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1.
Life Sci ; 237: 116926, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31614148

RESUMO

Sex-related differences in pain and opioids has been the focus of many researches. It is demonstrated that women experience greater clinical pain, lower pain threshold and tolerance, more sensitivity and distress to experimentally induced pain compared to men. Sex differences in response to opioid treatment revealed inconsistent results. However, the etiology of these disparities is not fully elucidated. It is, therefore, conceivable now that this literature merits to be revisited comprehensively. Possible multifaceted factors seem to be associated. These include neuroanatomical, hormonal, neuroimmunological, psychological, social and cultural aspects and comorbidities. This review aims at providing an overview of the substantial literature documenting the sex differences in pain and analgesic response to opioids from animal and human studies within the context of the modulatory effects of the aforementioned factors. A detailed and critical discussion of the cellular and molecular signaling pathways underlying the modulatory actions of gonadal hormones in the sexual dimorphism in pain processing and opioid analgesia is extensively presented. It is indicated that sexual dimorphic activation of certain brain regions contributes to differential pain sensitivity between females and males. Plausible crosstalk between sex hormones and neuroimmunological signaling pertinent to toll-like and purinergic receptors is uncovered as causal cues underlying sexually dimorphic pain and opioid analgesia. Conceivably, a thorough understanding of these factors may aid in sex-related advancement in pain therapeutic management.


Assuntos
Analgésicos Opioides/administração & dosagem , Hormônios Gonadais/metabolismo , Nociceptividade/efeitos dos fármacos , Dor/tratamento farmacológico , Animais , Feminino , Humanos , Masculino , Nociceptividade/fisiologia , Dor/metabolismo , Caracteres Sexuais
2.
J Biochem Mol Toxicol ; 33(11): e22394, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31557376

RESUMO

Triptolide (TP), a major active ingredient of Tripterygium wilfordii, exerts potent immunosuppressive effects in the treatment of rheumatoid arthritis but is not widely used in clinical practice due to its multiorgan toxicity, particularly hepatotoxicity, nephrotoxicity, and reproductive toxicity. An LC-MS/MS approach was employed to explore the endocrine-disrupting effects of TP. The endocrine-disrupting effects of various concentrations (0-100 nM) of TP for 48 hour were firstly investigated using an in vitro model (H295R cell line). It was found that TP did not decrease cell viability. The transcriptional levels of steroidogenic enzymes in H295R cells were assessed by quantificational real-time polymerase chain reaction. The possible adrenal and endocrine effects of oral administration of TP (0, 50, and 500 µg/kg) for 28 days on both normal and collagen-induced arthritis (CIA) rats were also explored. The serum and adrenal tissue hormone levels (corticosterone and progesterone) and adrenal histopathology were analyzed, with the results that TP significantly decreased the level of cortisol in H295R cells and the level of plasma corticosterone in both normal and CIA rats. Histological alterations in adrenal cortex were observed at the dose of 500 µg/kg. Exposure to TP for 48 hour had an obvious inhibitory effect on the messenger RNA transcript levels of HSD3B2, CYP21A2, CYP17A1, and CYP11B1, which is essential for the synthesis of corticosteroids. In a word, TP leads to the disorder of corticosteroid synthesis and secretion, and corticosteroid may be a potential biomarker for the treatment of multiorgan toxicity of TP.


Assuntos
Corticosteroides/metabolismo , Diterpenos/toxicidade , Hormônios Gonadais/metabolismo , Fenantrenos/toxicidade , Extratos Vegetais/toxicidade , Córtex Suprarrenal/patologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida , Compostos de Epóxi/toxicidade , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Progesterona Redutase/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Esteroide Hidroxilases/metabolismo , Espectrometria de Massas em Tandem , Tripterygium/química
3.
J Agric Food Chem ; 67(38): 10553-10562, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31490076

RESUMO

Chlorpyrifos (CPF) is a widely used organophosphorus pesticide and detected frequently in fruits, vegetables, as well as in urine and blood in humans. Studies have suggested that CPF can induce metabolic disruption, such as type-2 diabetes mellitus and changed body weight. The main mechanisms are based on oxidative damage, fatty-acid synthesis, and lipid peroxidation. Studies have also shown that CPF can change reproductive hormone (RH) levels. CPF might result in metabolic disorders through altered RH levels. Here, we review the studies showing that CFP causes metabolic disruption. Then, we present the studies showing that CFP changes RH levels. Finally, we discuss a potential pathway of how CPF elicits metabolic disruption.


