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1.
Talanta ; 237: 122900, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736715

RESUMO

Developing rapid and reliable method for simultaneous hormones quantitation is of great significant because of important roles of hormones in metabolism. However, current methods are faced with problems of low throughput or complicated operation procedure to remove matrices from serum samples in routine clinical diagnosis. In the present work, a multilayer PS-MS method was developed for rapid and simple detection of hormones. In the strategy, multilayer filter paper acted as the Liquid Chromatography in LC-MS/MS for separation of hormones and biological matrices. Qualitative and quantitative analysis of three hormones, testosterone (T), androsterone (ADT) and androstenedione (4-AD) were realized through MS/MS spectra. The method exhibited linearity in the range of 0.02-2 µg/L and the results of recovery and repeatability were satisfactory for standard samples and spiked serum. The time-cost of a whole detection process was less than 3 min. The established multilayer PS-MS realized rapid, simple and reliable quantitative analysis of various hormones and provided broad prospect for clinical analysis of small molecules in different biological samples. Moreover, it provides a novel MS approach with high through-put and free HPLC, meeting the requirements of point-of-care testing (POCT).


Assuntos
Androstenodiona , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Testosterona
2.
Urologiia ; (5): 5-9, 2021 Nov.
Artigo em Russo | MEDLINE | ID: mdl-34743425

RESUMO

INTRODUCTION: The current epidemiological situation dictates a detailed study of the effect of a new coronavirus infection (SARS-CoV-2) on various anatomical, histological, physiological and biochemical parameters of the human body, which has become an integral part of many medical research, including urology, andrology, endocrinology. OBJECTIVE: To study serum testosterone levels and testicular hemodynamics before and after infection with SARS-CoV-2. MATERIALS AND METHODS: 20 patients were examined, before and after suffering SARS-CoV-2 infection (who fell ill at the beginning of 2020). Average age 37.8 years (min=27, max=50). The level of total testosterone (s) in the blood serum and hemodynamic parameters of the testicles (maximum and minimum blood flow velocity and resistance index) were studied. RESULTS: When studying the level of s 3 months after the transferred SARS-CoV-2, its decrease from the initial value was noted (r=0.47; p=0.35), and after 6 months (r=0.98; p<0.007) there was no recovery of the target level of Ts before infection with SARS-CoV-2. Regarding the hemodynamics of the testicles, there was also a decrease in Vmax and Vmin, and an increase in RI, which indicates a deterioration in the blood flow of the testicles (p<0.001). CONCLUSION: SARS-CoV-2 affects the level of Ts in the blood serum and the parameters of the hemodynamics of the testicles. The extent to which SARS-CoV-2 affects patient performance depends largely on the severity of the disease and to a lesser extent on baseline performance.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Hemodinâmica , Humanos , Masculino , Projetos Piloto , Testículo , Testosterona
3.
Artigo em Inglês | MEDLINE | ID: mdl-34769797

RESUMO

Metabolic and hormonal outcomes of polycystic ovary syndrome (PCOS) have implications on telomere biology and physical activity may prevent telomere erosion. We sought to observe the effects of continuous (CAT) and intermittent (IAT) aerobic training on telomere length, inflammatory biomarkers, and its correlation with metabolic, hormonal, and anthropometric parameters of PCOS. This randomized controlled clinical trial study included 87 PCOS randomly stratified according to body mass index (BMI) in CAT (n = 28), IAT (n = 29) and non-training control group (CG, n = 30). The exercises were carried out on a treadmill, three times per week for 16 weeks. The participants' anthropometric characteristics and biochemical and hormonal concentrations were measured before and after aerobic training or observation period, as the telomere length that was evaluated using quantitative real-time PCR. Four months of aerobic exercises (CAT or IAT) did not alter telomere length and inflammatory biomarkers in PCOS women. Obesity index as BMI and waist circumference (WC), and inflammatory biomarkers negatively affect telomeres. The hyper-andro-genism measured by testosterone levels was reduced after both exercises (CAT, p ≤ 0.001; IAT, p = 0.019). In particular, the CAT reduced WC (p = 0.045), hip circumference (p = 0.032), serum cholesterol (p ≤ 0.001), and low-density lipoprotein (p = 0.030). Whereas, the IAT decreased WC (p = 0.014), waist-to-hip ratio (p = 0.012), free androgen index (FAI) (p = 0.037). WC (p = 0.049) and body fat (p = 0.015) increased in the non-training group while total cholesterol was reduced (p = 0.010). Booth exercises reduced obesity indices and hyperandrogenism on PCOS women without changes in telomere length or inflammatory biomarkers.


