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1.
Gen Comp Endocrinol ; 330: 114141, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36272446

RESUMO

Living in variable and unpredictable environments, organisms face recurrent stressful situations. The endocrine stress response, which includes the secretion of glucocorticoids, helps organisms to cope with these perturbations. Although short-term elevations of glucocorticoid levels are often associated with immediate beneficial consequences for individuals, long-term glucocorticoid elevation can compromise key physiological functions such as immunity. While laboratory works highlighted the immunosuppressive effect of long-term elevated glucocorticoids, it remains largely unknown, especially in wild animals, whether this relationship is modulated by individual and environmental characteristics. In this study, we explored the co-variation between integrated cortisol levels, assessed non-invasively using faecal cortisol metabolites (FCMs), and 12 constitutive indices of innate, inflammatory, and adaptive immune functions, in wild roe deer living in three populations with previously known contrasting environmental conditions. Using longitudinal data on 564 individuals, we further investigated whether age and spatio-temporal variations in the quantity and quality of food resources modulate the relationship between FCMs and immunity. Negative covariation with glucocorticoids was evident only for innate and inflammatory markers of immunity, while adaptive immunity appeared to be positively or not linked to glucocorticoids. In addition, the negative covariations were generally stronger in individuals facing harsh environmental constraints and in old individuals. Therefore, our results highlight the importance of measuring multiple immune markers of immunity in individuals from contrasted environments to unravel the complex relationships between glucocorticoids and immunity in wild animals. Our results also help explain conflicting results found in the literature and could improve our understanding of the link between elevated glucocorticoid levels and disease spread, and its consequences on population dynamics.


Assuntos
Cervos , Animais , Cervos/metabolismo , Animais Selvagens/metabolismo , Glucocorticoides/metabolismo , Hidrocortisona/metabolismo , Imunidade Adaptativa
2.
Psychoneuroendocrinology ; 147: 105954, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36308820

RESUMO

BACKGROUND: Evidence suggests posttraumatic stress disorder (PTSD) involves an interplay between psychological manifestations and biological systems. Biological markers of PTSD could assist in identifying individuals with underlying dysregulation and increased risk; however, accurate and reliable biomarkers are yet to be identified. METHODS: A systematic review following the PRISMA guidelines was conducted. Databases included EMBASE, MEDLINE, and Cochrane Central. Studies from a comprehensive 2015 review (Schmidt et al., 2015) and English language papers published subsequently (between 2014 and May 2022) were included. Forty-eight studies were eligible. RESULTS: Alterations in neuroendocrine and immune markers were most commonly associated with PTSD symptoms. Evidence indicates PTSD symptoms are associated with hypothalamic-pituitary-adrenal axis dysfunction as represented by low basal cortisol, a dysregulated immune system, characterized by an elevated pro-inflammatory state, and metabolic dysfunction. However, a considerable number of studies neglected to measure sex or prior trauma, which have the potential to affect the biological outcomes of posttraumatic stress symptoms. Mixed findings are indicative of the complexity and heterogeneity of PTSD and suggest the relationship between allostatic load, biological markers, and PTSD remain largely undefined. CONCLUSIONS: In addition to prospective research design and long-term follow up, it is imperative future research includes covariates sex, prior trauma, and adverse childhood experiences. Future research should include exploration of biological correlates specific to PTSD symptom domains to determine whether underlying processes differ with symptom expression, in addition to subclinical presentation of posttraumatic stress symptoms, which would allow for greater understanding of biomarkers associated with disorder risk and assist in untangling directionality.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Humanos , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Estudos Prospectivos , Biomarcadores/metabolismo , Hidrocortisona/metabolismo
3.
Mol Cell Endocrinol ; 559: 111798, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36243201

RESUMO

Juvenile rainbow trout (Oncorhynchus mykiss) form dominance hierarchies in which subordinates experience chronic social stress and suppression of food intake. Here we tested the hypothesis that inhibition of food intake reflects increased expression of anorexigenic (appetite inhibiting) signals and decreased expression of orexigenic (appetite stimulating) signals. Trout were confined in pairs for 1 or 4 days, or were confined in pairs for 4 days and then allowed to recover from social interactions for 2 or 4 days; sham fish were handled identically but held alone. Subordinates did not feed during social interaction and had lower food intake than dominants or shams during recovery. In parallel, plasma cortisol (∼18-26x) and liver leptin (lep-a1) transcript abundance (∼10-14x) were elevated in subordinates during social interaction but not recovery, suggesting that these factors contributed to the suppression of food intake. Fish deemed likely to become subordinate based on inhibition of food intake in response to a mild stressor also showed elevated liver lep-a1 transcript abundance (∼5x). The moderate response in these fish coupled with a correlation between liver lep-a1 and cortisol suggest that stress-induced elevation of cortisol increased liver lep-a1 transcript abundance in subordinate trout, contributing to stress-induced suppression of food intake.


