This study hypothesized that SCFA, acetate impacts positively on hypothalamic pyroptosis and its related abnormalities in experimentally induced PCOS rat model, possibly through NrF2/HIF1-α modulation. Eight-week-old female Wister rats were divided into groups (n = 5), namely control, PCOS, acetate and PCOS + acetate groups. Induction of PCOS was performed by administering 1 mg/kg body weight of letrozole for 21 days. After PCOS confirmation, the animals were treated with 200 mg/kg of acetate for 6 weeks. Rats with PCOS were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles. There was also a significant increase in hypothalamic triglyceride level, triglyceride-glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and caspase-6 as well as plasma LH and triglyceride. A decrease was observed in plasma adiponectin, GnRH, FSH, and hypothalamic GABA with severe inflammasome expression in PCOS rats. These were accompanied by decreased level of NrF2/HIF1-α, and the alterations were reversed when treated with acetate. Collectively, the present results suggest the therapeutic impact of acetate on hypothalamic pyroptosis and its related comorbidity in PCOS, a beneficial effect that is accompanied by modulation of NrF2/HIF1-α.
- MeSH
- adiponektin metabolismus krev MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa * metabolismus MeSH
- faktor 2 související s NF-E2 metabolismus MeSH
- folikuly stimulující hormon krev MeSH
- GABA metabolismus MeSH
- hormon uvolňující gonadotropiny metabolismus MeSH
- hypothalamus * metabolismus účinky léků patologie MeSH
- inzulinová rezistence MeSH
- krysa rodu rattus MeSH
- leptin krev metabolismus MeSH
- letrozol farmakologie MeSH
- luteinizační hormon krev MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar * MeSH
- pyroptóza * účinky léků MeSH
- syndrom polycystických ovarií * chemicky indukované metabolismus farmakoterapie patologie MeSH
- testosteron krev MeSH
- triglyceridy krev metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
This study aimed to investigate the effects of a single bench press (BP) vs. leg press (LP) resistance training sessions on testosterone, cortisol, C-reactive protein (CRP) interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) concentrations, and creatine kinase (CK) activity in strength-trained males. Eleven strength-trained males participated in a cross-over randomized trial, undergoing two experimental sessions each consisting of five sets of the BP or the LP exercise to volitional failure with a load corresponding to 50% of one-repetition maximum. Blood samples were taken at baseline (BA), immediately post (POST), and 1 h after the cessation of exercise (POST-1). A significant increase in IL-6 concentration from BA to POST-1 was observed during the LP condition (p = 0.004; effect size [ES] = 0.64). Additionally, a significant main effect of time was found for increasing testosterone concentrations from BA to POST exercise (p = 0.014; ES = 0.25). A significantly lower cortisol concentration at POST-1 compared to POST (p = 0.001; ES = 1.02) was noted in the BP condition. Furthermore, a significantly lower cortisol concentration was found at POST-1 in the BP compared to the LP condition (p = 0.022; ES = 1.3). A significant increase in CK activity was reported from BA to POST (p = 0.024; ES = 0.69) and POST-1 (p = 0.045; ES = 0.55) during the LP condition, and from BA to POST-1 (p = 0.014; ES = 0.96) during the BP condition. No significant differences were found in the CRP (p = 0.659) and TNF-α concentrations (p = 0.487). These results suggest that the amount of muscle mass engaged during the resistance exercise may influence the changes in IL-6 and cortisol concentrations. Larger muscle groups, as engaged in the LP, more likely lead to elevated concentrations of IL-6 myokine.
