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1.
Chemosphere ; 262: 127792, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32805656

RESUMO

Tebuconazole is a triazole fungicide, used in agriculture to treat phytopathogenic fungi, and as a biocide, has been reported to be related to reproductive and developmental toxicity. The purpose of this study was to investigate the effect of tebuconazole exposure on rat fetal Leydig cells and fetal testis during pregnancy. Pregnant Sprague-Dawley rats were randomly divided into 4 groups, daily gavaged with corn oil (as a control), 25, 50, and 100 mg/kg body weight tebuconazole for 10 days (from the 12th day of pregnancy). Tebuconazole increased fetal serum testosterone and progesterone levels at a dose of 100 mg/kg. Exposure to 100 mg/kg tebuconazole significantly caused an increase in the number of fetal Leydig cells per testis without inducing cell aggregation. Tebuconazole up-regulated the expression of Star, Cyp11a1, Hsd17b3, and Fshr and their proteins. Further investigation found that tebuconazole caused increased phosphorylation of AKT1, ERK1/2, and mTOR, the level of BCL2, as well as the decrease of Beclin1, LC3B, and BAX, which may contribute to the fetal Leydig cell autophagy and proliferation. In conclusion, in utero exposure of tebuconazole causes the proliferation of fetal Leydig cells.


Assuntos
Fungicidas Industriais/toxicidade , Células Intersticiais do Testículo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Reprodução/efeitos dos fármacos , Triazóis/toxicidade , Animais , Feminino , Células Intersticiais do Testículo/metabolismo , Masculino , Fosfoproteínas/genética , Fosforilação , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Testículo/efeitos dos fármacos , Testículo/embriologia , Testículo/patologia , Testosterona/sangue , Regulação para Cima
2.
Chemosphere ; 262: 127855, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32799149

RESUMO

Studies have shown that phthalates are capable of affecting the development and functions of male reproductive system. The effect of phthalates on Leydig cell functions is well documented. However, little is known about their potential effects on the functions of stem Leydig cells (SLC). In the present study, we have examined the effects of mono-(2-ethylhexyl) phthalate (MEHP) on SLC functions in vitro by culturing seminiferous tubules and isolated SLCs. The results indicate that MEHP can significantly inhibit the proliferation and differentiation of SLCs in both the organ and cell culture systems. Interestingly, the minimal effective concentration that is able to affect SLC function was lower in the tubule culture system (1 µM) than in the isolated cells (10 µM), suggesting a possible involvement of the niche cells. Also, MEHP appeared to affect both the efficiency of SLCs to form Leydig cells and a selected group of Leydig cell-specific genes, including Lhcgr, Scarb1, Hsd3b1, Cyp17a1, Star, Srd5a1, Akr1c14, Insl3, Hao2 and Pah. Since SLCs are multipotent, we also tested the effect of MEHP on the differentiation of SLCs to adipocytes. Though MEHP by itself can not specify SLCs into adipocyte lineage, it indeed significantly increased the adipogenic activity of SLCs if used with an adipocyte inducing medium by up-regulation of multiple adipogenic-related genes, including Pparg and Cebpa. Overall, the results indicate that MEHP inhibits SLCs differentiating into Leydig lineage while stimulates the differentiating potential of SLCs to adipocytes.


Assuntos
Células Intersticiais do Testículo/efeitos dos fármacos , Ácidos Ftálicos/toxicidade , Adipócitos , Animais , Diferenciação Celular/efeitos dos fármacos , Dietilexilftalato/farmacologia , Masculino , Túbulos Seminíferos/citologia , Esteroide 17-alfa-Hidroxilase , Testosterona/farmacologia
3.
Pol Merkur Lekarski ; 48(287): 323-326, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33130791

