica gases-combustión-espectrometría de isótopos estables (gc-cirms), si la testosterona que se acumula en el organismo por estas inhibiciones se debe simplemente al bloqueo de los mecanismos de degradación o a que alguno de los compuestos administrados entra en la ruta metabólica como precursor para aumentar su producción. Con tal propósito, se estudiaron los efectos que tenía el inhibidor de la aromatasa 3, 6, 17 androstenetriona (6-Oxo) sobre el perfil hormonal sexual de dos voluntarios sanos y confirmamos mediante el análisis isotópico la participación de esta sustancia en la ruta de producción de testosterona mediante el estudio de sus metabolitos mayoritarios de excreción: androsterona y etiocolanolona. Luego se estudió el efecto que tenía la administración de este inhibidor en combinación con un inhibidor del citocromo p-450 (6’, 7’, dihidroxibergamotin-dhb) en otros dos voluntarios. En los dos experimentos se observó un aumento del perfil hormonal, especialmente de la concentración de dehidroepiandrosterona (dhea) y testosterona, explicando por qué se promocionan en el comercio este tipo de mezclas para aumentar la masa muscular y, en consecuencia, la apariencia física.

This work aimed to see the effect on the sexual hormonal profile and in particular on the concentration of testosterone after administration of two different substances that block the mechanisms of its degradation. In addition check, using the technique of stable isotopes (gc-c-irms), if the testosterone that accumulates in the body by these inhibitions is due simply to the blocking of the mechanisms of degradation or any of the compounds administered go into the route as a metabolic precursor to increase its production. To accomplish this we studied the effects that initially had the aromatase inhibitor 3, 6, 17 androstenetriona (6-Oxo) on the sexual hormonal profile of two healthy volunteers and confirmed, by the isotopic analysis, that this substance participate in the road testosterone production by studying its major metabolites of excretion: Androsterone and Ethiocholanolone. Subsequently we studied the effect of the administration of this inhibitor in combination with an inhibitor of cytochrome p-450 (6 ‘, 7’, dihidroxibergamotin-dhb) in two other volunteers. In both experiments showed an increase in the hormonal profile especially in the concentration of dehydroepiandrosterone (dhea) and testosterone, explaining the reason of why such mixtures are promoted to increase muscle mass and thus the physical appearance.

Concentrações plasmáticas de testosterona, triiodotironina (T3) e tiroxina (T4) em bodes submetidos ao estresse calórico / Plasma concentrations of testosterone, triiodothyronine (T3), and thyroxine (T4) in bucks submitted to heat stress

Para verificar o efeito do estresse calórico (EC) nas concentrações plasmáticas de testosterona, triiodotironina (T3) e tiroxina (T4), oito bodes, das raças Saanen (n=4) e Alpina (n=4), foram mantidos em câmara bioclimática, sob condições de termoneutralidade (13,0ºC a 26,7ºC) durante 30 dias e, após um período (60 dias) de descanso, submetidos ao EC (23,7ºC a 34,0ºC) por 30 dias. Para minimizar as variações sazonais nos perfis hormonais devido ao fotoperíodo, durante toda fase experimental, incluindo a de adaptação em condições de termoneutralidade (30 dias), o fotoperíodo foi controlado utilizando-se alternância de dias longos (16h de luz e 8h de escuro) e de dias curtos (8h de luz e 16h de escuro) a cada 30 dias. As amostras de sangue foram coletadas duas vezes por semana durante cinco semanas. No conjunto das raças, o EC não influenciou (P>0,05) as concentrações de testosterona (1,8±0,2 vs 1,3±0,2ng/ml) e nem a de T4 (52,7±2,8 vs 50,0±2,8ng/ml). Houve declínio (P<0,01) das concentrações de T3 nos animais submetidos ao experimento (1,3±0,1 vs 1,0±0,1ng/ml), mas a redução foi observada somente nos bodes Saanen. Em ambas as raças, as concentrações de T3 e T4 variaram (P<0,01) conforme o dia da coleta das amostras de sangue. O EC foi suficiente para produzir uma resposta fisiológica com redução das concentrações plasmáticas de T3 em bodes das raças Saanen, mas não da raça Alpina, assim como não foi capaz de alterar os níveis plasmáticos de testosterona e nem de T4.