Assuntos
Clorpirifos/toxicidade , Hormônios Gonadais/metabolismo , Inseticidas/toxicidade , Doenças Metabólicas/metabolismo , Animais , Humanos , Peroxidação de Lipídeos , Doenças Metabólicas/etiologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-31394254

RESUMO

The present study aimed to evaluate the protective role of Selenium (Se) (0.1 ppm) on the male reproductive system of the catfish Clarias gariepinus exposed to sublethal doses of Mercury (Hg) (0.04 and 0.12 ppm) for 30 days. Indicators of seminal and gonadal hormone disruption (testosterone, estradiol and 11 keto testosterone), antioxidants (total antioxidant capacity (TAO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), oxidative stress biomarkers (lipid peroxidation (LPO), percentage of DNA fragmentation, carbonylated proteins (CP) and nitric oxide (NO)) and histopathological alterations in testicles of Clarias gariepinus were determined. The exposure to Hg resulted in a high accumulation of residues of this metal in testicular tissues. The results showed a significant decrease in sperm count, activity and motility and in all gonadal hormones in Hg exposed groups. Hg exposure also induced a decline in TAO, SOD, CAT and GPx, whereas LPO, DNA fragmentation, CP and NO significantly increased in testicles of C. gariepinus respect to the control group. Although exposure to Se did not reduce the degree of mercury bioconcentration in the testicles, the sperm quality parameters were recovered. Moreover, TAO levels and GPx activity significantly increased after fish exposure to Se, whereas CP levels decreased. LPO, NO, CAT and SOD were also partially normalized when compared with the groups exposed to only Hg. In conclusion, the results showed that Hg, even in the small doses is capable to induce reproductive toxicity in the male catfish. Se exposure partially restored the values of biochemical parameters and sperm quality in Hg-treated fish suggesting protective effects against Hg reproductive toxicity.


Assuntos
Peixes-Gato/metabolismo , Mercúrio/toxicidade , Selênio/farmacologia , Espermatozoides , Testículo , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Hormônios Gonadais/metabolismo , Masculino , Intoxicação por Mercúrio/tratamento farmacológico , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/patologia , Poluentes Químicos da Água/toxicidade
5.
Genes (Basel) ; 10(9)2019 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-31455039

RESUMO

The androgenic gland (AG) is a male-specific endocrine organ that controls the primary and secondary sexual characteristics in male crustaceans. More evidence indicates that the insulin-like androgenic gland hormone gene (IAG) is the key male sexual differentiation factor, particularly the application of RNA interference (RNAi) technology on IAG. In this study, the full-length cDNA of IAG (termed PcIAG) was isolated from the red swamp crayfish, Procambarus clarkii. Tissue distribution analysis showed that in addition to its expression in the AG of male P. clarkii, PcIAG was widely expressed in female tissues and other male tissues. The PcIAG protein was detected in the reproductive and nervous systems of adult male P. clarkii. Additionally, RNAi results showed that the PcIAG expression could be silenced efficiently, and the male sperm maturation and release possibly present a transient adverse interference at lower doses (0.1 µg/g and 1 µg/g) of PcIAG-dsRNA (PcIAG double-stranded RNA). Dramatically, the expression level of PcIAG increased sharply shortly after the injection of higher doses (5 µg/g and 10 µg/g) of PcIAG-dsRNA, which might accelerate the maturation and release of sperm. Moreover, the expression of PcSxl (P. clarkii Sex-lethal) was detected by Quantitative Real-Time PCR (qPCR) after the injection of PcIAG-dsRNA to explore whether the PcIAG gene regulates the PcSxl gene, and we found that the PcIAG did not directly regulate PcSxl in P. clarkii. The study could help accelerate the progress of PcIAG functional research and provide a useful reference for the single-sex selective breeding of P. clarkii.