Assuntos
Resistência à Insulina , Síndrome do Ovário Policístico , Índice de Massa Corporal , Exercício Físico , Feminino , Humanos , Obesidade , Telômero , Testosterona
4.
Pol Merkur Lekarski ; 49(293): 329-333, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34800017

RESUMO

Data concerning the influence of sex hormones on body composition in women with chronic kidney disease (CKD) is limited. AIM: The aim of our study was to define free testosterone levels and their association with body composition, biochemical markers of nutrition in females with CKD. MATERIALS AND METHODS: 47 women were included into the study. 13 females treated with hemodialysis formed the hemodialysis group (HD), 24 females with CKD stage IV/V (eGFR < 30 ml/min/1,73 m2) formed the predialysis group (PreD), and 10 females without kidney disease formed the control group (C). Lean tissue mass (LTM) and fat mass (Fat) were measured using bioimpedance spectroscopy. Free testosterone levels were assessed using ELISA (IBL International). Statistical analysis was performed using Statistica v 13.1. RESULTS: The median free testosterone (fT) levels were 0.7, 0.6, 0.85 pg/ml respectively for HD, PreD and C group. The median fT did not differ significantly between the groups (p=0.24). The mean LTM was 28.5 ±5.6, 27.3 ±4.9, 30.6 ±4.3 kg, mean Fat mass was 22.7 ±8.5, 31.3 ±9.8, 31.6 ±8.5 kg for the HD, PreD and C groups respectively. Positive correlations were observed between fT and LTM (r=0.306, p=0.035) in the whole study group. A negative correlation was observed between fT and age (r=-0.284) but was on the border of statistical significance (p=0.052). CONCLUSIONS: In women with advanced CKD, median testosterone levels did not differ significantly from those observed in women without kidney failure. Free testosterone levels were associated with the amount of muscle mass in the whole study population.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Composição Corporal , Feminino , Humanos , Diálise Renal , Insuficiência Renal Crônica/terapia , Testosterona
5.
J Med Invest ; 68(3.4): 238-243, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759137

RESUMO

Peripherally derived steroids affect steroid production in the brain via the blood-brain barrier. However, steroid concentrations are lower in the cerebrospinal fluid than those in the blood, indicating restricted influx of steroids because of their metabolization by choroid plexus (CP) epithelial cells. Here, we analyzed the gene expression of steroidogenic enzymes [cholesterol side-chain cleavage enzyme (P450scc), 17α-hydroxylase/C17-C20 lyase (P450c17), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17ß-hydroxysteroid dehydrogenase type 1 (17ß-HSD1), aromatase (Cyp19a1), and 5α-reductase type 1 (5α-R1)]. These genes were expressed to a lesser extent in the CP than in the testis and to a similar extent in the cerebral cortex. However, P450scc levels were higher in the CP than in the cerebral cortex, whereas Cyp19a1 levels showed the opposite trend. We also evaluated the effects of orchiectomy and testosterone on the expression of these genes. P450c17 and 5α-R1 levels were unaffected by orchiectomy, whereas P450scc and 3ß-HSD levels were increased and decreased, respectively. Cyp19a1 expression increased upon testosterone treatment, whereas that of 17ß-HSD decreased upon orchiectomy or administration of testosterone. Immunohistochemistry analysis revealed that 17ß-HSD was expressed in the cytoplasm of CP epithelial cells. These results indicate that CP epithelial cells synthesize and convert the certain types of steroids to contribute to the homeostasis of steroids in the brain. J. Med. Invest. 68 : 238-243, August, 2021.