To verify the effect of heat stress (HS) on plasma testosterone, triiodothyronine (T3), and thyroxine (T4) concentrations, eight Saanen (n=4) and Alpine Brown (n=4) bucks were kept in climate chamber under thermal neutral conditions (13.0ºC to 26.7ºC) for 30 days. After a resting period (60 days), the same bucks were submitted to heat stress (23.7ºC to 34.0ºC) for another 30 days. To neutralize the seasonal variations of hormonal profiles throughout the period, the photoperiod was controlled every 30 days altering long (16 hours of light and 8 hours of darkness) and short days (8 hours of light and 16 hours of darkness). The blood samples were collected twice a week during five weeks. In both breeds, there was no effect of HS (P>0.05) on plasma concentrations of testosterone (1.8±0.2 vs 1.3±0.2ng/ml) and T4 (52.7±2.8 vs 50.0±2.8ng/ml). There was a decline (P<0.01) of plasma T3 concentrations (1.3±0.1 vs 1.0±0.1ng/ml) after HS treatment, but this reduction was only evident in Saanen bucks. In both breeds, the plasma concentrations of T3 and T4 varied (P<0.01) according to the day of blood sample collection. The HS was sufficient to provoke a physiological response with reduction of plasma concentrations of thyroid hormones mainly of T3 in Saanen bucks, but not in Alpine ones. The HS did not affect the plasma testosterone and T4 levels.

Effect of malathion on reproductive system of male rats.

The pesticides are one of the most potentially harmful chemicals liberated in the environment in an unplanned manner Malathion is widely used as a potent pesticide in many countries and has been shown to produce some adverse health effects. A study was conducted to asses the effects of malathion on the male reproductive system of wistar rats. The pesticide was administered to rats orally at dose levels of 50, 150 and 250 mg/kg/body wt/day for 60 days. In comparison to the control rats, there was a significant reduction in the weight of testes, epididymis, seminal vesicle and ventral prostate. Testicular and epididymal sperm density were decreased in the animals treated with malathion. Pre and post fertility test showed 80% negative results after treatment Biochemical profile of the testis revealed a significant decline in the contents of sialic acid and glycogen. Whereas a significant increase in the protein content of testis and testicular cholesterol was observed. The activity of testicular enzyme acid phosphatase increased significantly while decreased alkaline phosphatase activity was found. Malathion also suppressed the level of testosterone significantly Results of the present study clearly suggest that malathion induce toxic effects on the male reproductive system of rats.

Sex differences in angiotensin II- induced hypertension

Sex differences in the development of hypertension and cardiovascular disease have been described in humans and in animal models. In this paper we will review some of our studies which have as their emphasis the examination of the role of sex differences and sex steroids in modulating the central actions of angiotensin II (ANG II) via interactions with free radicals and nitric oxide, generating pathways within brain circumventricular organs and in central sympathomodulatory systems. Our studies indicate that low-dose infusions of ANG II result in hypertension in wild-type male mice but not in intact wild-type females. Furthermore, we have demonstrated that ANG II-induced hypertension in males is blocked by central infusions of the androgen receptor antagonist, flutamide, and by central infusions of the superoxide dismutase mimetic, tempol. We have also found that, in comparison to females, males show greater levels of intracellular reactive oxygen species in circumventricular organ neurons following long-term ANG II infusions. In female mice, ovariectomy, central blockade of estrogen receptors or total knockout of estrogen a receptors augments the pressor effects of ANG II. Finally, in females but not in males, central blockade of nitric oxide synthase increases the pressor effects of ANG II. Taken together, these results suggest that sex differences and estrogen and testosterone play important roles in the development of ANG II-induced hypertension.

Galanin stimulates hCG induced testicular steroidogenesis in adult but not in immature male rats.

The present study was undertaken to understand the role of galanin on testosterone secretion. Leydig cells from adult (60-80 days old) and immature (21-30 days old) rat testis were incubated with galanin (100 nM), galantide (100 nM) and Human Chorionic Gonadotropin (hCG, 25 I.U.) alone or in combinations and testosterone release was measured. It was observed that in adults, galanin failed to alter the basal testosterone release from the dispersed Leydig cells but potentiated the hCG induced testosterone release significantly. While galantide, prevented this galanin potentiating effect, but it did not alter the hCG alone induced testosterone release. On the other hand, the Leydig cells obtained from immature male rats were sensitive to hCG alone but not to galanin or galantide, both of which failed to alter the hCG induced testosterone release from these cells. Based on these results it can be postulated that galanin's role at the level of the male gonad is age dependent since its potentiating effects on hCG induced testosterone release were visible only in the adult and not in the immature male rats.