Assuntos
Astacoidea/genética , Hormônios Gonadais/genética , Diferenciação Sexual , Animais , Astacoidea/crescimento & desenvolvimento , Astacoidea/metabolismo , Glândulas Endócrinas/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Genitália/metabolismo , Hormônios Gonadais/metabolismo , Masculino , Sistema Nervoso/metabolismo , Espermatogênese
6.
Behav Neurosci ; 133(5): 517-526, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31246079

RESUMO

Prior studies suggest that levels of ovarian hormones may affect learning and memory in rats, including studies of fear conditioning and extinction. We previously showed that female rats show reduced retention of extinction compared to males when measuring fear-potentiated startle, but not when measuring freezing behavior. One commonly reported observation in studies of freezing behavior is that rats with increased levels of estradiol during extinction learning show better retention of extinction than rats given extinction training when levels of estradiol are low. Here, we tested the hypothesis that fear extinction retention in a fear-potentiated startle paradigm in females is influenced by levels gonadal hormones, which we had not accounted for in our original report. We used the fear-potentiated startle paradigm to test if extinction learning was affected by estrous phase, ovariectomy, or acute systemic injections of estradiol in ovariectomized rats. We report that neither the expression nor extinction of fear-potentiated startle differed in rats given extinction training in proestrus compared to those in metestrus. Removal of the ovaries had no effect on fear acquisition or extinction learning as assessed by fear-potentiated startle. Finally, systemic injections of estradiol given to ovariectomized rats before extinction training had no effect on the expression of fear or the retention of extinction. Our findings suggest that the effect of female gonadal hormones on fear conditioning and extinction may depend on the measure of fear employed or by the parameters used to study fear learning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Hormônios Gonadais/fisiologia , Animais , Estradiol/farmacologia , Estrogênios/farmacologia , Ciclo Estral/efeitos dos fármacos , Extinção Psicológica/fisiologia , Medo/fisiologia , Feminino , Hormônios Gonadais/metabolismo , Ovariectomia , Ratos , Ratos Sprague-Dawley , Reflexo de Sobressalto/fisiologia
7.
Behav Brain Res ; 363: 13-22, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30703399

RESUMO

The aim of this study was to detect differences in functional outcome after experimental subarachnoid haemorrhage (SAH) in rodents with different hormonal status. For this purpose, the endovascular perforation model was applied to four groups of Sprague-Dawley-Rats: male intact, male neutered, female intact and female neutered animals. Initial impact was measured by ICP, CPP and cerebral blood flow in the first hour after SAH. From day 4-14, the modified hole board test was applied to assess functional and neuro-cognitive outcome. Histological outcome was examined in the motor cortex and hippocampus of each hemisphere. Mortality was highest in the female intact group albeit not statistically significant. Physiologic parameters did not differ significantly between groups either. In the modified hole board test, male intact animals showed a greater impairment of declarative memory than the female intact and neutered groups. However, male intact animals showed greater avoidance behaviour and male animals revealed higher anxiety levels independent of hormonal status. No differences in histological damage of hippocampus and motor cortex between groups could be shown. We therefore speculate that the marginal deficits in cognitive performance that are shown by the male intact group in the modified hole board test are mostly caused by higher anxiety levels and cannot be interpreted as pure cognitive impairment.


Assuntos
Cognição/fisiologia , Hormônios Gonadais/fisiologia , Hemorragia Subaracnóidea/patologia , Animais , Pressão Sanguínea/fisiologia , Encéfalo/patologia , Circulação Cerebrovascular/fisiologia , Feminino , Hormônios Gonadais/metabolismo , Hipocampo/patologia , Pressão Intracraniana/fisiologia , Masculino , Memória , Testes de Estado Mental e Demência , Ratos , Ratos Sprague-Dawley , Fatores Sexuais , Hemorragia Subaracnóidea/metabolismo
8.
Aggress Behav ; 45(2): 193-205, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30597570

RESUMO

Few studies have experimentally manipulated sleep to study its effect on aggressive behavior. The current study examined how reactive aggression was affected by having sleep restricted to 4-hours on a single night, a level of disruption commonly experienced. Both rested and sleep-restricted participants completed the Point Subtraction Aggression Paradigm (PSAP), a laboratory task in which participants seek to earn points, are provoked by a fictitious opponent stealing their points, and may choose to steal points in response. Logistic mixed-effect models were used to investigate the effect of sleep restriction and the role of sex hormones on the odds of choosing to steal. For men, and women in the luteal phase of the menstrual cycle, sleep restriction did not result in significant changes reactive aggression, although the patterns of aggressive behavior appeared less reactive and retaliatory in nature. For women in the follicular phase of the menstrual cycle, sleep restriction was associated with higher levels of reactive aggression. For both men and women in the luteal phase, sleep restriction disrupted an association between hormone change over the task (testosterone and estradiol, respectively) and reactive aggression that was observed in their control participants. In addition, higher testosterone before the PSAP in men was associated with maintaining a high level of stealing over the task. These results indicate a complex dynamic in which sex hormones and sleep interact to predict aggressive behavior in response to provocation.