Assuntos
Oncorhynchus mykiss , Animais , Oncorhynchus mykiss/metabolismo , Hidrocortisona/metabolismo , Apetite , Estresse Psicológico/metabolismo , Fígado/metabolismo
4.
Fa Yi Xue Za Zhi ; 38(4): 459-467, 2022 Aug 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36426688

RESUMO

OBJECTIVES: To explore the damage effects of chronic restraint stress (CRS) on amygdala cells through the rat CRS model. METHODS: The rat CRS model was established, and the changes in body weight and adrenal mass in control group and CRS group were monitored at 1 d, 7 d, 14 d and 21 d. The behavior changes were evaluated by the percentage of retention time of open arms and open arm entries using the elevated plus maze (EPM). ELISA was used to detect the concentrations of rat's corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol. The changes of expression of glucocorticoid receptor (GR) and glial fibrillary acidic protein (GFAP) in amygdala were determined by immunohistochemistry and Western blotting. Ultrastructure changes of glial cell were observed by transmission electron microscopy. The apoptosis rate of amygdala was measured by flow cytometry. RESULTS: Compared with the control group at the same time points, body weight of CRS 1 d, 7 d, 14 d and 21 d groups increased slowly, but adrenal mass increased significantly; the serum level of CRH, cortisol and ACTH increased significantly at 7 d, 14 d and 21 d respectively; the expression of GR in amygdala was increased while that of GFAP was decreased; EPM test suggested that the percentage of retention time of open arms and open arm entries decreased significantly after 14 d. The CRS group showed different degrees of glial cell damage in amygdala, and the apoptosis rate of glial cell was significantly increased in 21 d group. CONCLUSIONS: This study successfully established a CRS model in rats, and anxiety-like behavioral changes in model rats may be caused by apoptosis of amygdala astrocytes.


Assuntos
Tonsila do Cerebelo , Hidrocortisona , Ratos , Animais , Hidrocortisona/metabolismo , Hidrocortisona/farmacologia , Tonsila do Cerebelo/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Apoptose , Peso Corporal
5.
Endocrinology ; 164(1)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36320101

RESUMO

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors suppress adrenal cortical carcinoma cell proliferation and cortisol production; the relationship between mTOR and aldosterone production has not been examined. METHODS: HAC15 cells were incubated with an mTOR activator and several inhibitors including AZD8055 (AZD) in the presence and absence of angiotensin II (AngII). The expression of rapamycin-sensitive adapter protein of mTOR (Raptor) and rapamycin-insensitive companion of mTOR (Rictor), adaptor proteins of mTOR complex 1 and 2, respectively, were studied in the HAC15 cells and deleted by CRISPR/gRNA. RESULTS: The mTOR inhibitors decreased aldosterone induced by AngII. Inhibition of mTOR by AZD significantly suppressed AngII-induced aldosterone and cortisol formation in a dose-dependent manner, whereas the mTOR activator MHY had no effect. AZD did not alter forskolin-induced aldosterone production showing that it is specific to the AngII signaling pathway. AngII-mediated ERK and mTOR activation were suppressed by AZD, along with a concomitant dose-dependent reduction of AngII-induced steroidogenic enzymes including steroidogenic acute regulatory protein, 3ß-hydroxysteroid dehydrogenase-type 2, CYP17A1, and aldosterone synthase protein. Furthermore, mTOR components ribosomal protein S6 kinase (P70S6K) and protein kinase B phosphorylation levels were decreased by AZD. As mTOR exerts its main effects by forming complexes with adaptor proteins Raptor and Rictor, the roles of these individual complexes were studied. We found an increase in the phosphorylation of Raptor and Rictor by AngII and that their CRISPR/gRNA-mediated knockdown significantly attenuated AngII-induced aldosterone and cortisol production. CONCLUSION: mTOR signaling has a critical role in transducing the AngII signal initiating aldosterone and cortisol synthesis in HAC15 cells and that inhibition of mTOR could be a therapeutic option for conditions associated with excessive renin-angiotensin system-mediated steroid synthesis.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Humanos , Angiotensina II/farmacologia , Angiotensina II/metabolismo , Aldosterona/metabolismo , Hidrocortisona/metabolismo , Sirolimo/farmacologia , RNA Guia , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Serina-Treonina Quinases TOR
6.
J Exp Biol ; 225(21)2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36326068

RESUMO

The maternal match hypothesis predicts that maternal exposure to a stressor may help prepare offspring to cope with the same disturbance in later life. Although there is support for this hypothesis, the signals involved in non-genetic inheritance are unclear. In this study, we tested how adult zebrafish exposure to diel cycles of thermal stress (27-36°C), hypoxia (20-85% dissolved oxygen) or the combined treatment affects maternal and embryonic levels of cortisol and heat shock proteins (HSPs). While parental exposure to the thermal, hypoxic or combined treatment for 2 weeks did not affect whole-body cortisol levels, the combined exposure increased ovarian cortisol levels by 4-fold and reduced embryonic cortisol content by 60%. The combined treatment also elicited 3- and 19-fold increases in embryo transcripts involved in cortisol breakdown (11bhsd2) and export (abcb4), respectively. The thermal stress and combined exposure also elicited marked increases in ovary and embryo hsp70a (20- to 45-fold) and HSP70 (3- to 7-fold), and smaller increases in ovary and embryo hsp90aa and hsp47 (2- to 4-fold) and in embryo HSP90 and HSP47 (2- to 6-fold). In contrast, except for increases in ovary hsp90aa (2-fold) and embryo HSP90 (3-fold), the hypoxia treatment had little effect on HSP expression and transfer. Overall, while the embryonic deposition of HSPs largely paralleled the ovarian cellular stress response, the inverse relationship between ovary and embryo cortisol levels suggests the existence of barriers against cortisol deposition in response to environmental stressors. We conclude that the endocrine and cellular stress responses make stressor-specific and distinct contributions to non-genetic inheritance.


Assuntos
Proteínas de Choque Térmico , Peixe-Zebra , Animais , Feminino , Peixe-Zebra/metabolismo , Hidrocortisona/metabolismo , Proteínas de Choque Térmico HSP70 , Hipóxia , Proteínas de Choque Térmico HSP90
7.
BMC Psychiatry ; 22(1): 689, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348380

RESUMO

OBJECTIVE: Using bipolar disorder (BD) as a control, we explored the possible developmental process of impaired glucose metabolism rhythm. METHODS: In total, 441 subjects (77, 162, 134, 54, and 14 in the pre-diabetes [pre-DM], DM, BD, BD + pre-DM, and BD + DM groups, respectively) and 160 controls were included. All subjects were assessed using the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI). The hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes were measured. RESULTS: Cluster analysis showed that the BD, BD + DM, and DM groups were classified as the 'disease group, the BD + pre-DM group as the 'mixed period group', and the pre-DM group as the 'pre-disease group'. The conscientiousness factor scores of the NEO-FFI in the 'disease group' were higher than the norm but lower than the norm in the 'pre-disease group'. The scores of neurotic factors in the 'pre-disease' and 'mixed period' groups were both significantly higher than that in the 'disease group' (corrected p < 0.001). The incidences of the abnormal HPA axis decreased gradually from the 'pre-disease group' to the 'mixed period group' then to the 'disease group', while those of the HPT axis slightly increased at first and then significantly decreased. The overall prediction rate of the multiple logistic regression model was 92.7%. CONCLUSION: This study suggests that progression of pre-diabetes to DM is a continuous process from local abnormalities to rhythm disorder of glucose metabolism. This understanding can be applied to the whole course management and early intervention of DM and to the future development of optimised treatment based on rhythm regulation. TRIAL REGISTRATION: Clinical trial registration number: ChiCTR1800019064. Name of trial registration: Identify and the optimization of treatment for non-infectious chronic diseases under the "stress-dysrhythmia" theory hypothesis (Registration date: 24/10/2018). The full trial protocol can be accessed at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ).


Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Medicina Psicossomática , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Estado Pré-Diabético/metabolismo , Estudos de Casos e Controles
8.
Artigo em Inglês | MEDLINE | ID: mdl-36429527

