RESUMEN
Sex hormones play a pivotal role as endocrine hormones that exert profound effects on the biological characteristics and vascular function of vascular smooth muscle cells (VSMCs). By modulating intracellular signaling pathways, activating nuclear receptors, and regulating gene expression, sex hormones intricately influence the morphology, function, and physiological state of VSMCs, thereby impacting the biological properties of vascular contraction, relaxation, and growth. Increasing evidence suggests that abnormal phenotypic changes in VSMCs contribute to the initiation of vascular diseases, including atherosclerosis. Therefore, understanding the factors governing phenotypic alterations in VSMCs and elucidating the underlying mechanisms can provide crucial insights for refining interventions targeted at vascular diseases. Additionally, the varying levels of different types of sex hormones in the human body, influenced by sex and age, may also affect the phenotypic conversion of VSMCs. This review aims to explore the influence of sex hormones on the phenotypic switching of VSMCs and the development of associated vascular diseases in the human body.
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Hormonas Esteroides Gonadales , Músculo Liso Vascular , Miocitos del Músculo Liso , Humanos , Hormonas Esteroides Gonadales/fisiología , Hormonas Esteroides Gonadales/farmacología , Miocitos del Músculo Liso/fisiología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Animales , Fenotipo , Transducción de Señal/fisiologíaRESUMEN
Elements that interfere with reproductive processes can have profound impacts on population and the equilibrium of ecosystems. Global warming represents the major environmental challenge of the 21st century, as it will affect all forms of life in the coming decades. Another coexisting concern is the persistent pollution by pesticides, particularly the herbicide Atrazine (ATZ), which is responsible for a significant number of contamination incidents in surface waters worldwide. While it is hypothesized that climate changes will significantly enhance the toxic effects of pesticides, the actual impact of these phenomena remain largely unexplored. Here, we conducted a climate-controlled room experiment to assess the interactive effects of the projected 2100 climate scenario and environmentally realistic ATZ exposures on the reproductive function of male zebrafish. The gonadosomatic index significantly decreased in fish kept in the extreme scenario. Cellular alterations across spermatogenesis phases led to synergic decreased sperm production and increased germ cell sloughing and death. ATZ exposure alone or combined with climate change effects, disrupted the transcription levels of key genes involved in steroidogenesis, hormone signaling and spermatogenesis regulation. An additive modulation with decreased 11-KT production and increased E2 levels was also evidenced, intensifying the effects of androgen/estrogen imbalance. Moreover, climate change and ATZ independently induced oxidative stress, upregulation of proapoptotic gene and DNA damage in post-meiotic germ cell, but the negative effects of ATZ were greater at extreme scenario. Ultimately, exposure to simulated climate changes severely impaired fertilization capacity, due to a drastic reduction in sperm motility and/or viability. These findings indicate that the future climate conditions have the potential to considerably enhance the toxicity of ATZ at low concentrations, leading to significant deleterious consequences for fish reproductive function and fertility. These may provide relevant information to supporting healthcare and environmental managers in decision-making related to climate changes and herbicide regulation.
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Atrazina , Cambio Climático , Herbicidas , Testículo , Contaminantes Químicos del Agua , Pez Cebra , Animales , Atrazina/toxicidad , Pez Cebra/fisiología , Masculino , Contaminantes Químicos del Agua/toxicidad , Testículo/efectos de los fármacos , Herbicidas/toxicidad , Espermatogénesis/efectos de los fármacos , Reproducción/efectos de los fármacosRESUMEN
Calcium signaling in vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) is essential for the regulation of vascular tone. However, the changes to intracellular Ca2+ concentrations are often influenced by sex differences. Furthermore, a large body of evidence shows that sex hormone imbalance leads to dysregulation of Ca2+ signaling and this is a key factor in the pathogenesis of cardiovascular diseases. In this review, the effects of estrogens and androgens on vascular calcium-handling proteins are discussed, with emphasis on the associated genomic or nongenomic molecular mechanisms. The experimental models from which data were collected were also considered. The review highlights 1) in female ECs, transient receptor potential vanilloid 4 (TRPV4) and mitochondrial Ca2+ uniporter (MCU) enhance Ca2+-dependent nitric oxide (NO) generation. In males, only transient receptor potential canonical 3 (TRPC3) plays a fundamental role in this effect. 2) Female VSMCs have lower cytosolic Ca2+ levels than males due to differences in the activity and expression of stromal interaction molecule 1 (STIM1), calcium release-activated calcium modulator 1 (Orai1), calcium voltage-gated channel subunit-α1C (CaV1.2), Na+-K+-2Cl- symporter (NKCC1), and the Na+/K+-ATPase. 3) When compared with androgens, the influence of estrogens on Ca2+ homeostasis, vascular tone, and incidence of vascular disease is better documented. 4) Many studies use supraphysiological concentrations of sex hormones, which may limit the physiological relevance of outcomes. 5) Sex-dependent differences in Ca2+ signaling mean both sexes ought to be included in experimental design.