- MeSH
- C-reaktivní protein metabolismus MeSH
- dospělí MeSH
- hydrokortison * krev MeSH
- interleukin-6 * krev MeSH
- klinické křížové studie MeSH
- kreatinkinasa krev MeSH
- lidé MeSH
- mladý dospělý MeSH
- odporový trénink * MeSH
- testosteron * krev MeSH
- TNF-alfa * krev MeSH
- zánět krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- MeSH
- hormonální substituční terapie * škodlivé účinky MeSH
- hypogonadismus komplikace MeSH
- kardiovaskulární nemoci chemicky indukované epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty chemicky indukované epidemiologie MeSH
- randomizované kontrolované studie jako téma MeSH
- rizikové faktory kardiovaskulárních chorob * MeSH
- senioři MeSH
- testosteron krev škodlivé účinky MeSH
- urologické nemoci chemicky indukované epidemiologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- komentáře MeSH
Ve sdělení komentujeme studii hodnotící riziko dlouhodobých kardiovaskulárních příhod u mužů s hypogonadismem při substituční terapii testosteronem. Autoři v multicentrické, randomizované, dvojitě zaslepené, placebem kontrolované studii s noninferioritou zařadili muže ve věku 45 až 80 let, kteří měli vysoké riziko kardiovaskulárního onemocnění nebo ho již prodělali. Pacienti udávali symptomy snížené hladiny testosteronu, které byly laboratorně potvrzeny (výsledky hladiny testosteronu v séru na lačno byly < 300 ng/dl (10,4 nmol/L) na základě dvou spolehlivých měření). Randomizace byla provedena 1 : 1 k dennímu užívání gelu s transdermálním podáním obsahujícím 1,62% testosteronu (n = 2 596) nebo odpovídajícího placeba (n = 2 602). Primárním cílovým parametrem kardiovaskulární bezpečnosti byla doba od randomizace do prvního výskytu jakékoli složky závažných nežádoucích srdečních příhod (MACE), která byla hodnocena jako kombinace následujícího: 1. úmrtí z kardiovaskulárních příčin, 2. infarkt myokardu bez fatálního následku, 3. mozková příhoda bez fatálního následku. Primární kardiovaskulární cílový parametr se vyskytl u 182 pacientů (7,0 %) ve skupině léčené testosteronem a u 190 pacientů (7,3 %) ve skupině léčené placebem. Bylo prokázáno, že u mužů s hypogonadismem a již existujícím kardiovaskulárním onemocněním nebo jeho vysokým rizikem nebyla podle analýzy z hlediska MACE substituční terapie testosteronem více riziková než terapie placebem.
This paper comments on a study that evaluates the risk of long-term cardiovascular events in men with hypogonadism undergoing testosterone replacement therapy. In a multicenter, randomized, double-blind, placebo-controlled noninferiority study, the authors included men aged 45 to 80 years who had a high risk of cardiovascular disease or had previously experienced it. Patients reported symptoms of hypogonadism, which were laboratory confirmed (fasting serum testosterone levels were < 300 ng/dl (10.4 nmol/L) based on two reliable measurements). Randomization was conducted in a 1 : 1 ratio for daily use of transdermal 1.62% testosterone gel (n = 2 596) or matching placebo (n = 2 602). The primary cardiovascular endpoint was the time from randomization to the first occurrence of any component of a major adverse cardiovascular event (MACE), which was defined as a combination of the following: (1) cardiovascular death, (2) non-fatal myocardial infarction, (3) non-fatal stroke. Noninferiority required an upper limit of less than 1.5 for the 95% confidence interval of the hazard ratio among patients receiving at least one dose of testosterone or placebo. The primary cardiovascular endpoint occurred in 182 patients (7.0%) in the testosterone-treated group and in 190 patients (7.3%) in the placebo-treated group [HR 0.96; 95% confidence interval, 0.78-1.17; p < 0.001 for noninferiority). In men with hypogonadism and pre-existing or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of MACE, according to the analysis.