Assuntos
Enzima de Clivagem da Cadeia Lateral do Colesterol , Plexo Corióideo , Animais , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Plexo Corióideo/metabolismo , Masculino , Ratos , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Esteroides , Testosterona
6.
J Headache Pain ; 22(1): 119, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620097

RESUMO

BACKGROUND: Migraine is a common neurological disease with extremely debilitating, but fully reversible symptoms. Women suffer from migraine more often than men. It was assumed that fluctuation of oestrogen level during menstrual cycle is one of many factors responsible for more frequent migraine attacks. The second-to-fourth digit ratio (2D:4D) is considered as an indicator of prenatal sex steroids. Balance of prenatal androgens (testosterone) and oestrogen has been studied in numerous diseases that are affected by hormones. However, the relationship between migraine and the sex steroids balance in prenatal development is still unexplained. The aim of this paper is to provide an evidence of relationship between prenatal oestrogen and testosterone exposure following 2D:4D digit ratio, and migraine prevalence in adults. METHODS: We examined a group of 151 adults (33 males, 118 females) with migraine and a control group of 111 adults (45 males, 66 females). 2D:4D digit ratio of both hands was measured using sliding Vernier calliper. RESULTS: Significant differences were found in the right hand. Female migraineurs had lower value of 2D:4D ratio than the control group and the right 2D:4D was lower than left 2D:4D (Δ2D:4D), suggesting prenatal testosterone dominance. The opposite relationship was observed in males. Male migraineurs had higher value of 2D:4D ratio and Δ2D:4D was greater than the control group, suggesting prenatal oestrogen dominance. CONCLUSIONS: Our results suggest that depending on sex, different proportion of prenatal sex steroids might be a risk factor of migraine in adults. Women with migraine were presumably exposed in prenatal life to higher testosterone levels relative to oestrogen, while men with migraine were probably exposed in prenatal life to higher levels of oestrogen relative to testosterone.


Assuntos
Transtornos de Enxaqueca , Testosterona , Adulto , Estrogênios , Feminino , Hormônios Esteroides Gonadais , Humanos , Masculino , Transtornos de Enxaqueca/epidemiologia , Fatores de Risco
7.
Artigo em Inglês | MEDLINE | ID: mdl-34639701

RESUMO

In recent years, increasing numbers of women have participated in extremely long races. In adult males, there is a clear association between physiological levels of endogenous sex hormones and physical performance. However, the influence of plasmatic sex hormones and the effects of different types of hormonal contraception (HC) on the modulation of physical performance in adult females remain to be fully clarified. Eighteen female ultra-endurance athletes were recruited to participate in the study. Different variables were studied, including hematological parameters, body mass index, and body composition. Strength measurements were obtained using the squat-jump and hand-grip test. A repeated-measures analysis demonstrated significant differences in hematological values of CK and LDH pre-race as compared to immediately post-race and after 24/48 h. Furthermore, statistical differences were found in squat-jump and hand-grip test results after the ultramarathon. Testosterone, estradiol, and the testosterone/estrogen ratio were significantly correlated with muscle fatigue and were found to be indirect markers of muscle damage. A multivariate analysis demonstrated the protective role of testosterone against muscle damage and severe fatigue. Fluctuations in endogenous testosterone levels were correlated with greater fatigability and muscle damage after the competition. Adjusting the menstrual cycle with HC would not provide any further benefit to the athlete's competitive capacity.


Assuntos
Corrida , Testosterona , Adulto , Atletas , Biomarcadores , Feminino , Humanos , Masculino , Resistência Física
8.
Eur Rev Med Pharmacol Sci ; 25(19): 5889-5903, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34661247

RESUMO

OBJECTIVE: Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19. PATIENTS AND METHODS: We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020. RESULTS: Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality. CONCLUSIONS: Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.