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Señalización del Calcio , Músculo Liso Vascular , Femenino , Masculino , Humanos , Señalización del Calcio/fisiología , Músculo Liso Vascular/metabolismo , Calcio/metabolismo , Andrógenos/metabolismo , Estrógenos/metabolismo , Caracteres Sexuales , Células Endoteliales/metabolismo , Cafeína/farmacología , Miocitos del Músculo Liso/metabolismoRESUMEN
BACKGROUND: Testosterone (T) is an anabolic hormone crucial to the structure and function of skeletal muscle. Testosterone is partially synthesized from cholesterol, but little is known about the relationship of cholesterol intake and serum cholesterol with T levels. AIM: To investigate whether cholesterol intake and serum total cholesterol (TC) levels are associated with serum total testosterone (TT) levels in men. METHODS: A cross-sectional study enrolling 1996 men aged 20 to 80 years from National Health and Nutrition Examination Survey (NHANES) 2013-2014 was carried out. Diet assessment was performed using two 24-h food recalls, and TT levels were measured by liquid chromatography coupled with tandem mass spectrometry. Regression analyses were performed to evaluate whether TT was associated with cholesterol intake and serum TC levels. RESULTS: Neither cholesterol intake nor serum TC levels were associated with TT levels in unadjusted and adjusted analyses (adjustment for energy, total fat and alcohol intake, smoking, age, physical activity, family income, marital status, race, educational level, diabetes, hypertension, and body mass index). CONCLUSION: Dietary cholesterol intake and TC levels are not associated with TT levels in men from the USA.
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Diabetes Mellitus , Testosterona , Masculino , Humanos , Encuestas Nutricionales , Estudios Transversales , ColesterolRESUMEN
Spinal cord injury (SCI) harms patients' health and social and economic well-being. Unfortunately, fully effective therapeutic strategies have yet to be developed to treat this disease, affecting millions worldwide. Apoptosis and autophagy are critical cell death signaling pathways after SCI that should be targeted for early therapeutic interventions to mitigate their adverse effects and promote functional recovery. Tibolone (TIB) is a selective tissue estrogen activity regulator (STEAR) with neuroprotective properties demonstrated in some experimental models. This study aimed to investigate the effect of TIB on apoptotic cell death and autophagy after SCI and verify whether TIB promotes motor function recovery. A moderate contusion SCI was produced at thoracic level 9 (T9) in male Sprague Dawley rats. Subsequently, animals received a daily dose of TIB orally and were sacrificed at 1, 3, 14 or 30 days post-injury. Tissue samples were collected for morphometric and immunofluorescence analysis to identify tissue damage and the percentage of neurons at the injury site. Autophagic (Beclin-1, LC3-I/LC3-II, p62) and apoptotic (Caspase 3) markers were also analyzed via Western blot. Finally, motor function was assessed using the BBB scale. TIB administration significantly increased the amount of preserved tissue (p < 0.05), improved the recovery of motor function (p < 0.001) and modulated the expression of autophagy markers in a time-dependent manner while consistently inhibiting apoptosis (p < 0.05). Therefore, TIB could be a therapeutic alternative for the recovery of motor function after SCI.