Assuntos
Agressão/fisiologia , Hormônios Gonadais/metabolismo , Privação do Sono/metabolismo , Adulto , Feminino , Humanos , Relações Interpessoais , Masculino , Privação do Sono/fisiopatologia , Adulto Jovem
9.
Clin Rev Allergy Immunol ; 56(3): 346-361, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28795307

RESUMO

Inflammatory rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) show a striking female predominance ranging from 3:1 in RA up to 9:1 in SLE. The background for those gender bias is not fully understood yet, but seems to be the result of a complex interaction between sex hormones, (epi-)genetics, and possibly even the composition of gut microbiota. Moreover, time of disease onset, the clinical phenotype including co-morbidities as well as the course of the diseases during life differ between genders. The patient's sex therefore plays an emerging role for individual therapy decisions and co-morbidity screening in rheumatologic care. Male lupus patients, for example, tend to show more severe features such as renal involvement, pleurisy, and serositis, when being compared to female patients. Among RA patients, women are more likely to acquire conditions like thyroid dysfunctions, fibromyalgia, and depression than their male counterparts. These examples emphasize the importance of the patient's gender for the clinical routine and the resulting implications for prevention and therapy. The present article is going to review potential causes for the female predominance of rheumatic diseases and will examine the gender's impact on the disease phenotype, symptom severity, co-morbidities, and quality of life. For reasons of scope, the focus will be on RA and SLE as two of the most important rheumatic diseases with a large socioeconomic impact on society due to their incidence as well as mortality.


Assuntos
Artrite Reumatoide/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Qualidade de Vida , Índice de Gravidade de Doença , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/microbiologia , Comorbidade , Epigênese Genética , Feminino , Microbioma Gastrointestinal , Genes Ligados ao Cromossomo X , Hormônios Gonadais/metabolismo , Humanos , Incidência , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/microbiologia , Masculino , Camundongos , Fatores Sexuais
10.
Curr Drug Metab ; 20(1): 9-14, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29380696

RESUMO

BACKGROUND: Kisspeptin and its receptor, GPR54, are regarded as key regulators of and catalysts for male puberty onset, and also fundamental gatekeepers of spermatogenesis in mammals. Consequently, the loss function of kisspeptin or GPR54 leads to a symptom of Hypogonadotropic Hypogonadism (HH) in human and HH accompanied by lower gonadotrophic hormone levels, smaller testes, impaired spermatogenesis and abnormal sexual maturation in mice. Besides its well-recognized functions in hypothalamus before and during puberty, accumulating data strongly support kisspeptin production in testis, and participation in somatic and germ cell development and sperm functions as well. This review aims to summarize recent findings regarding kisspeptin activity in the testes and sperm function. METHODS: We undertook a keyword search of peer-reviewed research literature including data from in vivo and in vitro studies in humans and genetically modified animal models to identify the roles of kisspeptins in male reproduction. RESULTS: A plethora of studies detail the role of kisspeptins and GPR54 in mammalian spermatogenesis in vivo and in vitro. This review identified recent findings regarding the kisspeptin system in male gonads, and regulation of kisspeptin in testicular physiology and male reproductive defects and disorders. CONCLUSION: The findings of this review confirm the importance role of kisspeptins in male fertility. Understanding their biphasic roles in testis may help to consider kisspeptins as potential pharmacological targets for treating human infertility.