RESUMO

Androgenetic alopecia (AGA) is the most common type of hair loss both in male and female patients. As regards its etiopathology, it is postulated that hair follicles grow sensitive to androgens in persons who are genetically predisposed to it. In the pathomechanism of the disease, hair follicles undergo miniaturization. AIM: The aim of the study was to evaluate the levels of selected hormones (sex hormones, adrenal and thyroid hormones), and the results of laboratory tests (iron metabolism) performed in a group of female patients with AGA in order to specify which of those tests should be taken during the diagnostic process in such patients. MATERIALS AND METHODS: Test results and types of therapies have been analyzed for a group of 106 adult female patients (of different age) with female pattern hair loss (FPHL) of different duration. Selected hormone parameters have been analyzed as well as iron metabolism, BMI ( body mass index), and signs of androgenization in the patients' histories (presence of menstrual disorders, hirsutism and acne). Additionally, their insulin levels were measured. RESULTS: The most common hormonal disorders in the study population involved increased concentrations of sex hormone binding globulin (SHBG) in 38.8%, decreased concentration of total testosterone in 25.4%, increased antibody titers against thyroid peroxidase (ATPO) in 17.3%, decreased concentrations of dihydroepiandrostendione (DHEAS) in 15.6%, and increased concentrations of insulin in 12.6%. Increased concentrations of free testosterone were only observed in 6.8 % of the study participants, and increased concentrations of cortisol were revealed in 6.7% of them. 40% of the patients complained about symptoms related to menstrual disorders, hirsutism and acne. Sex hormone concentrations did not correlate with the reported symptoms, and test results in that sub-group were not found to significantly differ from the rest of the patients who did not report signs of hyperandrogenism. CONCLUSIONS: In spite of the fact that nearly half of the patients reported symptoms which may be suggestive of hormonal disorders, no significant abnormalities were revealed in hormone tests.


Assuntos
Alopecia , Hiperandrogenismo , Adulto , Alopecia/diagnóstico , Androgênios , Feminino , Hirsutismo , Humanos , Masculino , Globulina de Ligação a Hormônio Sexual , Testosterona
4.
Eur J Endocrinol ; 183(5): 529-536, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33071222

RESUMO

Objective: Transgender individuals sometimes report a lack of physical change during hormone treatment, such as alterations in muscle tone or fat distribution. Identifying characteristics of this subgroup could be a step toward individualizing hormone therapy in transgender individuals. Therefore, we study the variation of changes in body composition and characteristics associated with a lack of change. Design and methods: Body composition measures were recorded in 323 transmen and 288 transwomen at every visit from the start of hormone therapy to a maximum of 24 months follow-up. Absence of change was defined as transmen with a decrease in lean body mass or transwomen with a decrease in fat percentage. Results: A lack of change at 24 months was observed in 19 of 94 (20.2%) transmen and in 9 of 96 (9.4%) transwomen. The risk of not achieving change in body composition was related to lower testosterone levels and less suppression of LH in transmen (OR: 0.67, 95% CI: 0.48-0.94 per SD increase in testosterone and OR: 1.36, 95% CI: 1.01-1.83 per SD increase in LH). Conclusions: There is a large variation in body composition changes during hormone therapy, with a substantial proportion of individuals with no measurable effects. In transmen, serum testosterone and LH were associated with a lack of change, but serum hormone levels were not associated with body composition changes in transwomen. The results provide a rationale for individualizing hormone therapy in transmen, by considering individual effects rather than solely relying on a standardized dosage of hormone therapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Composição Corporal , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Testosterona/uso terapêutico , Pessoas Transgênero , Adulto , Distribuição da Gordura Corporal , Acetato de Ciproterona/uso terapêutico , Relação Dose-Resposta a Droga , Impedância Elétrica , Estradiol/sangue , Feminino , Humanos , Hormônio Luteinizante/sangue , Masculino , Medicina de Precisão , Procedimentos de Readequação Sexual/métodos , Testosterona/análogos & derivados , Testosterona/sangue , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
6.
Eur J Endocrinol ; 183(6): 561-569, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33055297

RESUMO

Objective: The impact of different combinations of long-term gender-affirming hormone therapy (GAHT) in transwomen (TW) is largely unknown. To assess the effects of 5-year administration of cyproterone acetate (CPA) or leuprolide acetate (Leu) plus transdermal or oral estradiol (E). Design: Cohort study based on prospectively collected data. Fifty TW received 50 mg CPA daily orally (n = 25; CPA+E group) or 3.75 mg Leu i.m. monthly (n = 25; Leu+E group) with 1 or 2 mg E daily for 5 years. Reproductive hormones, biochemical and anthropometric parameters, body composition and bone mineral density (BMD) were assessed. Results: LH, FSH and total testosterone levels were similarly and significantly suppressed in both groups. Prolactin increased only in the CPA+E group (P = 0.002). Fasting insulin resistance and glucose progressively increased in the CPA+E group only (treatment × time effect P = 0.002 and P = 0.043, respectively). Total cholesterol increased more in the Leu+E group than in the CPA+E group and HDL-cholesterol decreased in the CPA+E group (time × treatment interaction effect, P = 0.007). Lumbar and total body BMD increased in both groups after 3 years. No serious adverse events were recorded. Conclusions: Both regimens were effective in suppression of T production. CPA+E worsened the metabolic profile with a slight increase in PRL levels. All subjects presented an increase in BMD regardless of treatment. These preliminary data could have clinical implications in the choice of GAHT, in particular for those TW not requiring gender-affirming surgery.