- Klíčová slova
- studie TRAVERSE,
- MeSH
- aplikace kožní MeSH
- hormonální substituční terapie * MeSH
- hypogonadismus * farmakoterapie MeSH
- kardiovaskulární nemoci prevence a kontrola MeSH
- lidé středního věku MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- randomizované kontrolované studie jako téma MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- testosteron aplikace a dávkování krev terapeutické užití MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
Minipuberta je definována jako dočasná postnatální aktivace hypotalamo-hypofyzo-gonadální (HPG) osy. Ke spuštění činnosti HPG osy dochází během života celkem třikrát. Poprvé v polovině gestace, kdy se podílí na vývoji a na dozrávání pohlavních žláz. Následuje tzv. minipuberta, která začíná několik dnů po narození a trvá u chlapců 4–6 měsíců a u dívek 2–4 roky. Po „hormonálně klidovém“ dětství přichází klasické pohlavní dospívání s rozvojem sekundárních sexuálních znaků ve druhé dekádě života a je zakončeno kompletní maturací pohlavních žláz umožňující budoucí reprodukci. Existence minipuberty je známa téměř 50 let, ale stále není objasněn její úplný význam. Hladiny pohlavních hormonů dosahují v tomto období téměř k hodnotám dospělých jedinců. U chlapců roste penis, zvětšují se testes, v nichž proliferují zárodečné buňky, u dívek estradiol stimuluje růst prsních žláz a zrání ovariálních folikulů. Fyziologický průběh minipuberty je významný pro budoucí pohlavní vývoj a fertilitu. Toto období je současně několikaměsíčním „oknem příležitosti“ stanovení diagnózy některých vrozených poruch pohlavního vývoje. U chlapců s hypogonadotropním hypogonadismem i s případnou možností včasné léčby. Zvláštní pozornost zasluhují klinické dopady průběhu minipuberty u předčasně narozených dětí a dětí narozených malých na svůj gestační věk. Minipuberta je považována za reálný „předobraz“ budoucího pohlavního vývoje.
Minipuberty is defined as temporary postnatal activation of the hypothalamic-pituitary-gonadal (HPG) axis. The HPG axis is triggered three times during lifetime. The first time in the middle of gestation, when it participates in the development and maturation of the sex glands. This is followed by the so-called minipuberty, which begins a few days after birth and lasts 4-6 months in boys and 2-4 years in girls. After the „hormonally sillent“ childhood comes classical sexual adolescence with the development of secondary sexual signs in the second decade of life and is completed by a complete maturation of the sex glands allowing future reproduction. The existence of mini-puberty has been known for almost 50 years, but its full meaning is still not clarified. Levels of sex hormones reach almost to the values of adult individuals during this period. In boys, the penis grows, testes increase in size, in which germ cells proliferate, in girls, estradiol stimulates the growth of mammary glands and the maturation of ovarian follicles. The physiological course of minipuberty is essential for future sexual development and fertility. At the same time, this period is several months‘ „window of opportunity“ of establishing a diagnosis of some congenital disorders of sexual development. In boys with hypogonadotropic hypogonadism, as well as with the possibility of early treatment. The clinical implications of minipuberty in premature babies and infants born young for their gestational age deserve special attention. Minipuberta is considered a real predicition of future sexual development.
- Klíčová slova
- minipuberta,
- MeSH
- embryonální a fetální vývoj MeSH
- estradiol krev MeSH
- folikuly stimulující hormon krev MeSH
- lidé MeSH
- luteinizační hormon krev MeSH
- novorozenec MeSH
- systém hypotalamus-hypofýza * embryologie MeSH
- testosteron krev MeSH
- vývoj dítěte MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
Clinical studies show that hypogonadism in the aging male is associated with obesity and osteoporosis. Experimental studies are mostly conducted on relatively young adult animals and the induced hypogonadism lasts for a relatively short time. The present study aimed to describe the effect of long-term hypogonadism beginning in puberty on body composition, morphometry, and bone mineral density in aged male rats. Morphometric measurements and dual-energy X-ray absorptiometry were conducted at the age of 30 months on control and gonadectomized males. Long-term hypogonadism did not affect body weight, but led to a higher fat mass (by 26 %), lower lean mass (by 44 %), shorter body length (by 9 %), and anogenital distance (by 26 %), as well as to lower tail circumference (by 15 %) in comparison to control males. Lower bone mineral density (by 13 %) and bone mineral content (by 15 %) were observed in gonadectomized males. Results showing sarcopenic obesity and osteoporosis in this model of long-term hypogonadism might mimic the situation in aging males better than the widely used short-term hypogonadism induced in young animals. The morphometric analysis could potentially be a useful tool to study normal weight obesity without the need for specific equipment.