Effect of exogenous selenium on the testicular toxicity induced by ethanol in rats.

The effects of supplementation of selenium at a dose of 10 microg/ kg body weight were investigated on ethanol induced testicular toxicity in rats. In the present study, four groups of male albino rats were maintained for 60 days, as follows: (1) Control group (normal diet) (2) Ethanol group (4g/kg body weight) (3) Selenium (10 microg/kg body weight) (4) Ethanol + Selenium (4g/kg body weight + 10 microg/kg body weight). Results revealed that ethanol intake caused drastic changes in the sperm count, sperm motility and sperm morphology. It also reduced the levels of testosterone and fructose. The activities of 3betaHSD, 17betaHSD in the testis and SDH in the seminal plasma were also reduced. Lipid peroxidation was also enhanced as the lipid peroxidation products were increased and the activities of the scavenging enzymes were reduced. But on coadministration of selenium along with alcohol all the biochemical parameters were altered to near normal levels indicating a protective effect of selenium. These results were reinforced by the histopathological studies.

Effect of testosterone on skeletal muscle of young and old male rats

The effects of testosterone on skeletal muscle were assessed in adult male Wistar rats aged 80 days and 1 year. The animals were divided into 4 groups: young testosterone (YT), old testosterone (OT), young control (YC), and old control (OC) groups. The YT and OT groups received 15 applications of testosterone cypionate (5 mg/kg) on alternate days and the controls received injections containing sterile oil alone. After 30 days the animals were sacrificed and the soleus (SOL) and extensor digitorum longus (EDL) muscles were analyzed using mATPase histochemistry. After treatment, YT group gained less body weight than YC group and OT group decreased body weight, differently from the body weight gain observed in the OC group. Testosterone treatment did not show significant changes in both relative muscle weight and muscle fiber composition profile. However, in the YT group we observed an increase in the cross-sectional area of type I fibers in the SOL muscle, and type I and IIAD fibers in the EDL muscle. In the OT group, the cross sectional area of type I was decreased in the EDL muscle. These results reveal that testosterone did not cause a shift in muscle fiber type, but the cross-sectional area had fiber type-specific changes.

Mouse model of male germ cell apoptosis in response to a lack of hormonal stimulation.

As a prerequisite for studies using mutant mice, we established a mouse model for induction of male germ cell apoptosis after deprivation of gonadotropins and intratesticular testosterone (T). We employed a potent long acting gonadotropin-releasing hormone antagonist (GnRH-A), acyline, alone or in combination with an antiandrogen, flutamide for effective induction of germ cell apoptosis in mice. Combined treatment with continuous release of acyline (3 mg/kg BW/day) with flutamide (in the form of sc pellets of 25 mg) resulted in almost the same level of suppression of spermatogenesis, as judged by testis weight and by germ cell apoptotic index, in 2 weeks as that reported for rats after treatment with 1.25 mg/kg BW Nal-Glu GnRH-A for the same time period. Within the study paradigm, the maximum suppression of spermatogenesis occurred after a single sc injection of high (20 mg/kg BW) dose of acyline with flutamide. The combined treatment resulted in complete absence of elongated spermatids. Germ cell counts at stages VII-VIII showed a significant (P < 0.05) reduction in the number of preleptotene (27.1%) and pachytene spermatocytes (81.9%), and round spermatids (96.6%) in acyline + flutamide group in comparison with controls. In fact, treatment with a single high (20 mg/kg BW) dose of acyline combined with flutamide in mice achieved same or greater level of suppression, measured by germ cell counts at stages VII-VIII, in two weeks when compared with those reported after daily treatment with Nal-Glu GnRH-A for 4 weeks in rats. Both plasma and testicular T levels were markedly suppressed after administration of acyline alone either by miniosmotic pump or by a single sc injection. Addition of flutamide to acyline had no discernible effect on plasma or intratesticular T levels when compared with acyline alone. These results demonstrate that optimum suppression of spermatogenesis through increased germ cell death is only possible in mice if total abolition of androgen action is achieved and further emphasize the usefulness of acyline + flutamide treated mice as a suitable model system to study hormonal regulation of testicular germ cell apoptosis.