Assuntos
Kisspeptinas/metabolismo , Espermatogênese/fisiologia , Animais , Hormônios Gonadais/metabolismo , Humanos , Kisspeptinas/genética , Kisspeptinas/farmacologia , Masculino , Mamíferos , Receptores de Kisspeptina-1/genética , Receptores de Kisspeptina-1/metabolismo , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Testículo/fisiopatologia
11.
Obstet Gynecol Clin North Am ; 45(4): 709-722, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30401552

RESUMO

Sexual function is an important component of quality of life for women. Midlife poses several challenges to optimal sexual function and intimacy for women. In addition to anatomic factors related to estrogen deficiency, such as genitourinary syndrome of menopause, vulvovaginal atrophy, and pelvic organ prolaps, psychosocial factors, including prior sexual trauma, play an important role in sexual function in women. Several treatments have emerged for female sexual dysfunction; long-term studies and head-to-head comparisons are lacking.


Assuntos
Dispareunia/fisiopatologia , Hormônios Gonadais/metabolismo , Menopausa/fisiologia , Disfunções Sexuais Fisiológicas/fisiopatologia , Disfunções Sexuais Psicogênicas/fisiopatologia , Saúde da Mulher , Administração Intravaginal , Dispareunia/psicologia , Terapia de Reposição de Estrogênios , Feminino , Humanos , Lubrificantes , Menopausa/metabolismo , Pessoa de Meia-Idade , Pós-Menopausa/metabolismo , Pós-Menopausa/fisiologia , Qualidade de Vida , Disfunções Sexuais Fisiológicas/psicologia , Disfunções Sexuais Psicogênicas/psicologia
12.
Curr Osteoporos Rep ; 16(6): 674-692, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30328552

RESUMO

PURPOSE OF REVIEW: Patients with chronic kidney disease (CKD) have a greatly increased fracture risk compared with the general population. Gonadal hormones have an important influence on bone mineral density (BMD) and fracture risk, and hormone therapies can significantly improve these outcomes. Gonadal dysfunction is a frequent finding in patients with CKD; yet, little is known about the impact of gonadal hormones in the pathogenesis and treatment of bone health in patients with CKD. This systematic review and meta-analysis aimed to examine the effects of gonadal hormones and hormone therapies on bone outcomes in men and women with CKD. METHODS: EMBASE, MEDLINE, SCOPUS, and clinical trial registries were systematically searched from inception to February 14, 2018 for studies that assessed gonadal hormones or hormone treatments with bone outcomes in patients with CKD stage 3-5D. Two independent reviewers screened the titles and abstracts of search results according to inclusion criteria and assessed study quality and risk of bias using validated assessment tools. RECENT FINDINGS: Thirteen studies met the inclusion criteria. Six moderate-to-high quality observational studies showed inconsistent association between any gonadal hormone and bone outcomes, limited by significant study heterogeneity. Five moderate-high risk of bias interventional studies examined treatment with selective oestrogen receptor modulators in post-menopausal women (four using raloxifene and one bazedoxifene) and demonstrated variable effects on BMD and fracture outcomes. Meta-analysis of raloxifene treatment in post-menopausal women demonstrated improvement in lumbar spine (SMD 3.30; 95% CI 3.21-3.38) and femoral neck (SMD 3.29; 95% CI 3.21-3.36) BMD compared with placebo. Transdermal oestradiol/norethisterone in pre-menopausal women receiving dialysis (n = 1 study), demonstrated BMD improvement over 12 months. Testosterone treatment for 6 months in dialysis-dependant men (n = 1 study) did not improve BMD. There is evidence that raloxifene treatment may be beneficial in improving BMD in post-menopausal women with CKD. There is insufficient evidence for other hormone treatments in men or women. Despite high fracture rates and frequent gonadal dysfunction in patients with CKD, significant evidence gaps exist, and well-designed studies are required to specifically assess the impact of gonadal status in the pathogenesis of CKD-related bone fragility and its treatment.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/fisiologia , Hormônios Gonadais/metabolismo , Osteoporose/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Humanos , Osteoporose/etiologia , Osteoporose/metabolismo , Insuficiência Renal Crônica/metabolismo
13.
Nihon Eiseigaku Zasshi ; 73(3): 313-321, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30270299