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Fármacos Neuroprotectores , Traumatismos de la Médula Espinal , Humanos , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/metabolismo , Apoptosis , Autofagia , Médula Espinal/metabolismo , Recuperación de la Función , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/metabolismoRESUMEN
PURPOSEOF REVIEW: Female sex hormones have systemic effects unrelated to their reproductive function. We describe experiences of different research groups and our own, on aspects related to the importance of female sex hormones on blood pressure (BP) regulation and salt-sensitivity-mediated BP response and salt sensitivity without alterations in BP, as well as renal sodium handling and interactions with the immune system. RECENT FINDINGS: Changes in sodium intake in normotensive premenopausal women cause more BP variations than in men. After menopause, women often develop arterial hypertension (HT) with a profile of sodium sensitivity. Besides, experimental results have shown that in adult rat models resembling the postmenopausal hormonal state induced by ovariectomy, controlling BP is not enough to avoid renal and other tissue infiltration with immune cells, which does not occur when sodium intake is low or normal. Therefore, excess sodium promotes an inflammatory state with the involvement of immune cells. The evidence of activation of adaptive immunity, besides changes in T cell subpopulations, includes changes in sodium transporters and receptors. More studies are needed to evaluate the particular sodium sensitivity of women and its meaning. Changes in lifestyle and sodium intake reduction are the main therapeutic steps. However, to face the actual burden of salt-sensitive HT in postmenopausal women and its associated inflammatory/immune changes, it seems reasonable to work on immune cell activity by considering the peripheral blood mononuclear cell phenotypes of molecules and transport proteins related to sodium handle, both to screen for and treat cell activation.
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Abstract Background: Crocodile farming aims to produce high-quality skins from captive crocodilians. Captivity usually exposes the animals to stressful conditions, resulting in increased serum corticosterone (CORT) levels that correlate negatively with those of sex hormones and reproductive success. Objective: To evaluate serum concentrations of CORT and sex hormones and their relationship in farmed Morelet's crocodiles (Crocodylus moreletii) during the non-breeding (NBS) and breeding (BS) seasons. Methods: The study included 59 adult crocodiles (29 females and 30 males). One blood sample was collected in NBS (n=31) and BS (n=28) from each crocodile to determine serum concentrations of CORT, estradiol (E2), progesterone (P4), and testosterone (T). Crocodiles were kept in mixed-sex groups and were fed once or twice a week throughout the study. Results: In females, CORT was higher in NBS (p<0.05) but had no correlation with E2 or P4 in any season (p>0.05). In males, CORT was similar in NBS and BS (p>0.05) and had no correlation with T (p>0.5). Conclusion: The CORT levels had no effect on sex hormones. This could be explained by low CORT levels resulting from farming conditions were the animals were not expose to severe or chronic stress.
Resumen Antecedentes: La cría de cocodrilos en granja busca producir pieles de alta calidad de cocodrilianos en cautiverio. El cautiverio usualmente expone a los animales a condiciones estresantes, resultando en altas concentraciones séricas de corticosterona (CORT) que se correlacionan negativamente con los niveles de hormonas sexuales y el éxito reproductivo. Objetivo: Evaluar las concentraciones séricas de CORT y de hormonas sexuales y su relación en cocodrilos Moreletii (Crocodylus moreletii) criados en granja, tanto durante la época no reproductiva (NBS) como en la reproductiva (BS). Métodos: El estudio incluyó 59 cocodrilos adultos (29 hembras y 30 machos). Se recolectó una muestra de sangre de cada cocodrilo en NBS (n=31) y BS (n=28) para determinar las concentraciones séricas de CORT, estradiol (E2), progesterona (P4) y testosterona (T). Los cocodrilos permanecieron en grupos mixtos de machos y hembras y fueron alimentados una o dos veces por semana durante el estudio. Resultados: En hembras, CORT fue más alta en NBS (p<0,05), pero no se correlacionó con E2 o P4 en ninguna temporada (p>0,05). En machos, CORT fue similar en NBS y BS (p>0,05) y no tuvo correlación con T (p>0,05). Conclusión: Las concentraciones de CORT no tuvieron efecto sobre las hormonas sexuales, tal vez debido a que la CORT tuvo niveles bajos como resultado de las condiciones de manejo de la granja en las que los animales no se expusieron a estrés severo o crónico.