RESUMO

Previous studies provided contradictory results regarding the influence of maternal, seasonal, and infant factors on breastmilk cortisol, and its associations with breastmilk composition and infant development. This study aimed to assess breastmilk cortisol levels at the first, third, and sixth months of lactation and evaluate the associations with maternal psychosocial, seasonal, and infant factors, breastmilk composition, and infant anthropometric and psychomotor development and temperament. Cortisol concentrations were assessed by ELISA in 24 h breastmilk samples obtained from 38 healthy mothers. Maternal psychological status was assessed by EPDS and PSS-10 and infant psychomotor development was assessed using the Children's Development Scale (DSR). Breastmilk cortisol was 11.2 ± 6.2, 11.2 ± 4.3, and 12.7 ± 6.2 ng/mL at the first, third, and sixth months of lactation (p > 0.05), respectively. In the spring-summer season, we observed lower and higher levels of cortisol in the first and sixth months of lactation (p ≤ 0.05), respectively, but no other associations were detected regarding maternal or infant characteristics. In the third month of lactation, cortisol was related to breastmilk crude protein (ß = 0.318, 0.007-0.630) and infant BMI z-score before adjustment for infant birthweight and sex (Model 2: ß = 0.359, 0.021-0.697), but no other associations with breastmilk composition, infant development, or temperament were confirmed. Our results indicated that breastmilk cortisol is unrelated to maternal and infant factors and has limited influence on breastmilk crude protein, but not on infant anthropometric and psychomotor development.


Assuntos
Hidrocortisona , Leite Humano , Lactente , Feminino , Criança , Humanos , Leite Humano/metabolismo , Hidrocortisona/metabolismo , Desenvolvimento Infantil , Aleitamento Materno , Lactação
9.
J Transl Med ; 20(1): 500, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329487

RESUMO

Apparent mineralocorticoid excess is an autosomal recessive form of monogenic disease characterized by juvenile resistant low-renin hypertension, marked hypokalemic alkalosis, low aldosterone levels, and high ratios of cortisol to cortisone metabolites. It is caused by defects in the HSD11B2 gene, encoding the enzyme 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), which is primarily involved in the peripheral conversion of cortisol to cortisone. To date, over 50 deleterious HSD11B2 mutations have been identified worldwide. Multiple molecular mechanisms function in the lowering of 11ß-HSD2 activity, including damaging protein stability, lowered affinity for the substrate and cofactor, and disrupting the dimer interface. Genetic polymorphism, environmental factors as well as epigenetic modifications may also offer an implicit explanation for the molecular pathogenesis of AME. A precise diagnosis depends on genetic testing, which allows for early and specific management to avoid the morbidity and mortality from target organ damage. In this review, we provide insights into the molecular genetics of classic and non-classic apparent mineralocorticoid excess and aim to offer a comprehensive overview of this monogenic disease.


Assuntos
Cortisona , Hipertensão , Humanos , Cortisona/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , Hidrocortisona/metabolismo , Biologia Molecular
10.
Int J Mol Sci ; 23(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36232518

RESUMO

Stressors cause activation of the hypothalamic-pituitary-adrenal (HPA) axis and a systemic inflammatory response. As a newly proposed cell death manner in recent years, necroptosis occurs in a variety of tissue damage and inflammation. However, the role of necroptosis in HPA axis activation remains to be elucidated. The aim of this study was to investigate the occurrence of necroptosis and its role in HPA activation in a porcine stress model induced by Escherichia coli lipopolysaccharide (LPS). Several typical stress behaviors like fever, anorexia, shivering and vomiting were observed in piglets after LPS injection. HPA axis was activated as shown by increased plasma cortisol concentration and mRNA expression of pituitary corticotropin-releasing hormone receptor 1 (CRHR1) and adrenal steroidogenic acute regulatory protein (StAR). The mRNA expression of tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 in the hypothalamus, pituitary gland and adrenal gland was elevated by LPS, accompanied by the activation of necroptosis indicated by higher mRNA expression of necroptosis signals including receptor-interacting protein kinase (RIP) 1, RIP3, and phosphorylated mixed-lineage kinase domain-like protein (MLKL). Furthermore, necrostatin-1 (Nec-1), an inhibitor of necroptosis, inhibited necroptosis indicated by decreased mRNA levels of RIP1, RIP3, MLKL, and phosphoglycerate mutase family member 5 (PGAM5) in the hypothalamus, pituitary gland and adrenal gland. Nec-1 also decreased the mRNA expression of TNF-α and IL-ß and inhibited the activation of the HPA axis indicated by lower plasma cortisol concentration and mRNA expression of adrenal type 2 melanocortin receptor (MC2R) and StAR. These findings suggest that necroptosis is present and contributes to HPA axis activation induced by LPS. These findings provide a potential possibility for necroptosis as an intervention target for alleviating HPA axis activation and stress responses.