RESUMO

In recent years, the birthrate has been continuously declining in Japan. The main causes of the decline are social factors. On the other hand, there is increasing evidence that many environmental chemicals show endocrine disrupting properties. Thus, we hypothesized that exposure to these chemicals would also be a causal for the fertility crisis. In this review, we examined current evidence that focused on environmental chemical exposure in utero and its association with reproductive hormones in children. We have included the findings from a prospective birth cohorts, the Hokkaido Study on Environment and Children's Health Sapporo cohort. According to the literature, environmental chemical levels in utero, such as polychlorinated biphenyl, dioxins, perfluorinated chemical substances, phthalates, and bisphenol A were somewhat associated with the levels of reproductive hormones, such as testosterone, estradiol, progesterone, inhibin B, and insulin-like factor-3 in cord blood, in early childhood and adolescence. The literature also suggests the association between exposure to these chemicals and brain-sexual differentiation or the anogenital distance, which suggests the disruption of androgen shower during the developmental stage in the fetal period. There are still knowledge gaps on whether these hormones at an early stage affect the pubertal development and reproductive functions in later life. In addition, alternative chemicals are produced after banning one type. The health effects of alternative chemicals should be evaluated. Effects of exposure to a mixture of the chemicals should also be examined in future studies. In conclusion, the prevention of environmental chemical hazards in relation to human reproductive function is important. It would be one of the countermeasures to the falling birthrate caused by fertility issues.


Assuntos
Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Hormônios Gonadais/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Exposição Materna/efeitos adversos , Troca Materno-Fetal , Coeficiente de Natalidade/tendências , Criança , Feminino , Desenvolvimento Fetal , Humanos , Infertilidade/etiologia , Masculino , Dinâmica Populacional/estatística & dados numéricos , Dinâmica Populacional/tendências , Gravidez
14.
Am J Physiol Heart Circ Physiol ; 315(6): H1569-H1588, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30216121

RESUMO

Diseases of the cardiovascular system are the leading cause of morbidity and mortality in men and women in developed countries, and cardiovascular disease (CVD) is becoming more prevalent in developing countries. The prevalence of atherosclerotic CVD in men is greater than in women until menopause, when the prevalence of CVD increases in women until it exceeds that of men. Endothelial function is a barometer of vascular health and a predictor of atherosclerosis that may provide insights into sex differences in CVD as well as how and why the CVD risk drastically changes with menopause. Studies of sex differences in endothelial function are conflicting, with some studies showing earlier decrements in endothelial function in men compared with women, whereas others show similar age-related declines between the sexes. Because the increase in CVD risk coincides with menopause, it is generally thought that female hormones, estrogens in particular, are cardioprotective. Moreover, it is often proposed that androgens are detrimental. In truth, the relationships are more complex. This review first addresses female and male sex hormones and their receptors and how these interact with the cardiovascular system, particularly the endothelium, in healthy young women and men. Second, we address sex differences in sex steroid receptor-independent mechanisms controlling endothelial function, focusing on vascular endothelin and the renin-angiotensin systems, in healthy young women and men. Finally, we discuss sex differences in age-associated endothelial dysfunction, focusing on the role of attenuated circulating sex hormones in these effects.


Assuntos
Envelhecimento/fisiologia , Doenças Cardiovasculares/epidemiologia , Endotélio Vascular/metabolismo , Hormônios Gonadais/metabolismo , Animais , Doenças Cardiovasculares/etiologia , Endotélio Vascular/crescimento & desenvolvimento , Endotélio Vascular/fisiopatologia , Humanos , Fatores Sexuais
15.
Environ Pollut ; 243(Pt B): 833-841, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30245445

RESUMO

Glyphosate is the active ingredient of the commercial formulation Roundup®, which is used worldwide. This study aimed to investigate the toxic effects of pure glyphosate or Roundup® on pregnant mice and their fetuses during pregnancy. From gestation days (GDs) 1-19, ICR mice were orally administered distilled water, 0.5% glyphosate solution or 0.5%-glyphosate Roundup® solution. The ovaries and serum were collected at GD19. The results showed decreases in body weight gain and, ovary and liver weight in glyphosate-treated mice. Additionally, histopathological alterations in the ovary including increased atretic follicles, interstitial fibrosis and decreased mature follicles were observed in the groups treated with glyphosate. The serum concentrations of both progesterone and estrogen were markedly altered after glyphosate exposure, and there were also changes in the expression of GnRH, LHR, FSHR, 3ß-HSD and Cyp19a1 genes at the hypothalamic-pituitary-ovarian axis. Furthermore, oxidative stress was observed in the treated mice, increasing the activity of T-AOC, CAT and GSH-Px, as well as the MDA content in both the serum and ovary. With regard to litters, the sex ratio was significantly altered by pure glyphosate. These results show that glyphosate is able to cause several effects on pregnant mice, such as ovarian failure, interference with hormone secretion by affecting the steroidogenesis-related gene expression, and oxidative stress. The sex ratio of litters was also influenced by prenatal exposure to pure glyphosate.