Resumo Antecedentes: A criação de crocodilos em fazenda procura produzir couros de alta qualidade de crocodilos em cativeiro. O cativeiro geralmente expõe os animais a condições estressantes, resultando em altas concentrações de soro de corticosterona (CORT) que têm correlação negativa com os níveis de hormônios sexuais e o sucesso reprodutivo. Objetivo: Avaliar as concentrações de soro de CORT e hormônios sexuais e sua relação em crocodilos Moreletii (Crocodylus moreletii) criado em fazenda, nas estações de não reprodução (NBS) e reprodução (BS). Métodos: O estudo incluiu 59 crocodilos (29 fêmeas e 30 machos). Uma amostra de sangue foi coletada de cada crocodilo em NBS (n=31) e BS (n=28) para determinar as concentrações de soro de CORT, estradiol (E2), progesterona (P4) e testosterona (T). Ao longo do estudo, os crocodilos permaneceram em grupos mistos de machos e fêmeas e foram alimentados uma ou duas vezes por semana. Resultados: Em fêmeas, CORT foi maior em NBS (p<0,05), mas não teve correlação com E2 ou P4 em qualquer estação (p>0,05). Em machos, CORT foi parecido em NBS e BS (p>0,05) e não teve correlação com T (p>0,05). Conclusão: As concentrações de CORT não tiveram efeito sobre os hormônios sexuais talvez porque o CORT foi baixo como resultado das condições de tratamento em fazenda que não expuseram os animais a estresse severo ou crônico.
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AIMS: This study aimed to evaluate the short- and long-term adverse effects of blood pressure (BP), vascular endothelial function, and estrogen receptor (ERα and ERß) modulation on endothelial function in female Wistar rats treated with topiramate (TPM), an antiepileptic drug, during the peripubertal period. MATERIALS AND METHODS: Female Wistar rats were treated with TPM (41 mg/kg) or water (CTR group) by gavage from postnatal day (PND) 28 to 50 (peripubertal phase). At the end of the treatment, the TPM and CTR rats were divided into two groups and evaluated after 24 h or from PND 85 (adulthood). The rats were evaluated for: thoracic aorta reactivity to phenylephrine (Phenyl), acetylcholine (ACh), and sodium nitroprusside (SNP); aortic ring reactivity after ERα and ERß antagonism; and BP. KEY FINDINGS: It was observed that vascular response to Phenyl, ACh, and SNP was similar between TPM and CTR rats in the short- and long-term evaluations. In addition, the ER antagonism did not interfere with aortic contraction or relaxation in either TPM or CTR. SIGNIFICANCE: Taken together, the results show that TPM treatment during the peripubertal period does not alter aortic endothelial function and its estrogen modulation via classic ER in female Wistar rats, suggesting that TPM treatment in this period is safe for the vascular system.
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Receptor alfa de Estrógeno , Receptor beta de Estrógeno , Ratas , Femenino , Animales , Ratas Wistar , Topiramato/farmacología , Vasoconstricción , Nitroprusiato/farmacología , Fenilefrina/farmacología , Receptores de Estrógenos , Acetilcolina/farmacología , Endotelio VascularRESUMEN
PURPOSE: Most women during their lifetime experience a combination of premenstrual syndrome (PMS) symptoms (eg, menstrual cramps) before and often to the end of menstruation. However, the impact of these symptoms on sport routines (eg, performance, training absence) during phases around menstruation is still unclear. Therefore, we investigated the impact of PMS symptoms on sport routines among nonelite athletes over 3 phases related to menstruation. METHODS: An online questionnaire was developed to recruit nonelite female athletes who participate in summer Olympic sports. Participants were allocated into 2 groups: those who experienced mild to moderate PMS symptoms (no-PMS) and those with severe PMS symptoms (p-PMS). Two hundred thirty-four responses from eumenorrheic women (p-PMS = 78%) were considered valid. An unpaired Student t test was conducted to compare demographic characteristics between groups and chi-square test to evaluate the impact of PMS status on sport routines between groups. RESULTS: A significant (P < .05) proportion of women in the p-PMS group changed their training schedule because of menstrual (55%) and premenstrual (61%) symptoms compared with the no-PMS group. Overall, all participants indicated that training (P = .01) and competitive (P < .01) performance are impacted during menstruation, followed by a greater impact (P < .05) in the p-PMS group before menstruation. CONCLUSION: The presence of PMS symptoms reduces training and competitive performance, primarily during and before menstruation, respectively. Severity of PMS symptoms was significantly associated with alterations in training schedule but not with competitive schedule.