- MeSH
- adipozita MeSH
- časové faktory MeSH
- hypogonadismus krev patofyziologie MeSH
- kostní denzita MeSH
- modely nemocí na zvířatech MeSH
- obezita krev patofyziologie MeSH
- orchiektomie MeSH
- osteoporóza krev patofyziologie MeSH
- potkani Wistar MeSH
- sarkopenie krev patofyziologie MeSH
- složení těla * MeSH
- testosteron krev MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Extracellular DNA (ecDNA) activates immune cells and is involved in the pathogenesis of diseases associated with inflammation such as sepsis, rheumatoid arthritis or metabolic syndrome. DNA can be cleaved by deoxyribonucleases (DNases), some of which are secreted out of cells. The aim of this experiment was to describe plasma DNase activity in relation to extracellular DNA in adult rats, to analyse potential sex differences and to prove whether they are related to endogenous testosterone. Adult Lewis rats (n=28) of both sexes were included in the experiment. Male rats were gonadectomized or sham-operated and compared to intact female rats. Plasma ecDNA and DNase activity were measured using fluorometry and single radial enzyme diffusion assay, respectively. Concentrations of nuclear ecDNA and mitochondrial ecDNA were determined using real-time PCR. Females had 60% higher plasma DNase activity than males ( p=0.03). Gonadectomy did not affect plasma DNase in males. Neither the concentration of total ecDNA, nor nuclear or mitochondrial DNA in plasma differed between the groups. No significant correlations between DNase and ecDNA were found. From previous studies on mice, it was expected, that male rats will have higher DNase activity. In contrast, our study in rats showed the opposite sex difference. This sex difference seems not to be caused by endogenous testosterone. Interestingly, no sex differences were observed in plasma ecDNA suggesting a complex or missing association between plasma ecDNA and DNase. The observed sex difference in plasma DNase should be taken into account in animal models of ecDNA-associated diseases.
- MeSH
- deoxyribonukleasy krev MeSH
- DNA krev MeSH
- orchiektomie MeSH
- pohlavní dimorfismus * MeSH
- potkani inbrední LEW MeSH
- testosteron krev MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Exposure to chronic stress stimulates the hypothalamic-pituitary-adrenal (HPA) axis and then simultaneously inhibits hypothalamic-pituitary-gonadal axis (HPG) axis activity. The inhibition formed by the HPA axis is the main mechanism of action of stress on reproductive function. HPG axis activity is known to be changed by various factors, including exercise. Exercise has been found to have a number of positive effects on sexual behavior, reproductive hormones, and sperm parameters in studies with animal models for many years. The main aim of this study is to investigate the effects of chronic treadmill exercise on chronically stressed-male rats' sexual behavior, reproductive hormones, and sperm parameters. A total of 40 sexually adult male rats were randomly and equally divided into four groups as control, stress, exercise, and stress+exercise. Animals in the exercise group were subjected to the chronic treadmill exercise (moderate intensity) for 33 days with a periodic increase in speed and duration. Animals in the stress group were exposed to restraint stress for 1 h, 2 h, and 3 h during the first, second and third 15 days respectively. Sexual behavior parameters, hormone measurements, and sperm parameters were evaluated. The main effects of chronic exercise on sexual behavior were centered on a significant increase in the ejaculation frequency (EF) in the stress+exercise group. Also, sperm concentration and motility in the stress group significantly decreased, and then sperm motility was improved by exercise in the stress+exercise group. In sum, our results show that chronic treadmill exercise may improve the adverse effects of chronic stress on sexual behavior and sperm parameters in male rats in terms of some parameters.