Assuntos
Acetato de Ciproterona/administração & dosagem , Estradiol/administração & dosagem , Leuprolida/administração & dosagem , Testosterona/sangue , Transexualidade/sangue , Transexualidade/tratamento farmacológico , Adulto , Antagonistas de Androgênios/administração & dosagem , Estudos de Coortes , Esquema de Medicação , Quimioterapia Combinada , Estrogênios/administração & dosagem , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testosterona/antagonistas & inibidores , Pessoas Transgênero
7.
Shanghai Kou Qiang Yi Xue ; 29(4): 380-385, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-33089286

RESUMO

PURPOSE: To investigate the effect of testosterone level on inflammatory bone resorption in periodontitis with mice. METHODS: Forty-eight SD mice were randomly divided into unligated group, sham operation group, castration group, castration + testosterone group, 12 mice in each group. At 6 weeks after ligation, serum testosterone levels were measured, and alveolar bone loss (ABL) and alveolar bone absorption area were compared by hematoxylin - eosin staining and methylene blue staining. The expression of inflammatory cytokine messenger RNA(mRNA) in gingival tissue was measured by real-time fluorescence quantitative PCR. SPSS 20.0 software package was used to analyze the data. RESULTS: Serum testosterone level among four groups was the highest in the unligated group, followed by castration + testosterone group, sham operation group and castration group, with significant difference(P<0.05). The ABL of the castration + testosterone group was significantly larger than that of the unligated group, the sham operation group and the castration group(P<0.05). The ABL of the castration group was significantly smaller than that of the sham operation group (P<0.05). The alveolar bone resorption area of the castration + testosterone group was significantly larger than that of the unligated group, the sham operation group and the castration group(P<0.05). The alveolar bone resorption area of the castration group was significantly smaller than that of the sham operation group (P<0.05). Interleukin-1ß (IL-1ß) mRNA, interleukin-6(IL-6) mRNA and tumor necrosis factor-α(TNF-α) mRNA levels in gingival tissues of sham operation group, castration group and castration + testosterone group were significantly higher than the unligated group. The levels of interleukin-10(IL-10) mRNA in gingival tissues of sham operation group, castration group and castration + testosterone group were significantly lower than those in unligated group(P<0.05). The level of IL-1ß mRNA in gingival tissues among four groups was the the highest in the unligated group, followed by castration + testosterone group, sham operation group and castration group, with significant difference (P<0.05). Serum testosterone levels were positively correlated with ABL, alveolar bone resorption area, and IL-1ß (P<0.05). CONCLUSIONS: Periodontitis with mice have decreased testosterone levels, and long-term testosterone depletion can reduce inflammatory bone resorption in alveolar bone, which may be achieved by reducing the level of IL-1ß, indicating that reduction of the level of testosterone in periodontitis patients may be a new treatment target for alveolar bone resorption.


Assuntos
Perda do Osso Alveolar , Periodontite , Animais , Citocinas , Humanos , Camundongos , Testosterona , Microtomografia por Raio-X
8.
Eur J Endocrinol ; 183(6): R167-R183, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33105105