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Síndrome Premenstrual , Deportes , Femenino , Humanos , Síndrome Premenstrual/diagnóstico , Menstruación , Atletas , Encuestas y CuestionariosRESUMEN
Sleep is essential for the maintenance of health and systemic homeostasis. Decreased sleep time and sleep quality have been associated with a wide range of diseases. To evaluate the effects of obstructive sleep apnea (OSA) and total or selective rapid eye movement (REM) sleep deprivation on male reproductive function, we performed a three-arm parallel study with one pre-defined OSA group and a group of healthy volunteers who were then randomised into total or REM sleep deprivation groups. Questionnaires were completed and overnight polysomnography was undertaken, and blood and sperm samples were collected at the Sleep Institute, São Paulo, Brazil. OSA was diagnosed using questionnaires and polysomnography. Male sexual function was assessed through the questionnaires, blood tests, and semen samples. Data showed an association between OSA and lower circulating levels of total and free testosterone and high-density lipoproteins, as well as a lower proportion of healthy sperm cells and decreased sperm concentration, in comparison to volunteers. Volunteers subjected to either total or REM sleep deprivation had increased circulating levels of thyroid-stimulating hormone, insulin, and higher homeostatic model assessment of insulin resistance (HOMA-IR) values. Both sleep-deprived groups also shown decreased cholesterol, and low-density lipoproteins when compared to their baseline levels, but had no alterations in their spermograms. We observed a reduction in total testosterone following total sleep deprivation, but no effect after REM sleep deprivation. OSA was associated with a hormonal imbalance, which is probably linked with impaired reproductive function and associated comorbidities, such as sleep fragmentation/loss and obesity.
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Apnea Obstructiva del Sueño , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Masculino , Privación de Sueño/complicaciones , Brasil , Semen , Apnea Obstructiva del Sueño/diagnóstico , Testosterona , Trastornos del Inicio y del Mantenimiento del Sueño/complicacionesRESUMEN
BACKGROUND: Ionizing radiations (IR) have widespread useful applications in our daily life; however, they have unfavorable effects on reproductive health. Maintaining testicular health following IR exposure is an important requirement for reproductive potential. The current study explored the role of melatonin (MLT) in mitigating IR-induced injury in young adult rat testis. METHODS: Rats were given daily MLT (25 mg/kg) for 3 and 14 days after receiving 4 Gy γ-radiation. RESULTS: Serum MLT levels and other antioxidants, including glutathione content, and the activity of glutathione peroxidase and glutathione reductase in the testis of the irradiated rats were remarkably maintained by MLT administration in irradiated rats. Hence, the hydrogen peroxide level declined with remarkably reduced formation of oxidative stress markers, 4-hydroxynonenal, and 8-Hydroxy-2'-deoxyguanosine in the testis of irradiated animals after MLT administration. The redox status improvement caused a remarkable regression of proapoptotic protein (p53, Cyto-c, and caspase-3) in the testis and improved inflammatory cytokines (CRP and IL-6), and anti-inflammatory cytokine (interleukin IL-10) in serum. This is associated with restoration of disturbed sex hormonal balance, androgen receptor upregulation, and testicular cell proliferation activity in irradiated rats, explaining the improvement of sperm parameters (count, motility, viability, and deformation). Consequently, spermatogenic cell depletion and decreased seminiferous tubule diameter and perimeter were attenuated by MLT treatment post irradiation. Moreover, the testis of irradiated-MLT-treated rats showed well-organized histological architecture and normal sperm morphology. CONCLUSIONS: These results show that radiation-induced testicular injury is mitigated following IR exposure through synergistic interdependence between the antioxidant, anti-inflammatory, anti-apoptotic, and anti-DNA damage actions of MLT.
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Melatonina , Masculino , Ratas , Animales , Melatonina/farmacología , Testículo/metabolismo , Semen/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Radiación Ionizante , Estrés Oxidativo , Antiinflamatorios/farmacologíaRESUMEN
The female hormonal profile is of utmost importance for the assessment of the endocrinological functional status and the diagnosis of diseases. The analysis must delimit their normality intervals based on the manufacturer's cut-off points. Due to not all intervals can be evaluated before use, it is imperative to verify the reference intervals to achieve uniformity in the interpretation of results in the female population. We determine the reference intervals of five female sex hormones [Follicle Stimulating hormone (FSH), Estradiol, Luteinizing Hormone (LH), Prolactin, and progesterone] using electrochemiluminescence in the Cobas e411 (Roche). We included female patients >18 years old, between the 3rd and 15th day of the menstrual cycle (follicular phase) and had no previous medical history or recent medication. For reference intervals analysis, we followed the recommendations of the CLSI C28-A3 guideline. The average concentration for FSH, progesterone, LH, prolactin and estradiol were 11.48 ± 21.10 mIU/ml, 8.19 ± 11.90 ng/ml, 10.98 ± 11.55 ng/ml, 25.05 ± 32.74 ng/mL, and 147.08 ± 473.8 pmol/mL, respectively. Eighty per cent of parameters showed a satisfactory transfer for the manufacturer's reference intervals, except for estradiol, which had 85.5% of transferred values. Our results suggest that 4/5 sex hormones were found within the manufacturer's reference intervals and can be quantified in Peruvian women, ensuring the quality of their results. However, it is necessary to determine the estradiol with other reagents and assays since we show errors in the transfer of intervals.
