RESUMEN
The relationship between events occurring during intrauterine development and later-life predisposition to long-term disease, has been described. The fetus responds to excess intrauterine exposure to high levels of corticosteroids, modifying their physiological development and stopping their growth. Fetal exposure to elevated levels of either endogenous (alterations in fetal hypothalamic-pituitary-adrenal axis) or synthetic corticosteroids, is one model of early-life adversity; to developing adult disease. At the molecular level, there are transcriptional changes in metabolic and growth pathways. Epigenetic mechanisms participate in transgenerational inheritance, not genomic. Exposures that change 11ß-hydroxysteroid dehydrogenase type 2 enzyme methylation status in the placenta can result in transcriptional repression of the gene, causing the fetus to be exposed to higher levels of cortisol. More precise diagnosis and management of antenatal corticosteroids for preterm birth, would potentially decrease the risk of long-term adverse outcomes. More studies are needed to understand the potential roles of factors to alter fetal corticosteroid exposure. Long-term infant follow-up is required to determine whether methylation changes in placenta may represent useful biomarkers of later disease risk. This review, summarize recent advances in the programming of fetal effects of corticosteroid exposure, the role of corticosteroids in epigenetic gene regulation of placental 11ß-hydroxysteroid dehydrogenase type 2 enzyme expression and transgenerational effects.
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Placenta , Nacimiento Prematuro , Adulto , Embarazo , Femenino , Recién Nacido , Humanos , Placenta/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/genética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/farmacología , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal/fisiología , Nacimiento Prematuro/inducido químicamente , Feto , Glucocorticoides/efectos adversos , Epigénesis Genética , Desarrollo Fetal/fisiologíaRESUMEN
Diabetic patients are more affected by depression than non-diabetics, and this is related to greater treatment resistance and associated with poorer outcomes. This increase in the prevalence of depression in diabetics is also related to hyperglycemia and hypercortisolism. In diabetics, the hyperactivity of the HPA axis occurs in parallel to gut dysbiosis, weakness of the intestinal permeability barrier, and high bacterial-product translocation into the bloodstream. Diabetes also induces an increase in the permeability of the blood-brain barrier (BBB) and Toll-like receptor 4 (TLR4) expression in the hippocampus. Furthermore, lipopolysaccharide (LPS)-induced depression behaviors and neuroinflammation are exacerbated in diabetic mice. In this context, we propose here that hypercortisolism, in association with gut dysbiosis, leads to an exacerbation of hippocampal neuroinflammation, glutamatergic transmission, and neuronal apoptosis, leading to the development and aggravation of depression and to resistance to treatment of this mood disorder in diabetic patients.
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Síndrome de Cushing , Trastorno Depresivo , Diabetes Mellitus Experimental , Humanos , Ratones , Animales , Eje Cerebro-Intestino , Sistema Hipotálamo-Hipofisario/fisiología , Enfermedades Neuroinflamatorias , Disbiosis , Sistema Hipófiso-Suprarrenal/fisiologíaRESUMEN
AIMS: During illnesses caused by infectious diseases, a suite of brain-mediated responses called sickness syndrome occurs, triggering behavioral and physiological changes. This study investigated whether ghrelin modulates sickness syndrome induced by systemic administration of lipopolysaccharide (LPS). MAIN METHODS: Male Wistar rats were pretreated with vehicle or [D-lys3]-GHRP-6, a ghrelin receptor GHS-R1 antagonist (20 nmol, i.c.v), 30 min before injection of LPS (200 µg/kg, i.p.) or sterile saline. We investigated the behavioral effects in male rats after LPS administration by screening for depressive-like behavior, locomotor activity alterations, and corticosterone release. Changes in body temperature were measured using a biotelemetry probe preimplanted in the peritoneal cavity to evaluate the effect of ghrelin on the thermoregulatory response during immunological challenge. KEY FINDINGS: Pretreatment with [D-lys3]-GHRP-6 blunted most of the assessed parameters related to sickness syndrome, including social withdrawal, anhedonia, depressive-like behavior, and anorexia, reduced the activation of the HPA axis, but did not alter LPS-induced fever. SIGNIFICANCE: Our findings suggest that ghrelin centrally mediates the sickness behavior and activation of HPA, as a ghrelin receptor antagonist attenuates social withdrawal, anhedonia, depressive-like behavior, anorexia, and HPA activation in response to LPS.