RESUMO

Overt hypogonadism in men adversely affects body composition and metabolic health, which generally improve upon testosterone (TS) therapy. As obese men often display lower serum TS levels, in particular when they present with the metabolic syndrome (MetS) or type 2 diabetes (T2DM), there have been claims that androgen therapy prevents or reverses obesity and improves metabolic health. This has contributed to the increase in TS prescriptions during the past two decades. In this narrative review, based on findings from larger observational studies and randomized controlled intervention trials, we evaluate whether low TS predicts or predisposes to obesity and its metabolic consequences, and whether obese men with low TS are truly hypogonadal. We further describe the mechanisms underlying the bi-directional relationships of TS levels with obesity and metabolic health, and finally assess the evidence for TS therapy in men with obesity, MetS and/or T2DM, considering efficacy, safety concerns and possible alternative approaches. It is concluded that low serum sex hormone-binding globulin and total TS levels are highly prevalent in obese men, but that only those with low free TS levels and signs or symptoms of hypogonadism should be considered androgen deficient. These alterations are reversible upon weight loss. Whether low TS is a biomarker rather than a true risk factor for metabolic disturbances remains unclear. Considering the limited number of sound TS therapy trials have shown beneficial effects, the modest amplitude of these effects, and unresolved safety issues, one cannot in the present state-of-the-art advocate TS therapy to prevent or reverse obesity-associated metabolic disturbances. Instead, the focus should remain on lifestyle measures and management of obesity-related consequences.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Hipogonadismo/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Testosterona/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Humanos , Hipogonadismo/sangue , Hipogonadismo/complicações , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Obesidade/sangue , Obesidade/complicações , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Resultado do Tratamento
9.
Science ; 370(6513): 208-214, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33033216

RESUMO

Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor gene FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.


Assuntos
Adaptação Fisiológica/genética , Fator 9 de Crescimento de Fibroblastos/genética , Toupeiras/genética , Elementos Reguladores de Transcrição , Diferenciação Sexual/genética , Esteroide 17-alfa-Hidroxilase/genética , Animais , Inversão Cromossômica , Conjuntos de Dados como Assunto , Feminino , Regulação da Expressão Gênica , Genoma , Camundongos , Camundongos Transgênicos , Sequências de Repetição em Tandem , Testosterona/sangue , Testosterona/genética
11.
Hinyokika Kiyo ; 66(8): 259-264, 2020 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-32882122

RESUMO

Five mg tadalafil was administered once-daily to 48 patients for 6 months. Their International Prostatic Symptoms Score (IPSS), Overactive Bladder Symptoms Score (OABSS), Sexual Health Inventory for Men (SHIM), post-voided residual (PVR) volume, free testosterone (FT) level, prostate-specific antigen level, and highly sensitive C-reactive protein (hsCRP) value obtained before and 6 months after the treatment were analyzed. The treatment significantly improved the IPSS, OABSS, SHIM score, and PVR volume (P<0.05), and significantly increased the mean FT level from 6.68 to 7.10 pg/ml ; P<0.05. We observed no significant changes in the hsCRP value and PSA level. However, elevated FT values were noted in 25 (52.1%) patients 6 months after the treatment (FT-increased group). Compared with the non-FT-increased group, the FT-increased group had markedly lower baseline FT value and higher prostatic volume. In both groups, IPSS and OABSS improved considerably. Moreover, the PVR volume, SHIM score, and hsCRP value markedly improved in the FT-increased group (P<0.05). Thus, 5 mg tadalafil administered oncedaily improved IPSS, OABSS, and erectile function, and increased the FT value, in hypogonadal patients with lower urinary tract symptoms. Furthermore, the hsCRP value declined considerably in patients with posttreatment elevated FT level.


Assuntos
Disfunção Erétil , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Proteína C-Reativa , Humanos , Masculino , Inibidores da Fosfodiesterase 5 , Tadalafila , Testosterona , Resultado do Tratamento
12.
Monaldi Arch Chest Dis ; 90(4)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32945643

RESUMO

Novel coronavirus disease (COVID-19) has affected nearly 7 million individuals and claimed more than 0.4 million lives to date. There are several reports of gender differences related to infection and death due to COVID-19. This raises important questions such as "Whether there are differences based on gender in risk and severity of infection or mortality rate?" and "What are the biological explanation and mechanisms underlying these differences?" Emerging evidences have proposed sex-based immunological, genetic, and hormonal differences to explain this ambiguity. Besides biological differences, women have also faced social inequities and economic hardships due to this pandemic. Several recent studies have shown that independent of age males are at higher risk for severity and mortality in COVID-19 patients. Although susceptibility to SARS-CoV-2 was found to be similar across both genders in several disease cohorts, a disproportionate death ratio in men can be partly explained by the higher burden of pre-existing diseases and occupational exposures among men. At immunological point of view, females can engage a more active immune response, which may protect them and counter infectious diseases as compared to men. This attribute of better immune responses towards pathogens is thought to be due to high estrogen levels in females. Here we review the current knowledge about sex differences in susceptibility, the severity of infection and mortality, host immune responses, and the role of sex hormones in COVID-19 disease.