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Triclosan (TCS) is an antibacterial compound used mainly in personal care products. Its widespread use for decades has made it one of the most widely detected compounds in environmental matrices and in biological fluids. Although it has been shown to be an endocrine disruptor in rats and aquatic species, its safe use by humans is unclear. The aim of the present study was to evaluate the effects of exposure to TCS in female rats. To this end, 14 rats were divided into two groups and fed daily as follows: the control group with sesame oil and the TCS group at a dose of 50 mg/kg/day for 28 days. Any signs of toxicity in the rats were observed daily, and the weight and phase of the estrous cycle were recorded. At the end, the rats were decapitated, the serum and ovaries were collected. The levels of testosterone and progesterone in serum were determined by immunoassay and mass spectrometry. Estradiol (in serum) and kisspeptin-10 (in serum and ovary) were measured only by immunoassays. Trace elements were determined by inductively coupled plasma-mass spectrometry (ICP-MS). The weight gain study of the rats showed a significant decrease by exposure to TCS, while the estrous cycle was not significantly affected compared to the control. The optimized methods based on mass spectrometry showed a significant decrease in the levels of progesterone and testosterone due to exposure to TCS. In addition, elements determined by ICP-MS in rat serum showed significant changes in calcium, lithium and aluminum due to TCS treatment. Finally, the kisspeptin-10 levels did not show a negative effect due to the treatment by TCS. The results suggest that medium-term exposure to TCS did not significantly alter estrous cyclicity but caused alterations in growth, sex hormone levels and some elements in the rat serum.
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Disruptores Endocrinos , Oligoelementos , Triclosán , Aluminio , Animales , Antibacterianos , Calcio , Disruptores Endocrinos/toxicidad , Estradiol , Femenino , Hormonas Esteroides Gonadales , Humanos , Litio , Progesterona , Ratas , Aceite de Sésamo , Testosterona , Triclosán/toxicidadRESUMEN
Early life exposure to sex hormones affects several brain areas involved in regulating locomotor and motivation behaviors. Our group has shown that neonatal exposure to testosterone propionate (TP) or estradiol valerate (EV) affected the brain dopamine (DA) system in adulthood. Here, we studied the long-lasting effects of neonatal exposure to sex hormones on behavioral and neurochemical responses to amphetamine (AMPH) and methylphenidate (MPD). Our results show that AMPH-induced locomotor activity was higher in female than male control rats. The conditioned place preference (CPP) to AMPH was only observed in EV male rats. In EV female rats, AMPH did not increase locomotor activity, but MPD-induced CPP was observed in control, EV and TP female rats. Using in vivo brain microdialysis, we observed that AMPH-induced extracellular DA levels were lower in nucleus accumbens (NAcc) of EV and TP female rats than control rats. In addition, MPD did not increase NAcc extracellular DA levels in EV rats. Using in vivo fast-scan cyclic voltammetry in striatum, MPD-induced DA reuptake was higher in EV than control rats. In summary, our results show that early life exposure to sex hormones modulates mesolimbic and nigrostriatal DA neurons producing opposite neurochemical effects induced by psychostimulant drugs in NAcc or striatum.