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Sistema Hipotálamo-Hipofisario/fisiología , Conducta de Enfermedad/efectos de los fármacos , Lipopolisacáridos/toxicidad , Trastornos Mentales/prevención & control , Oligopéptidos/farmacología , Receptores de Ghrelina/antagonistas & inhibidores , Animales , Temperatura Corporal , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Conducta de Enfermedad/fisiología , Locomoción , Masculino , Trastornos Mentales/inducido químicamente , Trastornos Mentales/metabolismo , Trastornos Mentales/patología , Ratas , Ratas WistarRESUMEN
The hypothalamus-pituitary-thyroid-axis (HPT) is one of the main neuroendocrine axes that control energy expenditure. The activity of hypophysiotropic thyrotropin releasing hormone (TRH) neurons is modulated by nutritional status, energy demands and stress, all of which are sex dependent. Sex dimorphism has been associated with sex steroids whose concentration vary along the life-span, but also to sex chromosomes that define not only sexual characteristics but the expression of relevant genes. In this review we describe sex differences in basal HPT axis activity and in its response to stress and to metabolic challenges in experimental animals at different stages of development, as well as some of the limited information available on humans. Literature review was accomplished by searching in Pubmed under the following words: "sex dimorphic" or "sex differences" or "female" or "women" and "thyrotropin" or "thyroid hormones" or "deiodinases" and "energy homeostasis" or "stress". The most representative articles were discussed, and to reduce the number of references, selected reviews were cited.
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Metabolismo Energético/fisiología , Sistema Hipotálamo-Hipofisario/fisiología , Caracteres Sexuales , Estrés Fisiológico/fisiología , Glándula Tiroides/fisiología , Adaptación Fisiológica/fisiología , Animales , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Suicide behavior (SB) has been highly associated with the response to stress and the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to summarize the results obtained in genetic studies that analyzed the HPA axis-stress pathway and SB through a systematic review. METHODS: We performed an online search in PubMed, EBSCO, Web of Science, Scopus, and PsycoInfo databases up to May 2021. We followed the PRISMA guidelines for systematic reviews. We included case-control and expression studies that provided data on mRNA expression and single-nucleotide polymorphisms of genes associated with SB. RESULTS: A total of 21,926 individuals participated across 41 studies (not repeats); 34 studies provided data on single-nucleotide polymorphisms in 21,284 participants and 11 studies reported data on mRNA expression in 1034 participants. Ten genes were identified: FKBP5, CRH, CRHBP, CRHR1, CRHR2, NR3C1, NR3C2, SKA2, MC2R, and POMC. CONCLUSIONS: Our findings suggest that key stress pathway genes are significantly associated with SB and show potential as biomarkers for SB.
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Estudios de Asociación Genética , Sistema Hipotálamo-Hipofisario/fisiología , Estrés Psicológico/genética , Suicidio/psicología , Regulación de la Expresión Génica/genética , Interacción Gen-Ambiente , Humanos , Polimorfismo de Nucleótido Simple/genética , Estrés Psicológico/psicología , Prevención del SuicidioRESUMEN
Poverty is a chronic stressor associated with disruptions in psychophysiological development during adolescence. This study examined associations of chronic poverty and income changes experienced from pre- to mid-adolescence with hypothalamic-pituitary-adrenal (HPA) axis stress responses in late adolescence. Participants (N = 229) were adolescents of Mexican-origin (48.7% female). Household income (converted to income-to-needs ratios) was assessed annually when children were 10-16 years old. At 17 years, adolescents completed Cyberball, a social exclusion simulation task while undergoing a functional magnetic resonance imaging scan. Saliva samples were collected prior to and five times over a 50-minute period following the scan, from which salivary cortisol was assayed. Results showed that differential trajectories of poverty from ages 10-16 predicted HPA axis activity at age 17. Relative to others, distinct HPA suppression (hyporeactivity) was demonstrated by youth who started adolescence in deep poverty and were still living in poverty at age 16 despite experiencing some income gains. Youth from more economically secure families evinced typical cortisol increases following the lab stressor. These results suggest that subsequent HPA functioning varies as a function of economic status throughout adolescence, and that efforts to increase family income may promote healthy HPA functioning for youths in the most impoverished circumstances.
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Hidrocortisona , Pobreza , Estrés Psicológico , Adolescente , Niño , Femenino , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Masculino , México/etnología , Sistema Hipófiso-Suprarrenal/fisiología , Pobreza/psicología , Pobreza/estadística & datos numéricos , Saliva/química , Estrés Psicológico/fisiopatologíaRESUMEN
The ability to successfully cope with stress is known as 'resilience', and resilient individuals are less prone to develop psychopathologies. Understanding the neurobiological mechanisms of resilience may be instrumental to improve current therapies and benefit high-risk subjects. This review summarizes the complex interplay that exists between physiological and pathological responses to stressful events and the nociceptin/orphanin FQ (N/OFQ) - N/OFQ receptor (NOP) system, including: the effects of stress in regulating N/OFQ release and NOP expression; the ability of the N/OFQ-NOP system to modulate the hypothalamic-pituitary-adrenal axis; behavioral studies; and evidence in humans correlating this peptidergic system with psychopathologies. Available findings support the view that N/OFQ signaling stimulates the hypothalamic-pituitary-adrenal axis, thus increasing stress circulating hormones and corticotropin-releasing factor signaling. Additionally, activation of the NOP receptor inhibits monoamine transmission, including 5-HT, and this may contribute to maladaptive outcomes of stress. Ultimately, the N/OFQ system seems to have an important role in stress vulnerability, and blockade of NOP signaling may provide an innovative strategy for the treatment of stress related psychopathologies.
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Péptidos Opioides/fisiología , Receptores Opioides/fisiología , Estrés Psicológico/etiología , Animales , Humanos , Sistema Hipotálamo-Hipofisario/fisiología , Antagonistas de Narcóticos/farmacología , Sistema Hipófiso-Suprarrenal/fisiología , Estrés Psicológico/tratamiento farmacológico , Receptor de Nociceptina , NociceptinaRESUMEN
BACKGROUND/AIMS: Furosemide is a loop diuretic widely used in clinical practice for the treatment of oedema and hypertension. The aim of this study was to determine physiological and molecular changes in the hypothalamic-neurohypophysial system as a consequence of furosemide-induced sodium depletion. METHODS: Male rats were sodium depleted by acute furosemide injection (10 and 30 mg/kg) followed by access to low sodium diet and distilled water for 24 h. The renal and behavioural consequences were evaluated, while blood and brains were collected to evaluate the neuroendocrine and gene expression responses. RESULTS: Furosemide treatment acutely increases urinary sodium and water excretion. After 24 h, water and food intake were reduced, while plasma angiotensin II and corticosterone were increased. After hypertonic saline presentation, sodium-depleted rats showed higher preference for salt. Interrogation using RNA sequencing revealed the expression of 94 genes significantly altered in the hypothalamic paraventricular nucleus (PVN) of sodium-depleted rats (31 upregulated and 63 downregulated). Out of 9 genes chosen, 5 were validated by quantitative PCR in the PVN (upregulated: Ephx2, Ndnf and Vwf; downregulated: Caprin2 and Opn3). The same genes were also assessed in the supraoptic nucleus (SON, upregulated: Tnnt1, Mis18a, Nr1d1 and Dbp; downregulated: Caprin2 and Opn3). As a result of these plastic transcriptome changes, vasopressin expression was decreased in PVN and SON, whilst vasopressin and oxytocin levels were reduced in plasma. CONCLUSIONS: We thus have identified novel genes that might regulate vasopressin gene expression in the hypothalamus controlling the magnocellular neurons secretory response to body sodium depletion and consequently hypotonic stress.
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Diuréticos/farmacología , Furosemida/farmacología , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sodio/metabolismo , Transcriptoma/efectos de los fármacos , Equilibrio Hidroelectrolítico/efectos de los fármacos , Animales , Sistema Hipotálamo-Hipofisario/fisiología , Masculino , Oxitocina/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas , Ratas Wistar , Factores de Tiempo , Transcriptoma/fisiología , Vasopresinas/metabolismo , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
PURPOSE: To evaluate factors that could potentially affect the hypothalamic-pituitary adrenal (HPA) axis response to insulin-induced hypoglycemia in children without history or symptoms of adrenal insufficiency and to propose a cut-off value to define a normal response in this population. METHODS: Exploratory single-center study involving 78 children that prospectively underwent insulin tolerance test (ITT) for suspected growth hormone (GH) deficiency. METHODS: Glucose, cortisol, GH, adrenocorticotrophic hormone (ACTH), epinephrine and norepinephrine levels were measured at baseline and after insulin-induced hypoglycemia. Serum cortisol was measured using Access automated immunoassay. RESULTS: Mean (range) basal morning serum cortisol of 8 (2.2-19.5) µg/dL/222 (61-542) nmol/L increased after hypoglycemia to 20.5 (14.6-29.5) µg/dL/570 nmol/L (405-819) nmol/L. Peak serum cortisol levels of 14.6 µg/dL (405 nmol/L) and 15.4 µg/dL (428 nmol/L) corresponded to the 2.5th and 5th percentiles, respectively. Peak serum cortisol correlated with peak plasma epinephrine (r = 0.367; P = 0.0014) but did not correlate with age, BMI-SD or peak serum GH. Children with intact and abnormal GH responses presented similar mean peak serum cortisol levels (20.0 vs. 20.6 µg/dL/555 vs. 572 nmol/L; P = 0.21). CONCLUSION: Our data indicate that the current cut-off to define normal HPA axis response in children after insulin-induced hypoglycemia warrants reevaluation to avoid over-diagnosis of adrenal insufficiency. Our results suggest that peak serum cortisol levels ≥ 15.4 µg/dL (428 nmol/L) in children undergoing ITT might represent a normal cortisol response to stress, regardless of age, BMI or GH secretory capacity.
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Hidrocortisona/sangre , Hipoglucemia , Sistema Hipotálamo-Hipofisario , Insulina , Monitoreo Fisiológico/métodos , Insuficiencia Suprarrenal/diagnóstico , Hormona Adrenocorticotrópica/sangre , Glucemia/análisis , Niño , Epinefrina/sangre , Femenino , Voluntarios Sanos , Humanos , Hipoglucemia/sangre , Hipoglucemia/inducido químicamente , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/metabolismo , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/fisiología , Insulina/administración & dosificación , Insulina/metabolismo , Masculino , Uso Excesivo de los Servicios de Salud/prevención & control , Valores de ReferenciaRESUMEN
Growth is the task of children. We review the normal process of linear growth from the fetus through adolescence and note that growth is the result of age- and gender-dependent interactions among key genetic, environmental, dietary, socioeconomic, developmental, behavioral, nutritional, metabolic, biochemical, and hormonal factors. We then define the wide range of normative data at each stage of growth and note that a pattern within this range is generally indicative of good general health and that growth significantly slower than this range may lead to growth faltering and subsequent short stature. Although not often emphasized, we detail how to properly measure infants and children because height velocity is usually determined from two height measurements (both relatively large values) to calculate the actual height velocity (a relatively much smaller number in comparison). Traditionally the physiology of growth has been taught from an endocrine-centric point-of-view. Here we review the hypothalamic-pituitary-end organ axes for the GH/IGF-1 and gonadal steroid hormones (hypothalamic-pituitary-gonadal axis), both during "mini"-puberty as well as at puberty. However, over the past few decades much more emphasis has been placed on the growth plate and its many interactions with the endocrine system but also with its own intrinsic physiology and gene mutations. These latter, whether individually (large effect size) or in combination with many others including endocrine system-based, may account in toto for meaningful differences in adult height. The clinical assessment of children with short stature includes medical, social and family history, physical exam and importantly proper interpretation of the growth curve. This analysis should lead to judicious use of screening laboratory and imaging tests depending on the pre-test probability (Bayesian inference) of a particular diagnosis in that child. In particular for those with no pathological features in the history and physical exam and a low, but normal height velocity, may lead only to a bone age exam and reevaluation (re-measurement), perhaps 6 months later. he next step depends on the comfort level of the primary care physician, the patient, and the parent; that is, whether to continue with the evaluation with more directed, more sophisticated testing, again based on Bayesian inference or to seek consultation with a subspecialist pediatrician based on the data obtained. This is not necessarily an endocrinologist. The newest area and the one most in flux is the role for genetic testing, given that growth is a complex process with large effect size for single genes but smaller effect sizes for multiple other genes which in the aggregate may be relevant to attained adult height. Genetics is a discipline that is rapidly changing, especially as the cost of exome or whole gene sequencing diminishes sharply. Within a decade it is quite likely that a genetic approach to the evaluation of children with short stature will become the standard, truncating the diagnostic odyssey and be cost effective as fewer biochemical and imaging studies are required to make a proper diagnosis.
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Trastornos del Crecimiento/diagnóstico , Crecimiento/fisiología , Adolescente , Determinación de la Edad por el Esqueleto/métodos , Teorema de Bayes , Estatura/genética , Estatura/fisiología , Niño , Preescolar , Femenino , Interacción Gen-Ambiente , Pruebas Genéticas/tendencias , Crecimiento/genética , Trastornos del Crecimiento/etiología , Hormona del Crecimiento/metabolismo , Placa de Crecimiento/fisiología , Humanos , Sistema Hipotálamo-Hipofisario/fisiología , Lactante , Recién Nacido , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Anamnesis , Examen Físico , Pubertad/fisiología , Factores SexualesRESUMEN
Previous studies indicate that leptin regulates the hypothalamic-pituitary-thyroid (HPT) axis via direct and indirect mechanisms. The indirect mechanism involves leptin action in pro-opiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurones. These cells innervate the paraventricular nucleus of the hypothalamus (PVH) where they modulate hypophysiotrophic thyrotrophin-releasing hormone (TRH)-producing neurones. The direct mechanism involves the expression of leptin receptor (LepR) in a subpopulation of PVH TRH neurones. However, to our knowledge, the existence of LepR in PVH TRH neurones of mice has not been clearly confirmed. Therefore, we investigated possible species-specific differences between rats and mice with respect to the mechanisms recruited by leptin to regulate the HPT axis. We observed that an acute leptin injection induced phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a marker of leptin-responsive cells, in 46.2 ± 8.0% of PVH proTRH immunoreactive neurones in rats. By contrast, an insignificant number of proTRH positive neurones in the mouse PVH co-expressed leptin-induced pSTAT3 or LepR. Similarly, central leptin injection increased the percentage of PVH proTRH neurones containing cAMP response element-binding protein phosphorylation in rats, but not in mice. We investigated the innervation of AgRP and POMC axons in the PVH and observed that rats exhibited a denser POMC innervation in the PVH compared to mice, whereas rats and mice showed similar density of AgRP axons in the PVH. In conclusion, rats and mice exhibit important species-specific differences in the direct and indirect mechanisms used by leptin to regulate the HPT axis.
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Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Leptina/farmacología , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Glándula Tiroides/efectos de los fármacos , Animales , Sistema Hipotálamo-Hipofisario/fisiología , Leptina/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas , Ratas Long-Evans , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Especificidad de la Especie , Glándula Tiroides/fisiología , Hormona Liberadora de Tirotropina/metabolismoRESUMEN
There is a lack of information correlating low adiposity with hypertension experienced by Spontaneous Hypertensive Rats (SHR) or overweight and normotension in Wistar-Kyoto (WKY). We aimed to investigate this lipodystrophy phenomenon by measuring fluorescence lifetime (FLIM), optical redox ratio (ORR), serum levels of hypothalamic-pituitary-adrenal (HPA) and/or hypothalamic-pituitary-thyroid (HPT) hormones axes between Wistar, WKY and SHR before and after establishment of hypertension. Under high blood pressure, we evaluated serum adipokines. Brown adipose tissue was characterized as lower ORR and shorter FLIM compared to white adipose tissue. HPT axis showed a crucial role in the SHR adipose tissue configuration by attenuating whitening. The increased adiposity in WKY may act as a preventive agent for hypertension, since SHR, with low adiposity, establishes the disease. The hypertensive environment can highlight key adipokines that may result in new therapeutic approaches to the treatment of adiposity dysfunctions and hypertension.
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Tejido Adiposo Pardo/fisiología , Tejido Adiposo/fisiología , Hipertensión , Lipodistrofia , Adipoquinas/sangre , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/metabolismo , Tejido Adiposo Pardo/diagnóstico por imagen , Animales , Presión Sanguínea/fisiología , Hipertensión/complicaciones , Hipertensión/diagnóstico por imagen , Hipertensión/metabolismo , Hipertensión/fisiopatología , Sistema Hipotálamo-Hipofisario/diagnóstico por imagen , Sistema Hipotálamo-Hipofisario/fisiología , Lipodistrofia/diagnóstico por imagen , Lipodistrofia/etiología , Lipodistrofia/fisiopatología , Masculino , Microscopía Fluorescente/métodos , Oxidación-Reducción , Sistema Hipófiso-Suprarrenal/diagnóstico por imagen , Sistema Hipófiso-Suprarrenal/fisiología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/fisiologíaRESUMEN
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.
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Marcadores Genéticos/genética , Receptores de Glucocorticoides/genética , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/genética , Adulto , Femenino , Expresión Génica , Humanos , Hidrocortisona/genética , Sistema Hipotálamo-Hipofisario/fisiología , Masculino , México/epidemiología , Sistema Hipófiso-Suprarrenal/fisiología , Receptores de Glucocorticoides/biosíntesis , Factores de Riesgo , Trastornos por Estrés Postraumático/epidemiología , Regulación hacia Arriba/fisiologíaRESUMEN
Glucocorticoids participate in the behavioral and physiological responses generated under stressful circumstances coming from different sources-physical and/or psychological. In mammals, the increases of these hormones are mediated by the activation of the hypothalamic-pituitary-adrenal axis. This response occurs after exposure to novel and unpredictable situations that lead to the loss of homeostasis, for example, a direct encounter with predators or their cues. However, the relationship between the physiological and behavioral responses is still a complex issue in vertebrates. We evaluate the effects of an experimental manipulation of glucocorticoid levels on the generation of the behavioral and physiological response to stress by predation in the subterranean rodent C. talarum. We found that when tuco-tucos encountered predator cues-fur odor, and largely, immobilization-they responded physiologically by secreting cortisol. This response was accompanied by an associated behavioral response. However, when the increase in plasma cortisol originated exogenously by the injection of cortisol, a behavioral response was not observed. Finally, inhibition of glucocorticoids' synthesis was effective in weakening the behavioral effects produced by immobilization. In conclusion, in tuco-tucos, predator cues act as stress factors that trigger differential increases in plasma cortisol and a behavioral response associated with the appearance of anxiety states.
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Ansiedad/fisiopatología , Conducta Animal/fisiología , Miedo/fisiología , Glucocorticoides/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Conducta Predatoria/fisiología , Roedores/fisiología , Animales , Masculino , Sistema Hipófiso-Suprarrenal/fisiología , Roedores/metabolismoRESUMEN
Background: The hypothalamic-pituitary-adrenal (HPA) axis undergoes adaptations throughout housing system that mightcontribute to the avoidance of adverse effects of welfare status in dogs housed in a shelter. Nevertheless, the influence ofhousing systems and stabling time on glucose and PCV changes is little known. The purpose of the present study was toevaluate the patterns of cortisol, glucose and PCV in dogs housed in a kennel and normal environments, evaluating thedifferences between housing systems, by taking into account the different stabling time and sex.Materials, Methods & Results: The study comprised 98 cross-breed dogs, aged 4 ± 1.5 years, lodged in a kennel (observational group I: N=61, 29 females and 27 males), in paired household dogs (control group II: N=25, 13 females and 12males) and in unpaired household dogs (control group III: N=12, 6 females and 6 males). Females of both groups werespayed. The subjects were studied on the basis of different stabling times, ranged among <1 year, 2 years and 4 years, anddifferent sex.Discussion: This observational study showed that kennelled males lodged for 2 (P < 0.01) and 4 (P < 0.001) years showedlower cortisol concentrations than males lodged <1 year; males lodged for <1 year (P < 0.001) showed higher cortisol concentrations than females; males lodged for 4 year showed lower cortisol concentrations (P < 0.01) than females. Kennelledfemales lodged for 4 year showed higher PCV values (P < 0.001) than females lodged for <1 year. Paired and unpairedhousehold females and males lodged for 4 years showed lower cortisol concentrations (P < 0.01) than 2 years and <1 year.Paired and unpaired household females and males lodged for short-, medium- and long-term times showed higher glucoseconcentrations (P < 0.001) than kennelled dogs. This study showed significant changes of circulating cortisol, glucoseand PCV...(AU)
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Animales , Perros , Sistema Hipófiso-Suprarrenal/fisiología , Sistema Hipotálamo-Hipofisario/fisiología , Hidrocortisona , Glucosa , Hematócrito , Vivienda para Animales , Bienestar del AnimalRESUMEN
The metabolic and hormonal consequences of high-intensity functional training regimens such as CrossFit® (CF) are unclear. Little is known about the triggers and clinical and biochemical features of CF-related overtraining syndrome (OTS). The EROS study compared endocrine and metabolic responses, and eating, social, psychological and body characteristics of OTS-affected (OTS) and healthy athletes (ATL), and non-physically active controls (NPAC). The current study is a post-hoc analysis of the CF subgroups of the EROS study, to evaluate specific characteristics of CF in ATL and OTS. Parameters were overall and pairwise compared among OTS-affected (CF-OTS) and healthy (CF-ATL) athletes that exclusively practiced CF, and NPAC. CF-ATL yielded earlier and enhanced cortisol, GH, and prolactin responses to an insulin tolerance test (ITT), increased neutrophils, lower lactate, increased testosterone, improved sleep quality, better psychological performance, increased measured-to-predicted basal metabolic rate (BMR) ratio and fat oxidation, and better hydration, when compared to NPAC. Conversely, more than 90% of the adaptive changes in CF were lost under OTS, including an attenuation of the hormonal responses to an ITT, increased estradiol, decreased testosterone, and decreased BMR and fat oxidation; the most remarkable trigger of OTS among "HIFT athletes" was the long-term low carbohydrate and calorie intake.
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Trastornos de Traumas Acumulados/etiología , Trastornos de Traumas Acumulados/metabolismo , Acondicionamiento Físico Humano/efectos adversos , Acondicionamiento Físico Humano/métodos , Adolescente , Adulto , Afecto/fisiología , Biomarcadores/metabolismo , Fenómenos Biomecánicos , Catecolaminas/orina , Trastornos de Traumas Acumulados/fisiopatología , Técnicas de Diagnóstico Endocrino , Estradiol/sangre , Hormona de Crecimiento Humana/sangre , Humanos , Hidrocortisona/análisis , Hidrocortisona/sangre , Sistema Hipotálamo-Hipofisario/fisiología , Insulina/sangre , Ácido Láctico/sangre , Masculino , Persona de Mediana Edad , Sistema Hipófiso-Suprarrenal/fisiología , Prolactina/sangre , Saliva/química , Sueño/fisiología , Testosterona/sangre , Adulto JovenRESUMEN
In multiple sclerosis (MS), hypothalamic-pituitary-adrenal (HPA) axis functioning may be dysregulated due to the high cortisol levels involved in the disease activity. HPA axis dysregulation can affect cognitive performance, including executive functions. This study aimed to evaluate hair cortisol concentration and perceived stress as well as verify the association with the performance of executive function in both individuals diagnosed with MS and control individuals. Hair cortisol concentration and perceived stress were evaluated and their association with the performance of healthy individuals (n = 33) and those with MS (n = 64), most of them with remitting-relapsing multiple sclerosis (RRMS) assessed using the Expanded Disability Status Scale (EDSS). Instruments that were employed to measure perceived stress and health aspects included the Behavioral Assessment Dysexecutive Syndrome, Wisconsin Card Sorting Test, Stroop Test, and Perceived Stress Scale. No significant statistical difference was found in the comparison of means among the groups; however, an association was found when using statistical correlation tests between cortisol and cognitive performance in the clinical group (r = 0.31, p = 0.10). Further, an absence of correlations with perceived stress measure was noted. It was possible to observe interaction between group factors and low level of cortisol and problem-solving/cognitive flexibility in the MS group. The results indicated that stress measures used in the present study seem to influence the performance of inhibitory control and problem-solving/cognitive flexibility, the latter with low levels of cortisol in individuals with MS. We suggest studies that examine different measures of physiological stress and characteristics of the disease such as more time of stress.
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Función Ejecutiva/fisiología , Esclerosis Múltiple/fisiopatología , Estrés Fisiológico/fisiología , Adulto , Femenino , Cabello/química , Humanos , Hidrocortisona/análisis , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Masculino , Persona de Mediana EdadRESUMEN
Evidence suggests that natural and adaptive immune responses can trigger neuroendocrine responses. Here, we discuss changes in the activity of the hypothalamus-pituitary-adrenal axis and in autonomic nerves, predominantly of the sympathetic nervous system, in a mouse model of acute infection with Trypanosoma cruzi. The endocrine response includes a marked increased release of glucocorticoid and a decrease of immune-stimulatory hormones, such as dehydroepiandrosterone sulfate, prolactin, and growth hormone during infection. These endocrine changes result in reduced proinflammatory cytokine production, increased regulatory/effector T cell ratio, and thymus atrophy. The sympathetic activity in the spleen of infected mice is also markedly reduced. However, the residual sympathetic activity can modulate the immune response to the parasite, as shown by increased mortality and production of proinflammatory cytokines in sympathetically denervated, infected mice. The outcome of the neuroendocrine response is the moderation of the intensity of the immune response to the parasite, an effect that results in delayed mortality in susceptible mice, and favors the course toward chronicity in more resistant animals.
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Enfermedad de Chagas/inmunología , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal/fisiología , Sistema Nervioso Simpático/fisiología , Trypanosoma cruzi/inmunología , Animales , Linfocitos T CD8-positivos/inmunología , Enfermedad de Chagas/parasitología , Citocinas/metabolismo , Deshidroepiandrosterona/metabolismo , Modelos Animales de Enfermedad , Glucocorticoides/inmunología , Hormona del Crecimiento/metabolismo , Ratones , Neurotransmisores/inmunología , Prolactina/metabolismo , Linfocitos T Reguladores/inmunologíaRESUMEN
In teleost fish, stress initiates a hormone cascade along the hypothalamus-pituitary-interrenal (HPI) axis to provoke several physiological reactions in order to maintain homeostasis. In aquaculture, a number of factors induce stress in fish, such as handling and transport, and in order to reduce the consequences of this, the use of anesthetics has been an interesting alternative. Essential oil (EO) of Lippia alba is considered to be a good anesthetic; however, its distinct chemotypes have different side effects. Therefore, the present study aimed to investigate, in detail, the expression of genes involved with the HPI axis and the effects of anesthesia with the EOs of two chemotypes of L. alba (citral EO-C and linalool EO-L) on this expression in silver catfish, Rhamdia quelen. Anesthesia with the EO-C is stressful for silver catfish because there was an upregulation of the genes directly related to stress: slc6a2, crh, hsd20b, hspa12a, and hsp90. In this study, it was also possible to observe the importance of the hsd11b2 gene in the response to stress by handling. The use of EO-C as anesthetics for fish is not recommended, but, the use of OE-L is indicated for silver catfish as it does not cause major changes in the HPI axis.
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Bagres/fisiología , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Lippia/química , Monoterpenos/farmacología , Aceites de Plantas/farmacología , Monoterpenos Acíclicos , Anestesia/veterinaria , Anestésicos/química , Anestésicos/farmacología , Animales , Sistema Hipotálamo-Hipofisario/fisiología , Monoterpenos/química , Aceites Volátiles/farmacología , Aceites de Plantas/químicaRESUMEN
Background: The hypothalamic-pituitary-adrenal (HPA) axis undergoes adaptations throughout housing system that mightcontribute to the avoidance of adverse effects of welfare status in dogs housed in a shelter. Nevertheless, the influence ofhousing systems and stabling time on glucose and PCV changes is little known. The purpose of the present study was toevaluate the patterns of cortisol, glucose and PCV in dogs housed in a kennel and normal environments, evaluating thedifferences between housing systems, by taking into account the different stabling time and sex.Materials, Methods & Results: The study comprised 98 cross-breed dogs, aged 4 ± 1.5 years, lodged in a kennel (observational group I: N=61, 29 females and 27 males), in paired household dogs (control group II: N=25, 13 females and 12males) and in unpaired household dogs (control group III: N=12, 6 females and 6 males). Females of both groups werespayed. The subjects were studied on the basis of different stabling times, ranged among <1 year, 2 years and 4 years, anddifferent sex.Discussion: This observational study showed that kennelled males lodged for 2 (P < 0.01) and 4 (P < 0.001) years showedlower cortisol concentrations than males lodged <1 year; males lodged for <1 year (P < 0.001) showed higher cortisol concentrations than females; males lodged for 4 year showed lower cortisol concentrations (P < 0.01) than females. Kennelledfemales lodged for 4 year showed higher PCV values (P < 0.001) than females lodged for <1 year. Paired and unpairedhousehold females and males lodged for 4 years showed lower cortisol concentrations (P < 0.01) than 2 years and <1 year.Paired and unpaired household females and males lodged for short-, medium- and long-term times showed higher glucoseconcentrations (P < 0.001) than kennelled dogs. This study showed significant changes of circulating cortisol, glucoseand PCV...