Assuntos
Imunidade Adaptativa/imunologia , Infecções por Coronavirus/imunologia , Estrogênios/imunologia , Imunidade Inata/imunologia , Pneumonia Viral/imunologia , Testosterona/imunologia , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Mortalidade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Índice de Gravidade de Doença , Caracteres Sexuais , Fatores Sexuais
13.
Medicine (Baltimore) ; 99(36): e22085, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899084

RESUMO

RATIONALE: Testicular tumors represent 1% to 1.5% of all tumors in men. Those derived from Leydig cells are rare and account for 1% of testicular tumors. Leydig tumor cells can produce steroid hormones such as estrogen, progesterone and testosterone. The amount and type of hormones secreted by these tumors may produce complicated clinical characteristics in these patients. PATIENT CONCERNS: Here, we report a patient with azoospermia, a testicular Leydig cell tumor (LCT), and elevated plasma testosterone levels. We describe the diagnostic and therapeutic experience of this case, and our follow-up of the patient's clinical indicators and fertility status. DIAGNOSIS: The patient was diagnosed with azoospermia and a testicular LCT. INTERVENTIONS: The patient underwent testicular tumor removal and long-term follow-up. OUTCOMES: After 4 months of follow-up, the patient's semen examination index significantly improved and his wife became naturally pregnant. At 4 months of gestation, the fetus was delivered because of a ruptured amniotic cavity. Twenty-six months after tumor removal, the patient's sex hormone levels had completely returned to normal and spermatogenic function had partially recovered, but there was no natural pregnancy with his partner. CONCLUSION: For LCTs, testis sparing surgery may provide a safe and feasible option to restore spermatogenic function, although longer-term follow-up is required. Drug assistance may be required to maintain spermatogenic function and achieve fertility, and further research is required.


Assuntos
Azoospermia/complicações , Tumor de Células de Leydig/complicações , Neoplasias Testiculares/complicações , Adulto , Humanos , Tumor de Células de Leydig/patologia , Tumor de Células de Leydig/cirurgia , Masculino , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Testosterona/sangue
14.
Medicine (Baltimore) ; 99(33): e21639, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872027

RESUMO

INTRODUCTION: Anabolic steroids are commonly used by athletes, body builders, and young adults to improve muscle strength. Deleterious effects of anabolic steroids on physical health are well-established. Psychiatric aspects are of particular importance and include psychosis, delirium, mania, depression, and aggression. We describe the case of a young gentleman who was managed as a case of androgenic steroid induced delirium. PATIENT CONCERN: A 33-year-old gentleman presented with increased aggression, hostility, and destructive impulses. He was a regular user of testosterone propionate, testosterone cyprionate and trenbolone acetate up to 200 mg daily in injectable form. His mental status examination showed labile effect, flight of ideas and persecutory delusions. Physical examination was positive for atrophic testes. Laboratory results showed a decreased plasma testosterone level of 9.59 nmol/l (10.4-37.4 nmol/l). Sex Hormone Binding Globulin was 23.8 nmol/l (18.3-54.1 nmol/l) and bioavailable testosterone was 5.110 nmol/l (4.36-14.30 nmol/l). DIAGNOSIS: He was diagnosed as a case of anabolic steroids induced delirium. INTERVENTIONS AND OUTCOME: Patient was treated with regular haloperidol and quetiapine after which his sensorium, speech and behavior improved. He was discharged on haloperidol 7.5 mg and quetiapine 700 mg daily. CONCLUSION: The purpose of this case report is to emphasize on the neuropsychiatric effects and management of anabolic steroids manifested by delirium, increased aggression, hostility, and destructive impulses.


Assuntos
Delírio/induzido quimicamente , Congêneres da Testosterona/efeitos adversos , Adulto , Agressão/efeitos dos fármacos , Antipsicóticos/administração & dosagem , Delírio/tratamento farmacológico , Haloperidol/administração & dosagem , Humanos , Masculino , Fumarato de Quetiapina/administração & dosagem , Testosterona/sangue , Congêneres da Testosterona/administração & dosagem
15.
PLoS One ; 15(9): e0239231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32997686

RESUMO

It is controversially discussed whether immune-deficient mice experience severity in the absence of infection. Because a comprehensive analysis of the well-being of immune-deficient mice under specific pathogen free conditions is missing, we used a multi-parametric test analyzing, corticosterone, weight, nest building and facial expression over a period of 9 month to determine the well-being of two immune-deficient mouse lines (recombination activating gene 2- and interferon gamma receptor-deficient mice). We do not find evidence for severity when comparing immune-deficient mice to their heterozygous immune-competent littermates. Our data challenge the assumption that immune-deficiency per se regardless of housing conditions causes severity. Based on our study we propose to use objective non-invasive parameters determined by laboratory animal science for decisions concerning severity of immune-deficient mice.