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Estimulantes del Sistema Nervioso Central , Metilfenidato , Trastornos Relacionados con Sustancias , Propionato de Testosterona , Anfetamina/farmacología , Animales , Estimulantes del Sistema Nervioso Central/farmacología , Dopamina/farmacología , Estradiol/farmacología , Femenino , Masculino , Metilfenidato/farmacología , Actividad Motora , Núcleo Accumbens , RatasRESUMEN
PURPOSE: Vitamin D (VD) acts on sperm motility, capacitation and survival but its role in steroidogenesis is less clear. Aims: To analyze seasonal variations in sex steroids and VD in a healthy male population. MATERIALS AND METHODS: Twenty-nine healthy males, 34.0±4.8 years were included. Blood collection in winter (W) and summer (S) was performed to measure: 25OHD, total testosterone (TT), free testosterone (FT), estradiol (E2), luteinizing hormone (LH), and sex hormone binding globulin (SHBG). Testosterone/estradiol (T/E2) ratio was calculated. RESULTS: In W, lower levels of 25OHD: 18.8±7.2 ng/mL vs. 38.8±11.9 ng/mL (p<0.0001) and LH: 3.5±1.2 mU/mL vs. 3.9±1.5 mU/mL (p=0.05), and higher levels of TT: 501.9±157.7 ng/dL vs. 405.0±128.0 ng/dL (p=0.0003), FT: 11.8±4.1 ng/dL vs. 10.2±3.7 ng/dL (p=0.017), SHBG: 28.5±10.9 nmol/L vs. 23.6±7.9 nmol/L (p=0.002) and T/E2 ratio: 30.7±19.7 ng/dL/pg/mL vs. 17.3±3.6 ng/dL/pg/mL (p=0.0015) with no variation in E2 levels were observed. A positive correlation between 25OHD and E2 (r=0.28, p=0.04) and negative correlations between 25OHD and TT (r=-0.27, p=0.049), 25OHD and FT (r=-0.32, p=0.01), and 25OHD and T/E2 (r=-0.44, p=0.0008) were found. CONCLUSIONS: In healthy young male population, seasonal variations were observed in 25OHD and LH levels (higher in S) and in TT, FT, SHBG levels, and T/E2 (higher in W). Lower values of TT and FT in S are accompanied by higher levels of LH, which rules out a central mechanism for lowering testosterone. 25OHD negatively correlated with TT, FT, and T/E2 and positively correlated with E2, suggesting a relationship between VD status and changes in gonadal steroids.
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OBJECTIVE: This study aimed at investigating the effect of nanoalumina on sex hormones, and fetuses in pregnant rats. METHODS: In this study, sixty-four pregnant rats were divided into eight groups. The control and the injection-control group received normal food and water, and 0.5 ml of distilled water, respectively. Treatment groups were treated with 25, 50, 100, 250, 500, and 1000µg/ml concentrations of Nanoalumina from the 7th day until the 18th day of pregnancy. On the 18th day, the rats were investigated in terms of their hormone levels. We evaluated the number of healthy and aborted offspring, as well as fetus size. RESULTS: Nanoalumina caused an increase in progesterone hormones at the concentrations of 250, and 500µg/ml, and a significant reduction in estrogen hormone and aborted fetuses at the concentrations of 250 and 500µg/ml (p<0.05). The largest and smallest size of fetuses were observed in 500µg/ml and 1000µg/ml, respectively. The highest number of aborted fetuses was observed in the group treated with the 500µg/ml concentration. There was no aborted fetuses with 25, 50,100, control, and injection-control groups. CONCLUSIONS: Due to nanoalumina toxicity, it must be used with caution.
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Feto , Progesterona , Animales , Femenino , Hormonas , Humanos , Embarazo , Progesterona/farmacología , Ratas , Agua/farmacologíaRESUMEN
BACKGROUND: Ionizing radiations (IR) have widespread useful applications in our daily life; however, they have unfavorable effects on reproductive health. Maintaining testicular health following IR exposure is an important requirement for reproductive potential. The current study explored the role of melatonin (MLT) in mitigating IR-induced injury in young adult rat testis. METHODS: Rats were given daily MLT (25 mg/kg) for 3 and 14 days after receiving 4 Gy γ-radiation. RESULTS: Serum MLT levels and other antioxidants, including glutathione content, and the activity of glutathione peroxidase and glutathione reductase in the testis of the irradiated rats were remarkably maintained by MLT administration in irradiated rats. Hence, the hydrogen peroxide level declined with remarkably reduced formation of oxidative stress markers, 4-hydroxynonenal, and 8-Hydroxy-2'-deoxyguanosine in the testis of irradiated animals after MLT administration. The redox status improvement caused a remarkable regression of proapoptotic protein (p53, Cyto-c, and caspase-3) in the testis and improved inflammatory cytokines (CRP and IL-6), and anti-inflammatory cytokine (interleukin IL-10) in serum. This is associated with restoration of disturbed sex hormonal balance, androgen receptor upregulation, and testicular cell proliferation activity in irradiated rats, explaining the improvement of sperm parameters (count, motility, viability, and deformation). Consequently, spermatogenic cell depletion and decreased seminiferous tubule diameter and perimeter were attenuated by MLT treatment post irradiation. Moreover, the testis of irradiated-MLT-treated rats showed well-organized histological architecture and normal sperm morphology. CONCLUSIONS: These results show that radiation-induced testicular injury is mitigated following IR exposure through synergistic interdependence between the antioxidant, anti-inflammatory, anti-apoptotic, and anti-DNA damage actions of MLT.