Assuntos
COVID-19/sangue , COVID-19/mortalidade , Estradiol/sangue , Inflamação/sangue , Inflamação/etiologia , Testosterona/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Mortalidade Hospitalar , Hospitalização , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Vitamina D/sangue
9.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638926

RESUMO

Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Inositol/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Testosterona/metabolismo , Células Tecais/efeitos dos fármacos , Diabetes Gestacional/metabolismo , Feminino , Humanos , Inositol/química , Inositol/metabolismo , Estrutura Molecular , Síndrome do Ovário Policístico/metabolismo , Gravidez , Transdução de Sinais/efeitos dos fármacos , Células Tecais/metabolismo
10.
Adv Exp Med Biol ; 1329: 295-323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34664246

RESUMO

Prostate cancer (PCa) is responsible for significant cancer-related morbidity and mortality following local treatment failure in men. The initial stages of PCa are typically managed with a combination of surgical resection and/or androgen deprivation therapy (ADT). Unfortunately, a significant proportion of PCa continues to progress despite being at castrate levels of testosterone (<50 ng/dl), at which point it is coined castration-resistant prostate cancer (CRPC). In recent years, many novel therapeutics and drug combinations have been created for CRPC patients. These include immune checkpoint inhibitors, chemokine receptor antagonists, steroidogenic enzyme inhibition, and novel tyrosine kinase inhibitors as well as combinations of drugs. The selection of the most appropriate therapy depends on several factors like stage of the disease, age of the patient, metastasis, functional status, and response towards previous therapies. Here, we review the current state of the literature regarding treatment modalities, focusing on the treatment recommendations per the American Urological Association (AUA), recent clinical trials, and their limitations. An accurate and reliable overview of the strengths and limitations of PCa therapeutics could also allow personalized therapeutic interventions against PCa.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios/uso terapêutico , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Testosterona , Microambiente Tumoral
12.
Psychiatr Danub ; 33(Suppl 4): 511-517, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34718274

RESUMO

BACKGROUND: Unlike in female population, the effect of testosterone on aggression in men has been investigated countless times so far. A scarce number of studies have examined the effect of testosterone on aggression in women. The results obtained so far are inconsistent for some studies indicated a positive, whilst others showed a negative correlation. Since testosterone turned out to be an important factor related to aggression in men, the aim of our study was to investigate whether this correlation existed in aggressive female patients with schizophrenia. SUBJECTS AND METHODS: The sample consisted of 120 women, aged from 18 to 45 years, diagnosed with schizophrenia by DSM-5 criteria. Those who were breastfeeding or suffered from specific hormonal or other physical disorders were excluded from the study. They were divided into two groups of 60 - those with aggressive behavior and those with nonaggressive behavior. Psychopathology was measured by several tests (Positive and Negative Syndrome Scale - PANSS, Overt Aggression Scale - OAS and PANSS Extended Subscale for Aggression Assessment). Serum testosterone hormone assays were performed. Statistical data analysis was done by parametric statistical tests, Kolmogorov-Smirnov test, Student's t-test and simple linear regression. All data were presented as mean values and corresponding standard deviations (SD). RESULTS: Testosterone levels didn't differ significantly between aggressive and nonaggressive subjects. There were no significant differences between testosterone levels in suicidal aggressive subjects compared to nonsuicidal aggressive respondents (t=0.616; p=0.540). The largest number of subjects in both groups had referent testosterone levels. CONCLUSIONS: Despite expecting a significant effect of testosterone levels on aggression in women with schizophrenia, conducted by previous studies, no correlation has been found. Suicidal behavior surprisingly didn't depend on the subjects' testosterone levels.