- MeSH
- fyzické omezení MeSH
- kondiční příprava zvířat psychologie MeSH
- kortikosteron krev MeSH
- luteinizační hormon krev MeSH
- motilita spermií * MeSH
- počet spermií * MeSH
- potkani Sprague-Dawley MeSH
- psychický stres krev patofyziologie MeSH
- sexuální chování * MeSH
- testosteron krev MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Phthalates are chemicals interfering with the function of testosterone and are suspected to play a role in the emergence of neurodevelopmental diseases. This could be due to interference with brain development for which optimal testosterone levels are essential. We investigated the effect of prenatal and early postnatal exposure to a phthalate mixture on the anogenital distance (AGD), plasma testosterone levels and social behavior in rats. Pregnant rats were exposed to a mixture of diethylhexyl, diisononyl and dibutyl phthalate, each at a dose of 4.5 mg/kg/day, from gestational day 15 to postnatal day 4. A social interaction test was performed to assess sociability in the three ontogenetic stages (weaning, puberty, adulthood). AGD was measured in adulthood to assess changes in prenatal testosterone levels. Plasma testosterone levels were measured in adults by a radioimmunoassay. The total frequency and time of socio-cohesive interactions were decreased in phthalate exposed females in weaning, puberty and adulthood. Phthalate exposed males showed a decrease in the frequency of social interactions in weaning only. Shorter anogenital distance was observed in adult males exposed to phthalates. Decreased testosterone levels were observed in the exposed group in both sexes. Our results suggest that early developmental phthalate exposure may play an important role in the hormonal and behavioral changes associated with several neurodevelopmental diseases.
- MeSH
- dibutylftalát toxicita MeSH
- diethylhexylftalát toxicita MeSH
- krysa rodu rattus MeSH
- kyseliny ftalové toxicita MeSH
- matka - expozice noxám škodlivé účinky MeSH
- novorozená zvířata MeSH
- pohlavní dospělost MeSH
- pohlavní orgány účinky léků patologie MeSH
- potkani Wistar MeSH
- sociální chování * MeSH
- těhotenství MeSH
- testosteron krev MeSH
- zpožděný efekt prenatální expozice chemicky indukované patologie MeSH
- zvířata MeSH
- zvláčňovadla toxicita MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
One of the most common sexual dysfunctional diseases in adult males is premature ejaculation. So far, there is no evidence of how premature ejaculation is associated with psychosocial stress. We tested the relationship between neuroendocrine changes in patients with premature ejaculation and indicators of stress experience as a new psychosomatic hypothesis where psychosocial stress may significantly contribute to the aetiology of premature ejaculation. A total of 55 patients with premature ejaculation were included in the study. The control group consisted of 55 healthy men. The diagnosis of premature ejaculation was confirmed by a sexology examination, a history of patients and the values of the premature ejaculation diagnostic tool questionnaire. Comprehensive biochemical serum analysis was focused on the values of total testosterone, free testosterone, luteinising hormone, thyroid-stimulating hormone, dehydroepiandrosterone sulphate, sex hormone-binding globulin and a premature ejaculation diagnostic tool score with trauma symptom checklist and somatoform dissociation questionnaire. The results show significant Spearman correlations of trauma symptom checklist with the premature ejaculation diagnostic tool score (R = 0.84) and free testosterone (R = 0.62) and somatoform dissociation questionnaire with the premature ejaculation diagnostic tool score (R = 0.53) and free testosterone (R = 0.57). Spearman correlations of trauma symptom checklist with somatoform dissociation questionnaire show significant correlation (R = 0.54).
- MeSH
- disociační poruchy * komplikace MeSH
- dospělí MeSH
- ejakulace MeSH
- lidé MeSH
- luteinizační hormon MeSH
- předčasná ejakulace * diagnóza psychologie MeSH
- průzkumy a dotazníky MeSH
- psychický stres * komplikace MeSH
- testosteron * krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH