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1.
Int J Surg ; 81: 47-54, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32738546

RESUMO

Globally, a staggering 310 million major surgeries are performed each year; around 40 to 50 million in USA and 20 million in Europe. It is estimated that 1-4% of these patients will die, up to 15% will have serious postoperative morbidity, and 5-15% will be readmitted within 30 days. An annual global mortality of around 8 million patients places major surgery comparable with the leading causes of death from cardiovascular disease and stroke, cancer and injury. If surgical complications were classified as a pandemic, like HIV/AIDS or coronavirus (COVID-19), developed countries would work together and devise an immediate action plan and allocate resources to address it. Seeking to reduce preventable deaths and post-surgical complications would save billions of dollars in healthcare costs. Part of the global problem resides in differences in institutional practice patterns in high- and low-income countries, and part from a lack of effective perioperative drug therapies to protect the patient from surgical stress. We briefly review the history of surgical stress and provide a path forward from a systems-based approach. Key to progress is recognizing that the anesthetized brain is still physiologically 'awake' and responsive to the sterile stressors of surgery. New intravenous drug therapies are urgently required after anesthesia and before the first incision to prevent the brain from switching to sympathetic overdrive and activating secondary injury progression such as hyperinflammation, coagulopathy, immune activation and metabolic dysfunction. A systems-based approach targeting central nervous system-mitochondrial coupling may help drive research to improve outcomes following major surgery in civilian and military medicine.


Assuntos
Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Operatórios/mortalidade , Saúde Global , Glicocálix/fisiologia , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Mitocôndrias/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Complicações Pós-Operatórias/prevenção & controle , Estresse Fisiológico , Procedimentos Cirúrgicos Operatórios/efeitos adversos
2.
Endocr Relat Cancer ; 27(9): R281-R292, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32508311

RESUMO

The current pandemic (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health challenge with active development of antiviral drugs and vaccines seeking to reduce its significant disease burden. Early reports have confirmed that transmembrane serine protease 2 (TMPRSS2) and angiotensin converting enzyme 2 (ACE2) are critical targets of SARS-CoV-2 that facilitate viral entry into host cells. TMPRSS2 and ACE2 are expressed in multiple human tissues beyond the lung including the testes where predisposition to SARS-CoV-2 infection may exist. TMPRSS2 is an androgen-responsive gene and its fusion represents one of the most frequent alterations in prostate cancer. Androgen suppression by androgen deprivation therapy and androgen receptor signaling inhibitors form the foundation of prostate cancer treatment. In this review, we highlight the growing evidence in support of androgen regulation of TMPRSS2 and ACE2 and the potential clinical implications of using androgen suppression to downregulate TMPRSS2 to target SARS-CoV-2. We also discuss the future directions and controversies that need to be addressed in order to establish the viability of targeting TMPRSS2 and/or ACE2 through androgen signaling regulation for COVID-19 treatment, particularly its relevance in the context of prostate cancer management.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/etiologia , Pneumonia Viral/etiologia , Neoplasias da Próstata/tratamento farmacológico , Androgênios/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/tratamento farmacológico , Serina Endopeptidases/fisiologia
3.
Adv Exp Med Biol ; 1195: 59-71, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468460

RESUMO

Herein, we deploy an in silico pipeline of structural bioinformatics, thermodynamics, and molecular dynamics to investigate the role of cortisol in circadian rhythms, biorhythms, stress response, and even sleep disorders. Our study shows that high concentrations of cortisol intercalate in the minor groove of DNA. This phenomenon widens the adjacent major grooves and provides the Clock/Bmal1 complex with more space to dock and interact with DNA. Then, the strong charges of cortisol pull the alpha helices of the Clock/Bmal1 complex and bend it inward, thus establishing stronger interactions and prolonged signaling. Our results indicate that elevated cortisol levels play an important role in stress, inflammation, and sleep disorders as a result of prolonged and stronger dsDNA - Clock/Bmal1 interactions.


Assuntos
Fatores de Transcrição ARNTL/metabolismo , Proteínas CLOCK/metabolismo , DNA/química , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Transtornos do Sono-Vigília/fisiopatologia , Estresse Psicológico/prevenção & controle , Ritmo Circadiano/genética , Ritmo Circadiano/fisiologia , Simulação por Computador , DNA/metabolismo , Humanos , Hidrocortisona/química , Inflamação/genética , Inflamação/metabolismo , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Receptores de Glucocorticoides/metabolismo , Transtornos do Sono-Vigília/genética , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia
4.
Nat Rev Endocrinol ; 16(8): 407-420, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32427949

RESUMO

Hypothalamic kisspeptin neurons serve as the nodal regulatory centre of reproductive function. These neurons are subjected to a plethora of regulatory factors that ultimately affect the release of kisspeptin, which modulates gonadotropin-releasing hormone (GnRH) release from GnRH neurons to control the reproductive axis. The presence of sufficient energy reserves is critical to achieve successful reproduction. Consequently, metabolic factors impose a very tight control over kisspeptin synthesis and release. This Review offers a synoptic overview of the different steps in which kisspeptin neurons are subjected to metabolic regulation, from early developmental stages to adulthood. We cover an ample array of known mechanisms that underlie the metabolic regulation of KISS1 expression and kisspeptin release. Furthermore, the novel role of kisspeptin neurons as active players within the neuronal circuits that govern energy balance is discussed, offering evidence of a bidirectional role of these neurons as a nexus between metabolism and reproduction.


Assuntos
Metabolismo Energético/fisiologia , Kisspeptinas/fisiologia , Reprodução/fisiologia , Animais , Dinorfinas/fisiologia , Feminino , Hormônio Liberador de Gonadotropina/fisiologia , Homeostase , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Hipotálamo/citologia , Hipotálamo/fisiologia , Kisspeptinas/genética , Hormônio Luteinizante/fisiologia , Neurocinina B/fisiologia , Neurônios/fisiologia , Ovário/fisiologia , Puberdade/fisiologia
5.
J Dairy Sci ; 103(6): 5501-5508, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32307170

RESUMO

Breeding stress-resilient livestock is a potential strategy to help mitigate the negative effect of environmental and pathogenic stressors. The hypothalamic-pituitary-adrenal axis and immune system are activated during stress events and release mediators into the circulation that help restore physiological homeostasis. The purpose of this study was to assess a comprehensive set of circulatory mediators released in response to an acute immune stress challenge to identify candidate biomarkers that can be used for the selection of stress-resilient animals. Fifteen female lambs were stress challenged with an intravenous bolus of lipopolysaccharide (LPS; 400 ng/kg), and blood was collected from the jugular vein at 0, 2, 4, and 6 h after LPS challenge to identify and monitor candidate stress biomarkers; temperature was also recorded over time. Biomarker responses were evaluated with a repeated-measures model to compare time points with baseline values. As expected, all sheep had a monophasic febrile response to LPS challenge, and cortisol increased and returned to baseline by 6 h. The cytokines tumor necrosis factor-α, IL-6, IFN-γ (proinflammatory), and IL-10 (anti-inflammatory) increased, but only tumor necrosis factor-α returned to baseline during the monitoring period. The cytokines IL-1α, IL-1ß, IL-17α (proinflammatory), and IL-4 (anti-inflammatory) did not respond to LPS challenge. All chemokines (CCL2, CCL3, CCL4, CXCL10, and IL-8) responded to LPS challenge; however, only CCL2, CCL3, CCL4, and CXCL10 increased over time, and only CCL3, CCL4, and CXCL10 returned to baseline during the monitoring period. MicroRNA (miR-145, miR-233, and miR-1246) also increased and remained elevated during the study. In summary, the LPS challenge induced a strong stress response in Rideau-Dorset sheep that could be monitored with a distinct profile of circulatory biomarkers.


Assuntos
Biomarcadores/sangue , Citocinas/sangue , Endotoxemia/sangue , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Ovinos/fisiologia , Animais , Cruzamento , Citocinas/genética , Endotoxemia/imunologia , Feminino , Hidrocortisona/sangue , Lipopolissacarídeos/efeitos adversos , MicroRNAs/genética , Ovinos/sangue , Ovinos/genética , Ovinos/imunologia , Estresse Fisiológico
6.
Gen Comp Endocrinol ; 293: 113475, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32240708

RESUMO

The vertebrate pituitary is arguably one of the most complex endocrine glands from the evolutionary, anatomical and functional perspectives. The pituitary plays a master role in endocrine physiology for the control of growth, metabolism, reproduction, water balance, and the stress response, among many other key processes. The synthesis and secretion of pituitary hormones are under the control of neurohormones produced by the hypothalamus. Under this conceptual framework, the communication between the hypophysiotropic brain and the pituitary gland is at the foundation of our understanding of endocrinology. The anatomy of the connections between the hypothalamus and the pituitary gland has been described in different vertebrate classes, revealing diverse modes of communication together with varying degrees of complexity. In this context, the evolution and variation in the neuronal, neurohemal, endocrine and paracrine modes will be reviewed in light of recent discoveries, and a re-evaluation of earlier observations. There appears to be three main hypothalamo-pituitary communication systems: 1. Diffusion, best exemplified by the agnathans; 2. Direct innervation of the adenohypophysis, which is most developed in teleost fish, and 3. The median eminence/portal blood vessel system, most conspicuously developed in tetrapods, showing also considerable variation between classes. Upon this basic classification, there exists various combinations possible, giving rise to taxon and species-specific, multimodal control over major physiological processes. Intrapituitary paracrine regulation and communication between folliculostellate cells and endocrine cells are additional processes of major importance. Thus, a more complex evolutionary picture of hypothalamo-hypophysial communication is emerging. There is currently little direct evidence to suggest which neuroendocrine genes may control the evolution of one communication system versus another. However, studies at the developmental and intergenerational timescales implicate several genes in the angiogenesis and axonal guidance pathways that may be important.


Assuntos
Sistema Hipotálamo-Hipofisário/fisiologia , Vertebrados/fisiologia , Animais , Sistema Hipotálamo-Hipofisário/ultraestrutura , Comunicação Parácrina , Filogenia
7.
Artigo em Inglês | MEDLINE | ID: mdl-32197832

RESUMO

This chapter discusses the mechanisms of action of hormonal male contraception, which suppresses the hypothalamic-pituitary-testis axis. When the intratesticular concentration of testosterone is subsequently suppressed to adequately low concentrations, spermatogenesis is arrested. Androgens are a necessary hormonal male contraceptive component because they not only suppress the hypothalamic-pituitary-testis axis, but also provide the male hormone necessary to maintain peripheral androgen functions. Past studies using testosterone alone and testosterone combined with progestins demonstrated contraceptive efficacy in the female partner at rates similar to combined hormonal female methods. Newer hormonal male contraceptive formulations and the alternative routes of administration are discussed, along with potential barriers, challenges, and opportunities for hormonal male contraceptive development. Novel methods that are safe, effective, reversible, user-friendly, and coitus-independent are intrinsic to equitably meet the various needs and limitations of an increasingly diverse population.


Assuntos
Androgênios , Anticoncepcionais Masculinos , Serviços de Planejamento Familiar/tendências , Vasectomia/métodos , Anticoncepção , Anticoncepcionais Masculinos/efeitos adversos , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Espermatogênese/fisiologia , Testículo/fisiologia , Testosterona/efeitos adversos
8.
Integr Comp Biol ; 60(1): 79-88, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32101288

RESUMO

The hypothalamic-pituitary-adrenal (HPA) axis regulates the secretion of glucocorticoids, hormones with diverse roles ranging from regulating daily metabolic demand to coping with sudden perturbations. As a result, glucocorticoids are thought to help vertebrates track their changing environments and coordinate plasticity in diverse phenotypes. While this endocrine system is highly plastic-where one individual can produce multiple phenotypes across varying environmental conditions-little is understood about the degree to which individuals, populations, or species differ in circulating glucocorticoid plasticity. Empirical research quantifying individual variation in glucocorticoid plasticity has increased in recent years, though the multiple complex roles of the HPA-axis make it challenging to generalize the extent to which individual variation in plasticity exists. I provide an overview of current findings on variation in glucocorticoids plasticity, and outline multiple types of glucocorticoid plasticity researchers should consider in future work to advance our understanding of the causes and consequences of individual variation in glucocorticoid plasticity.


Assuntos
Adaptação Fisiológica , Glucocorticoides/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Vertebrados/fisiologia , Animais
9.
Poult Sci ; 99(2): 1163-1173, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32029148

RESUMO

Variation in egg production exists in commercial turkey hens, with low egg producing hens (LEPH) costing more per egg produced than high egg producing hens (HEPH). Egg production correlates with ovulation frequency, which is governed by the hypothalamic-pituitary-gonadal (HPG) axis. Ovulation is stimulated by a preovulatory surge (PS) of progesterone and luteinizing hormone, triggered by gonadotropin releasing hormone release and inhibited by gonadotropin inhibiting hormone. Differences between LEPH and HEPH were characterized by determining HPG axis plasma hormone profiles and mRNA levels for key genes, both outside and inside of the PS (n = 3 per group). Data were analyzed with a 2-way ANOVA using the mixed models procedure of SAS. In the HPG axis, plasma progesterone levels were not affected by egg production level but were elevated during the PS. In contrast, plasma estradiol levels were higher in HEPH than in LEPH but were not associated with the PS. LEPH exhibited decreased gene expression associated with ovulation stimulation and increased gene expression associated with ovulation inhibition in the hypothalamus and pituitary. In ovarian follicle cells, LEPH displayed decreased gene expression associated with progesterone, androgen, and estradiol production in the F1 follicle granulosa cells, F5 theca interna cells, and small white follicle cells, respectively. Different degrees of stimulation and inhibition within all tissues of the HPG axis were noted between LEPH and HEPH turkey hens, with HEPH showing higher expression of genes related to ovulation and steroidogenesis.


Assuntos
Proteínas Aviárias/genética , Estradiol/sangue , Sistema Hipotálamo-Hipofisário/fisiologia , Ovário/fisiologia , Progesterona/sangue , Reprodução/fisiologia , Perus/fisiologia , Animais , Proteínas Aviárias/metabolismo , Feminino
10.
Artigo em Inglês | MEDLINE | ID: mdl-32079109

RESUMO

The aim of this study was to investigate whether the nighttime cortisol release was associated with subjective and objective sleep quality and the discrepancy between them. Forty-five healthy older adults (age range from 56 to 75 years) collected salivary samples immediately before sleep and immediately after awakening on two consecutive nights. Actigraphy was used to assess objective sleep quality and quantity. A sleep diary was used to assess subjective sleep quality. Linear mixed models were performed using subjective and objective sleep quality data from 76 nights to investigate between-subject associations. We observed that larger changes in cortisol levels between sleep onset and awakening, reflecting a healthier circadian rhythm of the Hypothalamic-Pituitary-Adrenal (HPA) axis, were associated with better subjective sleep quality, but not with objective sleep quality. Moreover, smaller changes in nighttime cortisol were associated with lower subjective sleep quality relative to objective sleep quality. All these results were observed even after controlling for important confounders such as sleep quantity, age, sex, subjective socioeconomic status, stress perception, depression, physical activity, and adherence to the salivary sampling protocol. This study demonstrates that subjective sleep quality in older people may be explained, to some extent, by the activity of the HPA axis.


Assuntos
Hidrocortisona/metabolismo , Sono/fisiologia , Idoso , Ritmo Circadiano , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/fisiologia , Saliva/química , Espanha , Fatores de Tempo
11.
Biochem Biophys Res Commun ; 523(2): 514-521, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-31898970

RESUMO

Neonatal hypoxia can induce the persisting brain dysfunctions and subsequently result in the behavioral abnormalities in adulthood. Improving mitochondrial functions were suggested as the effective strategy for brain functional recovery. In this study, we tested the effects of physical exercise, a well-established way benefits mitochondrion, for its functions to prevent hypoxia induced adult behavioral dysfunctions and the underlying molecular mechanism. Mice was induced with hypoxia and treadmill running were then administrated until the adulthood. The treadmill running resulted in the improved behavioral performance in depressive and anxiety tests together with the enhancement of hippocampal neurogenesis. We then detected treadmill running restored the mitochondrial morphology in adult neural stem cells (NSCs) as well as the ATP production in hippocampal tissue. In addition, activity of AMPK, which playing key roles in regulating mitochondrial functions, was also elevated by treadmill running. Blockage of AMPK with selective inhibitor compound C prohibited effects of treadmill running in attenuating neonatal hypoxia induced neurogenic impairment and antidepressant behavioral deficits in adulthood. In conclusion, treadmill running could prevent neonatal hypoxia induced adult antidepressant dysfunctions and neurogenic dampening via AMPK-mediated mitochondrial regulation.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Depressão/terapia , Hipóxia/psicologia , Mitocôndrias/metabolismo , Células-Tronco Neurais/citologia , Animais , Animais Recém-Nascidos , Comportamento Animal , Diferenciação Celular , Depressão/metabolismo , Depressão/patologia , Modelos Animais de Doenças , Teste de Esforço , Feminino , Hipocampo/citologia , Sistema Hipotálamo-Hipofisário/fisiologia , Hipóxia/terapia , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/metabolismo , Condicionamento Físico Animal , Sistema Hipófise-Suprarrenal/fisiologia
12.
Psychiatry Res ; 284: 112797, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31982660

RESUMO

Posttraumatic Stress Disorder (PTSD) is an anxiety disorder which occurs after a traumatic event. The NR3C1 gene codes for the Glucocorticoid Receptor, which participate in the Hypothalamic-Pituitary-Adrenal (HPA) axis and is altered in PTSD patients. To evaluate whether the NR3C1 gene expression in peripheral blood could be useful as a diagnosis biomarker, a total of 32 PTSD patients and 59 healthy controls were analyzed with quantitative RT-PCR. Also, to assess if NR3C1 dysregulation is associated with hypocortisolism in PTSD patients, serum cortisol was quantified by ELISA in a subset of these samples. Significant NR3C1 over-expression was found in PTSD patients compared with controls, and this was higher in patients with acute PTSD. The Area Under the Curve (AUC) of NR3C1 gene expression was 0.797. The sensibility and specificity of NRC1 gene expression to diagnose PTSD was 62.5% and 89.8%, respectively. We also found that an up-regulation of NR3C1 increased the risk for being diagnosed with PTSD (OR= 12.8, 95%, CI 4-41.4). Finally, the NR3C1 gene expression was inversely related with serum cortisol in PTSD patients. The present results suggest that NR3C1 gene expression could be a promising biomarker for PTSD diagnosis and estimate the risk for disease development.


Assuntos
Marcadores Genéticos/genética , Receptores de Glucocorticoides/genética , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , Feminino , Expressão Gênica , Humanos , Hidrocortisona/genética , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , México/epidemiologia , Sistema Hipófise-Suprarrenal/fisiologia , Receptores de Glucocorticoides/biossíntese , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Regulação para Cima/fisiologia
13.
J Neurosci ; 40(1): 12-21, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31896560

RESUMO

Over the last 50 years, the concept of stress has evolved significantly, and our understanding of the underlying neurobiology has expanded dramatically. Rather than consider stress biology to be relevant only under unusual and threatening conditions, we conceive of it as an ongoing, adaptive process of assessing the environment, coping with it, and enabling the individual to anticipate and deal with future challenges. Though much remains to be discovered, the fundamental neurocircuitry that underlies these processes has been broadly delineated, key molecular players have been identified, and the impact of this system on neuroplasticity has been well established. More recently, we have come to appreciate the critical interaction between the brain and the rest of the body as it pertains to stress responsiveness. Importantly, this system can become overloaded due to ongoing environmental demands on the individual, be they physical, physiological, or psychosocial. The impact of this overload is deleterious to brain health, and it results in vulnerability to a range of brain disorders, including major depression and cognitive deficits. Thus, stress biology is one of the best understood systems in affective neuroscience and is an ideal target for addressing the pathophysiology of many brain-related diseases. The story we present began with the discovery of glucocorticoid receptors in hippocampus and has extended to other brain regions in both animal models and the human brain with the further discovery of structural and functional adaptive plasticity in response to stressful and other experiences.


Assuntos
Encéfalo/fisiologia , Glucocorticoides/fisiologia , Transtornos do Humor/fisiopatologia , Estresse Fisiológico/fisiologia , Estresse Psicológico/fisiopatologia , Adaptação Fisiológica/fisiologia , Animais , Endocanabinoides/fisiologia , Epigênese Genética , Retroalimentação Fisiológica , Fator 2 de Crescimento de Fibroblastos/fisiologia , Fator 2 de Crescimento de Fibroblastos/uso terapêutico , Regulação da Expressão Gênica/fisiologia , Hormônios/fisiologia , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Acontecimentos que Mudam a Vida , Modelos Neurológicos , Modelos Psicológicos , Transtornos do Humor/etiologia , Transtornos do Humor/psicologia , Proteínas do Tecido Nervoso/fisiologia , Plasticidade Neuronal , Sistema Hipófise-Suprarrenal/fisiologia , Psicofisiologia , Receptores de Superfície Celular/fisiologia , Determinantes Sociais da Saúde
14.
Int J Behav Med ; 27(3): 337-342, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31900867

RESUMO

In recent years, research in behavioral medicine has become increasingly focused on understanding how chronic and acute exposure to stress impacts health outcomes. During stress, the body's physiological stress systems are activated. These systems closely interact with the immune system and are, thus, importantly implicated in the onset and maintenance of disease states. While much of the research in behavioral medicine that has investigated the effects of stress on disease has focused on the role of the hypothalamic-pituitary-adrenal axis and its downstream biomarker, cortisol, it is evident that the autonomic nervous system (ANS) also plays a crucial role in both the biological stress process and the manifestation and maintenance of stress-related symptoms. In recent years salivary alpha-amylase (sAA) has emerged as a valid and reliable marker of ANS activity in stress research and is therefore an important biomarker to consider in behavioral medicine. In this commentary, we will highlight research relevant for behavioral medicine that has utilized sAA measurements, both basally, and in response to stress, to examine ANS function in clinical populations. We will additionally summarize findings from studies that have examined the effects of various targeted interventions on changes in sAA levels. Through this, our aim is to present evidence that sAA can serve as a feasible biomarker of ANS (dys)function in health and disease. To this end, we will also highlight important methodological considerations for readers to keep in mind when including sAA assessments in their own studies. The overarching goal of this brief commentary is to highlight how a multidimensional approach toward physiological stress measurement can allow researchers to develop a better understanding of physical health and disease states.


Assuntos
Saliva/química , alfa-Amilases Salivares/metabolismo , Estresse Fisiológico/fisiologia , Sistema Nervoso Autônomo/fisiologia , Medicina do Comportamento , Biomarcadores/metabolismo , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia
15.
Am J Physiol Endocrinol Metab ; 318(2): E297-E309, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31770013

RESUMO

As a model of extreme conditions, eight healthy women, part of a 40-member Nepal mountain-climbing expedition, were monitored for dynamic endocrine adaptations. Endocrine measurements were made at frequent intervals over a 6-10-h period at four altitudes: 450 m, 4,800 m (base camp), 6,050 m, and again at 4,800 m (on descent) after an acclimatization (A) period (4,800 mA). Quantified hormones were growth hormone (GH), prolactin (PROL), cortisol (Cort), thyroid-stimulating hormone (TSH), and free thyroxine. These hormones are important to the anabolic/catabolic balance of the body, and are vital to growth, homeostasis, hypothalamic inhibition, regulation of stress, and metabolism. A key secondary question was the degree to which acclimatization can stabilize hormonal disruption. On the basis of statistical false discovery rates, the present analyses unveil marked adaptive changes in the thyroid axis at the level of pulsatile secretion of the pituitary hormone TSH and its downstream product, free thyroxine; strong effects on the mass of GH, TSH, Cort, and PROL secretion per burst; and prominent pulsatile frequency disruption and recovery for PROL and Cort. Because pulsatility changes reflect de facto perturbations in hypothalamo-pituitary control mechanisms, the present data introduce the concept of both frequency- and amplitude-dependent adaptive control of brain-pituitary neuroendocrine signals under conditions of extreme altitude exertion and exposure.


Assuntos
Altitude , Sistema Endócrino/fisiologia , Aclimatação , Adaptação Fisiológica , Adulto , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Hipóxia/metabolismo , Montanhismo , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiologia , Prolactina/sangue , Hormônios Tireóideos/sangue
16.
Psychoneuroendocrinology ; 111: 104474, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31731137

RESUMO

Using data from a large international sample (N = 385) of first-time expectant parents, the current analysis investigated whether parents demonstrated diurnal cortisol linkage in late pregnancy and whether self-reported psychological stress moderated this linkage. At approximately 36 weeks gestation, mothers and fathers collected saliva samples in their home at three times on two consecutive days and reported on their psychological stress. Results from multilevel models indicated that there was significant positive within-couple diurnal cortisol linkage on average for the whole sample. However, this linkage was moderated by maternal self-reported psychological stress. Specifically, for couples with higher maternal psychological stress, cortisol linkage was strong. Conversely, for couples with lower maternal psychological stress, maternal and paternal cortisol were unrelated. These findings suggest that among higher-maternal-stress couples, lower paternal cortisol may buffer maternal cortisol, whereas higher paternal cortisol may amplify maternal cortisol. Our results support the idea that interpersonal psychological and physiological stress in close relationships is interdependent and mutually influenced. Further, our findings contribute to the field's understanding of interpersonal processes during pregnancy, which may have health-related implications in the prenatal and postnatal periods for both parents and the developing child.


Assuntos
Hidrocortisona/análise , Terceiro Trimestre da Gravidez/psicologia , Estresse Psicológico/metabolismo , Adulto , Ansiedade , Pai/psicologia , Feminino , Idade Gestacional , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Relações Interpessoais , Masculino , Mães/psicologia , Sistema Hipófise-Suprarrenal/fisiologia , Gravidez , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal , Estudos Prospectivos , Saliva/química , Autorrelato , Estresse Fisiológico/fisiologia
17.
Dev Cogn Neurosci ; 40: 100716, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31704654

RESUMO

It is well-established that children from low-income, under-resourced families are at increased risk of altered social development. However, the biological mechanisms by which poverty-related adversities can "get under the skin" to influence social behavior are poorly understood and cannot be easily ascertained using human research alone. This study utilized a rodent model of "scarcity-adversity," which encompasses material resource deprivation (scarcity) and reduced caregiving quality (adversity), to explore how early-life scarcity-adversity causally influences social behavior via disruption of developing stress physiology. Results showed that early-life scarcity-adversity exposure increased social avoidance when offspring were tested in a social approach test in peri-adolescence. Furthermore, early-life scarcity-adversity led to blunted hypothalamic-pituitary-adrenal (HPA) axis activity as measured via adrenocorticotropic hormone (ACTH) and corticosterone (CORT) reactivity following the social approach test. Western blot analysis of brain tissue revealed that glucocorticoid receptor levels in the dorsal (but not ventral) hippocampus and medial prefrontal cortex were significantly elevated in scarcity-adversity reared rats following the social approach test. Finally, pharmacological repletion of CORT in scarcity-adversity reared peri-adolescents rescued social behavior. Our findings provide causal support that early-life scarcity-adversity exposure negatively impacts social development via a hypocorticosteronism-dependent mechanism, which can be targeted via CORT administration to rescue social behavior.


Assuntos
Corticosterona/uso terapêutico , Sistema Hipotálamo-Hipofisário/fisiologia , Comportamento Social , Adolescente , Animais , Criança , Corticosterona/farmacologia , Feminino , Humanos , Masculino , Ratos , Estresse Psicológico
18.
PLoS One ; 14(9): e0223168, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31568479

RESUMO

AIMS: Alcohol use is associated with both positive and negative effects on individual cardiovascular risk factors, depending upon which risk factor is assessed. The present analysis uses a summative multisystem index of biologic risk, known as allostatic load (AL), to evaluate whether the overall balance of alcohol-associated positive and negative cardiovascular risk factors may be favorable or unfavorable. METHODS: This analysis included 1255 adults from the Midlife in the United States (MIDUS) biomarker substudy. Participants, average age 54.5 (±11) years, were divided into 6 alcohol-use categories based on self-reported drinking habits. Current non-drinkers were classified as lifelong abstainers and former light drinkers, former moderate drinkers, or former heavy drinkers. Current alcohol users were classified as light, moderate, or heavy drinkers. A total AL score was calculated using 24 biomarkers grouped into 7 physiologic systems including cardiovascular, inflammation, glucose metabolism, lipid metabolism, sympathetic and parasympathetic nervous systems, and the hypothalamic-pituitary-adrenal axis. Mixed-effects regression models were fit to determine the relationship between alcohol use categories and AL with controls for covariates that may influence the relationship between alcohol use and AL. RESULTS: 468 (37.6%) individuals were current non-drinkers while 776 (62.4%) were current drinkers. In adjusted mixed-effects regression models, all 3 groups of current drinkers had significantly lower average AL scores than the lifelong abstainer/former light drinker group (light: -0.23, 95% CI -0.40, -0.07, p < 0.01; moderate: -0.20, 95% CI -0.38, -0.02, p < 0.05; heavy: -0.30, 95% CI -0.57, -0.04, p < 0.05), while the average AL scores of former moderate and former heavy drinkers did not differ from the lifelong abstainer/former light drinker group. CONCLUSIONS: Current alcohol use is associated cross-sectionally with a favorable multisystem physiologic score known to be associated with better long-term health outcomes, providing evidence in support of long-term health benefits related to alcohol consumption.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Alostase/efeitos dos fármacos , Doenças Cardiovasculares/epidemiologia , Etanol/farmacologia , Redes e Vias Metabólicas/efeitos dos fármacos , Adulto , Idoso , Alostase/fisiologia , Biomarcadores/metabolismo , Doenças Cardiovasculares/diagnóstico , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Redes e Vias Metabólicas/fisiologia , Pessoa de Meia-Idade , Sistema Nervoso Parassimpático/efeitos dos fármacos , Sistema Nervoso Parassimpático/fisiologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/fisiologia , Análise de Regressão , Projetos de Pesquisa , Fatores de Risco , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Estados Unidos/epidemiologia
19.
Curr Psychiatry Rep ; 21(9): 93, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31478105

RESUMO

PURPOSE OF REVIEW: This article reviews the relationship of the microbiome, the gut-brain axis, and depression. It also will review factors which can influence this relationship, such as chronic stress, medications, and the Western diet typically consumed by adolescents. RECENT FINDINGS: Changes in the gut microbiome increase the release of microbial lipopolysaccharides (LPS) which activate a gut inflammatory response. Gut pro-inflammatory cytokines stimulate the afferent vagal nerve which in turn impacts the hypothalamic-pituitary-adrenal (HPA) axis inducing symptoms associated with depression. Recent research suggests that gut inflammation can induce neuroinflammation which, in turn, stimulates microglia activation and the kynurenine pathway and can activate systemic inflammation-inducing depressive symptoms. Promoting a healthy diet and lifestyle changes, limiting exposure to pesticides, limiting medications that affect the microbiome and the use of such things pre/probiotics and other interventions may complement existing efforts to curb the rise in depression. Alternative and complementary therapies may serve as effective treatments in adolescents with depression.


Assuntos
Encéfalo/fisiologia , Depressão/microbiologia , Depressão/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Saúde Mental , Adolescente , Encéfalo/patologia , Encéfalo/fisiopatologia , Depressão/imunologia , Depressão/patologia , Dieta Saudável , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia , Cinurenina/metabolismo , Microglia/imunologia , Sistema Hipófise-Suprarrenal/fisiologia
20.
J Vet Intern Med ; 33(5): 2286-2293, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31489708

RESUMO

BACKGROUND: Transient hypothalamic-pituitary-adrenal axis dysfunction occurs in critically ill foals with sepsis and neonatal maladjustment syndrome (NMS). Cortisol is the most commonly measured steroid. However, a complex interaction of various steroid compounds might play a role in pathophysiology of this disorder. OBJECTIVE: To identify steroid compounds present at high concentrations at birth that rapidly and steadily decrease within the first 7 days of life in healthy foals and that might be supportive diagnosis of NMS and other neonatal disorders. ANIMALS: Ten healthy neonatal Quarter Horse foals (5 females and 5 males). METHODS: Prospective study. Blood was collected in heparinized tubes within 30 minutes after birth, and at 12, 24, 48, 72, 96, 120, 144, and 168 hours of age. Plasma was separated and a panel of steroid compounds was analyzed using liquid chromatography-mass spectrometry. A nonlinear regression model was used to determine decay concentrations over time. Confidence intervals (CIs) were calculated and significance was set a P ≤ .05. RESULTS: Five compounds were identified: pregnenolone, progesterone, deoxycorticosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. Pregnenolone and progesterone concentrations rapidly decreased by 24 hours of age and remained low throughout the first 7 days of life. Their half-life (95% CI) was short at 3.7 (3.4, 4.0) and 4.5 (2.8, 6.1) hours, respectively. No statistical differences in the concentrations of these compounds were found between males and females. CONCLUSIONS AND CLINICAL RELEVANCE: Progesterone might be a useful marker for identifying continuous endogenous production of neuroactive steroids in foals with suspected NMS and other neonatal diseases.


Assuntos
Animais Recém-Nascidos/sangue , Cavalos/sangue , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Animais , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/sangue , Desoxicorticosterona/sangue , Feminino , Masculino , Pregnenolona/sangue , Progesterona/sangue , Estudos Prospectivos
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