Assuntos
Corticosterona/genética , Proteínas de Ligação a DNA/genética , Interferon gama/genética , Camundongos SCID/genética , Animais , Linfócitos B/imunologia , Corticosterona/imunologia , Humanos , Infecções/genética , Infecções/imunologia , Rim/metabolismo , Rim/patologia , Camundongos , Camundongos SCID/imunologia , Dor/genética , Dor/patologia , Receptores de Interferon/deficiência , Receptores de Interferon/genética , Transdução de Sinais/genética , Linfócitos T/imunologia , Testosterona/genética
16.
PLoS One ; 15(9): e0238814, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881970

RESUMO

Prostate cancer (PCa) cells become castrate-resistant after initial tumor regression following castration-based lowering of testosterone (T). De-novo intra-tumoral steroid synthesis is a suggested biological mechanism of castration resistant PCa, but the regulators are unknown. Testicular T production is controlled by the luteinizing hormone/choriogonadotropin receptor (LHCGR). To elucidate the influence of LHCGR on PCa development the presence and effects of LHCGR in PCa and whether LHCGR in serum holds prognostic information in PCa patients is investigated. LHCGR expression was investigated by RT-PCR, WB, IHC, qPCR in PCa cell lines and prostatic tissue. Steroid production was measured in media from cell lines with LC-MS/MS and expression of steroidogenic enzymes with qPCR. Serum LHCGR (sLHCGR) was measured with ELISA in PCa patients (N = 157). Presence of LHCGR was established in prostatic tissue and PCa cell lines. Cell proliferation increased by 1.29-fold in LNCaP (P = 0.007) and 1.33-fold in PC-3 cells (P = 0.0007), when stimulated by luteinizing hormone. Choriogonadotropin stimulation decreased proliferation 0.93-fold in DU145 cells (P = 0.05), but none of the treatments altered steroid metabolite secretion. Low sLHCGR concentration was associated with a higher risk of biochemical failure after radical prostatectomy (HR = 3.05, P = 0.06) and castration resistance (HR = 6.92, P = 0.004) compared to high sLHCGR concentration. LHCGR is expressed in PCa and may exert a growth regulatory role in PCa derived cell lines. A potential prognostic role of sLHCGR for determining recurrence risk in PCa patients is found in this pilot study but needs verification in larger cohorts.


Assuntos
Hormônio Luteinizante/metabolismo , Neoplasias da Próstata/fisiopatologia , Receptores do LH/metabolismo , Idoso , Gonadotropina Coriônica/farmacologia , Humanos , Luteinização/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Próstata/patologia , Prostatectomia/efeitos adversos , Testículo/metabolismo , Testosterona/metabolismo , Células Tumorais Cultivadas
17.
Vnitr Lek ; 66(2): 71-76, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32942891

RESUMO

INTRODUCTION: The objective of the study was to examine the relationship between the values of selected parameters of physical function, body composition, body mass index (BMI) and biochemical markers of metabolic health with the total testosterone (TT) levels in adult males. We aimed to analyse the correlation between these values and variations in the TT levels. METHODS: A total of 17 subjects (age = 50.2 ± 8.1 years, TT = 11.4 ± 3.8nmol/l) were included in the study. Subjects were tested on physical function (1RM on leg press, bench-press, handgrip, VO2max), body composition (DXA), biochemical parameters (morning fasting blood samples). RESULTS: TT was inversely correlated with abdominal circumference (AC) (p.


Assuntos
Força da Mão , Testosterona , Adulto , Composição Corporal , Índice de Massa Corporal , Jejum , Humanos , Masculino
18.
Ecotoxicol Environ Saf ; 203: 111053, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888615