Assuntos
Esquizofrenia , Agressão , Feminino , Humanos , Masculino , Ideação Suicida , Testosterona
13.
Nutrients ; 13(10)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34684530

RESUMO

In hypertensive individuals, platelet morphology and function have been discovered to be altered, and this has been linked to the development of vascular disease, including erectile dysfunction (ED). The impact of nutritional supplementation with Cyperus esculentus (tiger nut, TN) and Tetracarpidium conophorum (walnut, WN) on androgen levels, ectonucleotidases, and adenosine deaminase (ADA) activities in platelets from L-NAME (Nω-nitro-L-arginine methyl ester hydrochloride) challenged rats were investigated. We hypothesized that these nuts may show a protective effect on platelets aggregation and possibly enhance the sex hormones, thereby reverting vasoconstriction. Wistar rats (male; 250-300 g; n = 10) were grouped into seven groups as follows: basal diet control group (I); basal diet/L-NAME/Viagra (5 mg/kg/day) as positive control group (II); ED-induced group (basal diet/L-NAME) (III); diet supplemented processed TN (20%)/L-NAME (IV); diet supplemented raw TN (20%)/L-NAME (V); diet supplemented processed WN (20%)/L-NAME (VI); and diet supplemented raw WN (20%)/L-NAME (VII). The rats were given their regular diet for 2 weeks prior to actually receiving L-NAME (40 mg/kg/day) for ten days to induce hypertension. Platelet androgen levels, ectonucleotidases, and ADA were all measured. L-NAME considerably lowers testosterone levels (54.5 ± 2.2; p < 0.05). Supplementing the TN and WN diets revealed improved testosterone levels as compared to the control (306.7 ± 5.7), but luteinizing hormone levels remained unchanged. Compared to control groups, the L-NAME-treated group showed a rise in ATP (127.5%) hydrolysis and ADA (116.7%) activity, and also a decrease in ADP (76%) and AMP (45%) hydrolysis. Both TN and WN supplemented diets resulted in substantial (p < 0.05) reversal effects. Enhanced testosterone levels and modulation of the purinergic system in platelets by TN and WN could be one of the mechanisms by which they aid in vasoconstriction control.


Assuntos
Plaquetas/efeitos dos fármacos , Cyperus , Suplementos Nutricionais , Hipertensão/terapia , Juglans , NG-Nitroarginina Metil Éster/farmacologia , Adenosina Desaminase/efeitos dos fármacos , Difosfato de Adenosina/metabolismo , Monofosfato de Adenosina/metabolismo , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Dieta/métodos , Hidrólise/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Masculino , Proteínas de Membrana/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Purinérgicos/farmacologia , Ratos , Ratos Wistar , Testosterona/sangue , Vasoconstrição/efeitos dos fármacos
14.
Free Radic Biol Med ; 176: 176-188, 2021 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-34610361

RESUMO

Ferroptosis is a newly defined programmed cell death pathway characterized by iron overload and lipid peroxidation. Increasing studies show that autophagy regulates testosterone synthesis and promotes ferroptosis. Testosterone is essential for sexual development and the maintenance of male characteristics. The deficiency of testosterone induced by cadmium (Cd) can severely affect male fertility. However, the underlying mechanism of testosterone reduction after Cd exposure remains blurry. In this study, we found that Cd affected iron homeostasis and elicited ferroptosis, ultimately reducing testosterone production. Mechanically, our findings revealed that Cd-induced ferroptosis depended upon the excessive activation of Heme oxygenase 1 (HMOX1) and the release of free iron from heme. Additionally, Cd exposure promoted autophagosome formation but blocked autophagosome-lysosome fusion, which attenuated the absorption of total cholesterol and triglycerides, further aggravating testosterone synthesis disorder. Collectively, Cd induced ferroptosis by iron homeostasis dysregulation, mediated by excessive activation of HMOX-1. The disruption of autophagy flow contributed to Cd-induced testicular dysfunction and attenuated testosterone synthesis.