Assuntos
Glicina/análogos & derivados , Hormônios Gonadais/metabolismo , Ovário/efeitos dos fármacos , Razão de Masculinidade , Animais , Feminino , Feto/fisiologia , Glicina/toxicidade , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Gravidez
16.
Mol Metab ; 15: 82-91, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29891438

RESUMO

BACKGROUND: The sex of an individual affects glucose homeostasis and the pathophysiology, incidence, and prevalence of diabetes as well as the response to therapy. SCOPE OF THE REVIEW: This review focuses on clinical and experimental sex differences in islet cell biology and dysfunction during development and in adulthood in human and animal models. We discuss sex differences in ß-cell and α-cell function, heterogeneity, and dysfunction. We cover sex differences in communication between gonads and islets and islet-cell immune interactions. Finally, we discuss sex differences in ß-cell programming by nutrition and other environmental factors during pregnancy. MAJOR CONCLUSIONS: Important sex differences exist in islet cell function and susceptibility to failure. These differences represent sex-related biological factors that can be harnessed for gender-based prevention of and therapy for diabetes.


Assuntos
Diabetes Mellitus/etiologia , Hormônios Gonadais/metabolismo , Ilhotas Pancreáticas/metabolismo , Caracteres Sexuais , Animais , Diabetes Mellitus/epidemiologia , Humanos , Ilhotas Pancreáticas/embriologia , Ilhotas Pancreáticas/imunologia
17.
Mol Metab ; 15: 45-55, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29858147

RESUMO

BACKGROUND: Endogenous sex hormones are important for metabolic health in men and women. Before menopause, women are protected from atherosclerotic cardiovascular disease (ASCVD) relative to men. Women have fewer cardiovascular complications of obesity compared to men with obesity. Endogenous estrogens have been proposed as a mechanism that lessens ASCVD risk, as risk of glucose and lipid abnormalities increases when endogenous estrogens decline with menopause. While baseline risk is higher in males than females, endogenously produced androgens are also protective against fatty liver, diabetes and ASCVD, as risk goes up with androgen deprivation and with the decline in androgens with age. SCOPE OF REVIEW: In this review, we discuss evidence of how endogenous sex hormones and hormone treatment approaches impact fatty acid, triglyceride, and cholesterol metabolism to influence metabolic and cardiovascular risk. We also discuss potential reasons for why treatment strategies with estrogens and androgens in older individuals fail to fully recapitulate the effects of endogenous sex hormones. MAJOR CONCLUSIONS: The pathways that confer ASCVD protection for women are of potential therapeutic relevance. Despite protection relative to men, ASCVD is still the major cause of mortality in women. Additionally, diabetic women have similar ASCVD risk as diabetic men, suggesting that the presence of diabetes may offset the protective cardiovascular effects of being female through unknown mechanisms.


Assuntos
Doenças Cardiovasculares/metabolismo , Hormônios Gonadais/metabolismo , Metabolismo dos Lipídeos , Lipoproteínas/metabolismo , Animais , Doenças Cardiovasculares/epidemiologia , Humanos , Fatores Sexuais
18.
PLoS One ; 13(5): e0196284, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29718954