Asunto(s)
Animales , Masculino , Ratas , Melatonina/farmacología , Radiación Ionizante , Semen/metabolismo , Testículo/metabolismo , Estrés Oxidativo , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacologíaRESUMEN
Resumo Este artigo analisa a percepção de homens usuários de testosterona acerca dos efeitos adversos no uso do hormônio, a fim de refletir sobre a eficácia e o alcance de ações em saúde voltadas para essa prática. Os dados empíricos foram obtidos a partir de 21 relatos de história de vida de homens que utilizam a testosterona, com ou sem acompanhamento médico, de perfil variado, coletados em 2016 majoritariamente no Rio de Janeiro. A discussão se apoia nos estudos de gênero e de masculinidades para argumentar como os homens interpretam os impactos do uso da testosterona a partir de uma valorização de características masculinas associadas a um ideal normalizador de masculinidade. Os resultados apontam uma percepção generalizada no campo de que o hormônio causa pouco ou nenhum mal, através de um processo de invisibilização ou ressignificação dos efeitos potencialmente negativos. Além disso, há um movimento de deslocamento dos problemas associados ao uso a personagens estereotipadas, num processo de desresponsabilização de si e reafirmação de atributos de um ideal de masculinidade. Com isso, busca-se contribuir para a construção de ações em saúde mais adequadas ao cotidiano dos usuários e, portanto, mais eficazes.
Abstract This article analyzes the perception of male users of testosterone about the adverse effects of the hormone, aiming to challenge the effectiveness and scope of health actions for this practice. Empirical data were obtained in 2016, mostly in Rio de Janeiro, from life history interviews with 21 male users of testosterone, with or without medical monitoring, from different backgrounds. In the light of gender and masculinity studies, it discusses how men interpret the impacts of testosterone use from a social valuation of certain traits associated with a normalizing manhood ideal. Results indicate an invisibilization or re-signification of potentially negative effects of the hormone, culminating in a widespread perception that it causes little or no harm. The problems associated with testosterone use acquire stereotyped characters, through a process of denying self-responsibility and reaffirming attributes of an ideal type of masculinity. This study is expected to contribute to the development of more adequate and thus more effective health actions to users' daily lives.
Asunto(s)
Humanos , Masculino , Hormonas Esteroides Gonadales , Testosterona/efectos adversos , MasculinidadRESUMEN
Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further report that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly, estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV-2 thereby blocking its entry into cells. In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.
Asunto(s)
Estrógenos/química , Estrógenos/metabolismo , SARS-CoV-2/química , SARS-CoV-2/fisiología , Internalización del Virus/efectos de los fármacos , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , Transporte Biológico , COVID-19/metabolismo , Modelos Animales de Enfermedad , Estrógenos/farmacología , Glicosilación/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Ratones Endogámicos C57BL , Modelos Moleculares , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Polisacáridos/química , Polisacáridos/metabolismo , SARS-CoV-2/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Tunicamicina/farmacología , Tratamiento Farmacológico de COVID-19RESUMEN
Andropause results from the natural decrease in testosterone levels that occurs with age. In contrast to menopause, which is a universal, well-characterized process associated with absolute gonadal failure, andropause ensues after gradual decline of both hypothalamic-pituitary-gonadal axis activity, as well as of testicular function, a process which usually develops over a period of many years. Increasing evidence on greater risk of Multiple sclerosis (MS) associated with lower testosterone levels is being reported. Likewise, epidemiological studies have shown a later age of onset of MS in men, relative to women, which could perhaps respond to the decline in protective testosterone levels. In this review, we will discuss the role of androgens in the development and function of the innate and adaptive immune response, as well as in neuroprotective mechanisms relevant to MS. Testosterone effects observed in different animal models and in epidemiological studies in humans will be discussed, as well as their correlation with physical disability and cognitive function levels. Finally, published and ongoing clinical trials exploring the role of androgens, particularly at key stages of sexual maturation, will be reviewed.