Assuntos
Ferroptose , Autofagossomos , Autofagia , Cádmio/toxicidade , Humanos , Lisossomos , Masculino , Testosterona
15.
Aging Male ; 24(1): 139-147, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34647515

RESUMO

Aim: This study aimed to evaluate the effect of physiological testosterone replacement on male aged rats with orchiectomy-induced osteoporosis in advanced stage.Methods: Thirty male rats (Rattus norvegicus albinus, Holtzman lineage) were randomly distributed into 3 groups (n = 10): 1-sham, 2-orchiectomy (OCX), 3-OCX + testosterone replacement (OCX + T). On day 0, a sham or orchiectomy surgery was performed according to the groups. Thirty and sixty days after surgeries, the animals from OCX + T group received testosterone intramuscularly, and the rats in all groups were euthanized on day 77. The femurs were removed for micro-CT scanning and biomechanical test.Results: Orchiectomy resulted in a marked trabecular bone damage (p < 0.05), which was not reversed with testosterone treatment (OCX + T group). The femoral strength was lower in orchiectomized animals (p < 0.05), while the bone strength in OCX + T group was similar to that observed in the sham animals (p > 0.05) and correlated to this parameter the deformation of rupture was smaller in OCX + T group.Conclusion: In conclusion, testosterone depletion induced by orchiectomy established an osteoporotic environment, mainly affecting the trabecular bone. Moreover, even though testosterone treatment did not enhance these variables, the hormonal replacement improved the femoral fracture strength and promoted beneficial effects on the biomechanical parameters compromised by castration in femoral bone.


Assuntos
Orquiectomia , Osteoporose , Animais , Fêmur , Masculino , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Projetos Piloto , Ratos , Testosterona
16.
Oncoimmunology ; 10(1): 1981570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595060

RESUMO

Low response rates to certain tumor types remain a major challenge for immune checkpoint blockade therapy. In this study, we first conducted an integrated biomarker evaluation of bladder cancer patients from confirmatory cohorts (IMvigor210) and found that no significant differences exist between sexes before acceptance of anti-PD-L1 treatment, whereas male patients showed a better response. Thus, we then focused on sex-related changes post anti-PD-L1 treatment and found no obvious impact on the gut microbiota in male mice but a significant decrease in the sex hormone levels. Further, castration dramatically enhanced the antitumor efficacy against murine colon adenocarcinoma in male mice. Moreover, a narrow-spectrum antibiotic, colistin was innovatively used for deregulation of testosterone levels to enhance the immunotherapy efficiency in male mice. These findings indicate that the impact on the sex hormone levels in males may contribute to the sexual dimorphism in response and provide a promising way to enhance immunotherapy efficiency.


Assuntos
Imunoterapia , Neoplasias da Bexiga Urinária , Animais , Humanos , Fatores Imunológicos , Masculino , Camundongos , Testosterona , Neoplasias da Bexiga Urinária/tratamento farmacológico
17.
Med Clin North Am ; 105(6): 1099-1116, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34688417

RESUMO

The approach to hyperandrogenism in women varies depending on the woman's age and severity of symptoms. Once tumorous hyperandrogenism is excluded, the most common cause is PCOS. Hirsutism is the most common presenting symptom. The woman's concern about her symptoms plays an important role in the management of disease. Although measurement of testosterone is useful in identifying an underlying cause, care must be taken when interpreting the less accurate assays that are available commercially. Surgical resection is curative in tumorous etiologies, whereas medical management is the mainstay for non-tumorous causes.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Hiperandrogenismo/tratamento farmacológico , Hiperandrogenismo/fisiopatologia , Fatores Etários , Grupos de Populações Continentais , Feminino , Humanos , Hiperandrogenismo/diagnóstico , Hiperandrogenismo/etiologia , Síndrome do Ovário Policístico/complicações , Testosterona/sangue , Saúde da Mulher
18.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638962