RESUMO

Castration of dogs is a widespread practise with clear justification in population control and knock-on benefits for animal welfare. Deleterious behavioural consequences of castration are believed to be negligible. Gonadectomy is widely recommended as part of a multi-factorial approach to prevent problems including aggression in dogs. However, the consequences of early castration on health are still being debated. The current study focused on the reported behaviour of 6,235 male dogs castrated before 520 weeks of life for reasons other than behavioural management, and calculated their percentage lifetime exposure to gonadal hormones (PLGH) as a proportion of their age at the time of being reported to the online Canine Behavioral Assessment and Research Questionnaire (C-BARQ). Forty behaviors differed between entire and castrated dogs, of which 25 were associated with PLGH and 14 with age-at-castration (AAC). Only 2 behaviours, indoor urine marking and howling when left alone, were significantly more likely in dogs with longer PLGH. In contrast, longer PLGH was associated with significantly reduced reporting of 26 (mostly unwelcome) behaviours. Of these, 8 related to fearfulness and 7 to aggression. The current data suggest that dogs' tendency to show numerous behaviours can be influenced by the timing of castration. They indicate how dog behaviour matures when gonadal hormones are allowed to have their effect. The differences reported here between undesirable behaviours of castrated and intact dogs were in the range of 5.04% and 12.31%, suggesting that, for some dogs, partial or complete denial of puberty may reduce indoor urine-marking but have many other undesirable consequences. Veterinarians may use these data to discuss unwelcome consequences with owners of male dogs before castration.


Assuntos
Bem-Estar do Animal , Comportamento Animal/fisiologia , Castração/veterinária , Hormônios Gonadais/metabolismo , Maturidade Sexual/fisiologia , Agressão/fisiologia , Animais , Cães , Medo/fisiologia , Masculino , Controle da População/métodos , Inquéritos e Questionários
19.
Aging Cell ; 17(4): e12786, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29806096

RESUMO

Longevity in mammals is influenced by sex, and lifespan extension in response to anti-aging interventions is often sex-specific, although the mechanisms underlying these sexual dimorphisms are largely unknown. Treatment of mice with 17-α estradiol (17aE2) results in sex-specific lifespan extension, with an increase in median survival in males of 19% and no survival effect in females. Given the links between lifespan extension and metabolism, we performed untargeted metabolomics analysis of liver, skeletal muscle and plasma from male and female mice treated with 17aE2 for eight months. We find that 17aE2 generates distinct sex-specific changes in the metabolomic profile of liver and plasma. In males, 17aE2 treatment raised the abundance of several amino acids in the liver, and this was further associated with elevations in metabolites involved in urea cycling, suggesting altered amino acid metabolism. In females, amino acids and urea cycling metabolites were unaffected by 17aE2. 17aE2 also results in male-specific elevations in a second estrogenic steroid-estriol-3-sulfate-suggesting different metabolism of this drug in males and females. To understand the underlying endocrine causes for these sexual dimorphisms, we castrated males and ovariectomized females prior to 17aE2 treatment, and found that virtually all the male-specific metabolite responses to 17aE2 are inhibited or reduced by male castration. These results suggest novel metabolic pathways linked to male-specific lifespan extension and show that the male-specific metabolomic response to 17aE2 depends on the production of testicular hormones in adult life.


Assuntos
Estradiol/farmacologia , Hormônios Gonadais/metabolismo , Longevidade/efeitos dos fármacos , Caracteres Sexuais , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA
20.
Endocrinology ; 159(7): 2596-2613, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29767714

RESUMO

Postnatal development includes dramatic changes in gonadal hormones and the many social behaviors they help regulate, both in rodents and humans. Parental care-seeking is the most salient social interaction in neonates and infants, play and prosocial behaviors are commonly studied in juveniles, and the development of aggression and sexual behavior begins in peripubertal stages but continues through late adolescence into adulthood. Although parental behaviors are shown after reproductive success in adulthood, alloparenting behaviors are actually high in juveniles as well. These behaviors are sensitive to both early-life organizational effects of gonadal hormones and later-life activational regulation. However, changes in circulating gonadal hormones and the display of the previous behaviors over development differ between rats, mice, and humans. These endpoints are of interest to endocrinologist, toxicologists, and neuroscientists because of their relevance to mental health disorders and their vulnerability to effects of endocrine-disrupting chemical exposure. As such, the goal of this mini-review is to succinctly describe and relate the postnatal development of gonadal hormones and social behaviors to each other, over time, and across animal models. Ideally, this will help identify appropriate animal models and age ranges for continued study of both normative development and in contexts of environmental disruption.


Assuntos
Hormônios Gonadais/metabolismo , Comportamento Social , Animais , Feminino , Hormônios Esteroides Gonadais/metabolismo , Humanos , Masculino , Camundongos , Progesterona/metabolismo , Ratos , Comportamento Sexual
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