RESUMO

Vinclozolin is a common dicarboximide fungicide used to protect crops from diseases. It is also an endocrine disruptor and is thought to be related to abnormalities of the reproductive tract. However, its mechanism of inducing abnormalities of the male reproductive tract is still unclear. The purpose of this study was to study the effect of gestational vinclozolin exposure on the development of rat fetal Leydig cells. Female pregnant Sprague-Dawley rats were exposed to vinclozolin (0, 25, 50, and 100 mg/kg body weight/day) by gavage from gestational day 14-21. Vinclozolin dose-dependently reduced serum testosterone levels at doses of 50 and 100 mg/kg and the anogenital distance at 100 mg/kg. RNA-seq, qPCR, and Western blotting showed that vinclozolin down-regulated the expression of Nr5a1, Sox9, Lhcgr, Cyp11a1, Hsd3b1, Hsd17b3, Amh, Pdgfa, and Dhh and their encoded proteins. Vinclozolin reduced the number of NR2F2-positive stem Leydig cells at a dose of 100 mg/kg and enhanced autophagy in the testes. In conclusion, vinclozolin disrupts reproductive tract development and testis development in male fetal rats via several pathways.


Assuntos
Disruptores Endócrinos/toxicidade , Fungicidas Industriais/toxicidade , Organogênese/efeitos dos fármacos , Oxazóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Testículo/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Testículo/embriologia , Testículo/patologia , Testosterona/sangue
19.
PLoS One ; 15(8): e0237315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866153

RESUMO

The decision to allocate time and energy to find multiple sexual partners or raise children is a fundamental reproductive trade-off. The Strategic Pluralism Hypothesis argues that human reproductive strategies are facultatively calibrated towards either investing in mating or parenting (or a mixture), according to the expression of features dependent on the individual's condition. This study seeks to test predictions derived from this hypothesis in a sample of 242 young men (M ± SD = 22.12 ± 3.08) from Chile's 5th Region (33Ö¯ south latitude). Specifically, two predictions were considered that raise questions about the relationship between traits related to physical and psychological attractiveness (fluctuating facial asymmetry and self-perception of attractiveness) and competitive skills (baseline testosterone and self-perception of fighting ability) with short-term reproductive strategies. Our results indicate that psychological features related to the self-perception of physical attractiveness are related to short-term reproductive strategies. However, no evidence was found that fluctuating facial asymmetry, basal levels of testosterone and self-perception of fighting ability were related to short-term reproductive strategies. These results support the existing evidence of the importance of physical attractiveness in calibrating men's reproductive strategies but cast doubts about the role of fluctuating facial asymmetry. They also suggest that traits related to physical attractiveness, in comparison to competitive capabilities, play a more important role in calibrating men's short-term reproductive strategies.


Assuntos
Beleza , Comportamento de Escolha , Reprodução/fisiologia , Autoimagem , Comportamento Sexual/psicologia , Adolescente , Adulto , Chile , Comportamento Competitivo/fisiologia , Humanos , Parceiros Sexuais/psicologia , Inquéritos e Questionários/estatística & dados numéricos , Testosterona/sangue , Testosterona/fisiologia , Adulto Jovem
20.
PLoS One ; 15(9): e0238051, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915796

RESUMO

The aim of this study was to compare the effects of vibration (Vib versus noVib) during a maximal graded cycling exercise on hormonal response, precisely on cortisol (C) and testosterone (T). Twelve active males (25 ± 5yrs; 181 ± 5cm; 80.7 ± 11.1kg) randomly performed two maximal incremental cycling tests on two separate days and at the same time of the day (09:00). The protocol consisted of incremental steps of 3 min duration performed on a PowerBIKETM that induces vibration cycling. The study was a repeated measures design and participants performed the test with and without vibration. Gas exchange and heart rate (HR) were continuously assessed and blood lactate (Bla) was recorded at the end of each incremental stage. Saliva samples were collected before and immediately after the test, and analysed for (C) and (T). The results show that C and T increased in both cycling conditions; however, the C's magnitude of change was significantly higher by 83% after Vib cycling in comparison to the no Vib (p = 0.014), whereas the T's magnitude of change were not statistically different between trials (p = 0.715). Vibration induced a decrease of the T/C ratio (p = 0.046) but no significant changes were observed following noVib (p = 0.476). As a conclusion, the investigation suggests that adding mechanical vibration to cycling may potentiate a catabolic exercise-induced state, which could have potential clinical implications in rehabilitation and injury treatment. Sport experts should take this message home to carefully plan the recovery process and time during training and competitions.


Assuntos
Ciclismo , Saliva/metabolismo , Vibração , Adolescente , Adulto , Frequência Cardíaca , Humanos , Hidrocortisona/análise , Ácido Láctico/sangue , Masculino , Consumo de Oxigênio , Testosterona/análise , Adulto Jovem
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