RESUMO

Gaining detailed knowledge about sex-related immunoregulation remains a crucial prerequisite for the development of adequate disease models and therapeutic strategies enabling personalized medicine. Here, the key parameter of the production of cytokines mediating disease resolution was investigated. Among these cytokines, STAT3-activating interleukin (IL)-22 is principally associated with recovery from tissue injury. By investigating paradigmatic acetaminophen-induced liver injury, we demonstrated that IL-22 expression is enhanced in female mice. Increased female IL-22 was confirmed at a cellular level using murine splenocytes stimulated by lipopolysaccharide or αCD3/CD28 to model innate or adaptive immunoactivation. Interestingly, testosterone or dihydrotestosterone reduced IL-22 production by female but not by male splenocytes. Mechanistic studies on PMA/PHA-stimulated T-cell-lymphoma EL-4 cells verified the capability of testosterone/dihydrotestosterone to reduce IL-22 production. Moreover, we demonstrated by chromatin immunoprecipitation that testosterone impairs binding of the aryl hydrocarbon receptor to xenobiotic responsive elements within the murine IL-22 promoter. Overall, female mice undergoing acute liver injury and cultured female splenocytes upon inflammatory activation display increased IL-22. This observation is likely related to the immunosuppressive effects of androgens in males. The data presented concur with more pronounced immunological alertness demonstrable in females, which may relate to the sex-specific course of some immunological disorders.


Assuntos
Acetaminofen/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Expressão Gênica/efeitos dos fármacos , Interleucinas/genética , Interleucinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acetaminofen/sangue , Imunidade Adaptativa/efeitos dos fármacos , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular Tumoral , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/genética , Di-Hidrotestosterona/farmacologia , Modelos Animais de Doenças , Feminino , Imunidade Inata/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/imunologia , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Hidrocarboneto Arílico/metabolismo , Fatores Sexuais , Baço/citologia , Baço/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Testosterona/farmacologia
19.
Curr Opin Endocrinol Diabetes Obes ; 28(6): 604-614, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34709215

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to examine the recent evidence regarding the effects of exogenous androgens on the brain. Understanding these effects is of high importance, as the consequences of androgens on the reproductive and endocrine system are well documented, while fewer studies have focused on the neural and cerebral consequences of androgen use. RECENT FINDINGS: Supraphysiological doses of androgens have been shown to contribute to neurodegeneration, decreased brain-derived neurotrophic factor, increased inflammation and decreased neuronal density in animal studies, which may correspond to changes in mood, cognition and aggression. Findings from human studies suggest that similar behavioural and cognitive deficits may occur as a result of prolonged use of androgens. Additional evidence suggests that androgen use, particularly in high doses, may contribute to brain ageing and cerebrovascular problems. SUMMARY: Findings from recent human and animal studies indicate that androgen use likely contributes to brain alterations, which may cause the frequently observed deficits in cognitive and emotional functioning. Although exogenous testosterone in appropriate doses for therapeutic purposes likely have some neurobiological benefits for certain populations, supraphysiological doses may cause multiple mental and physical health problems, indicating a need for additional large-scale studies in humans.


Assuntos
Androgênios , Testosterona , Envelhecimento , Androgênios/efeitos adversos , Animais , Encéfalo , Cognição , Humanos
20.
Endocrine ; 74(3): 498-507, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34599696

RESUMO

PURPOSE: Members of the AP-1 family of transcription factors are immediate early genes being modulated by different extracellular signals. The aim of this review is to highlight the important roles of AP-1 members in transcriptional regulation of genes important for testicular Leydig cell function and male testosterone production. METHODS: A search of the relevant literature was performed in Google Scholar and NCBI Pubmed for AP-1 members and Leydig cells. Additional information was accessed from references of relevant articles. Only primary data from original peer-reviewed articles was considered for this review. RESULTS: Different signaling pathways important for Leydig cells' functions are involved in the regulation of the activity of AP-1 members. These transcription factors participate in the regulation of genes related to different biological processes important for Leydig cells. CONCLUSIONS: We conclude that members of the AP-1 family of transcription factors play critical roles in the regulation of Leydig cell proliferation, steroidogenesis, and cell-to-cell communication.


Assuntos
Células Intersticiais do Testículo , Fator de Transcrição AP-1 , Expressão Gênica , Humanos , Masculino , Testículo , Testosterona , Fator de Transcrição AP-1/genética
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