Assuntos
Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Animais , Hormônio Liberador da Corticotropina/metabolismo , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Necroptose , Fosfoglicerato Mutase/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Proteínas Quinases/metabolismo , RNA Mensageiro/metabolismo , Suínos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
11.
BMC Vet Res ; 18(1): 371, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36253770

RESUMO

BACKGROUND: Abnormal or stereotyped behaviours in dairy cows are common in large-scale indoor farms and are usually accompanied by high physiological stress levels. Feed tossing is an abnormal behaviour commonly seen in cows while being fed, making farm management difficult. However, the reasons behind this behaviour have not been sufficiently reported. The objective of this study was to explore the changes in rumen fermentation, serum indicators, inflammatory conditions and the performance of cows with feed tossing behaviour. Holstein cows with similar lactation stages in the same barn were subjected to behaviour observations two times per day for 21 consecutive days. Ten cows with feed tossing behaviour (FT) and ten cows without abnormal behaviours (CON) were selected for further sampling. Plasma samples, rumen fluid, milk yield data of cows, and an indoor environment temperature-humidity index (THI) were collected. RESULTS: There was no significant difference in average daily milk yield during the observation period between feed-tossing cows (n = 68) and the other cows (n = 112). The number of cows showing FT behaviour had a moderately strong negative linear correlation with the THI of the environment. Compared to the CON cows, the FT cows had higher cortisol, norepinephrine and urea nitrogen levels in plasma, as well as higher plasma levels of inflammatory indicators, including total protein, lactate dehydrogenase, albumin, aspartate aminotransferase levels, and the ratio of aspartate aminotransferase to alanine aminotransferase. The FT cows had no significant variations from the CON cows regarding their rumen fermentation indicators, such as pH, ammonia nitrogen, and volatile fatty acids. In addition, 16S rRNA analysis revealed that there might be no clear association between the diversity and abundance of rumen bacteria and feed tossing behaviour. CONCLUSIONS: Our findings suggested that cows might have suffered from high levels of physiological stress and immune state for a long period when they exhibited FT behaviour. The environmental THI could affect the FT behaviour of cows; as the THI increases, the willingness of cows to throw decreases. This work provided the first evidence that feed tossing might be a response associated with high levels of physiological stress and immune. It also explored our insights into a commonly observed behavioural response to cow welfare traits.


Assuntos
Amônia , Rúmen , Alanina Transaminase , Albuminas/metabolismo , Amônia/análise , Ração Animal/análise , Animais , Aspartato Aminotransferases , Bovinos , Dieta/veterinária , Ácidos Graxos Voláteis/metabolismo , Feminino , Fermentação , Hidrocortisona/metabolismo , Lactato Desidrogenases/metabolismo , Lactação , Leite/química , Nitrogênio/metabolismo , Norepinefrina , RNA Ribossômico 16S , Rúmen/metabolismo , Estresse Fisiológico , Ureia/análise
12.
Aging Clin Exp Res ; 34(11): 2733-2740, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36190660

RESUMO

BACKGROUND: In the aging process, the cumulative exposure to stress with increased cortisol levels is considered to be associated to the senescence itself and its related disorders. AIMS: To evaluate the role of cortisol in elderly subjects, with or without dementia, by the means of the AGICO study. METHODS: The AGICO study enrolled patients from ten Geriatric Units in Italy in 2012-2017 (Study Director Prof Paolo Falaschi, S. Andrea Hospital of Rome). Every subject received a comprehensive geriatric assessment (including the Mini-Mental State Examination, MMSE), the neurological examination (with a computed tomography scan or magnetic resonance imaging of the brain), the assessment of the metabolic syndrome (MetS), the evaluation of the cortisol activity by two consecutive urine collections (diurnal and nocturnal). RESULTS: The MMSE was inversely related to the standardized diurnal and nocturnal urinary cortisol levels (p < 0.025 and p < 0.01, respectively) and the age was positively related (p < 0.01 and p < 0.001, respectively). The ratio between the standardized diurnal and nocturnal urinary cortisol levels was 1.50 ± 1.2 (mean ± standard deviation) and it was not modified by the age or dementia. The standardized diurnal and nocturnal urinary cortisol levels were significantly higher in patients with dementia (MMSE < 24) (p < 0.01). In the analysis of the subgroups with MetS, the highest concentrations of diurnal and nocturnal cortisol were found in patients with both dementia and MetS (p < 0.025 and p < 0.01, respectively). DISCUSSION: The AGICO study showed that the stress response significantly and progressively increases with age. CONCLUSION: The cortisol increase in aging is related to the presence of both dementia and metabolic syndrome.


Assuntos
Demência , Síndrome Metabólica , Humanos , Idoso , Síndrome Metabólica/metabolismo , Hidrocortisona/metabolismo , Envelhecimento/fisiologia , Demência/diagnóstico , Periodicidade
13.
Endocrinology ; 164(1)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36269722

RESUMO

Preimplantation maternal stress, characterized by elevated glucocorticoids (GCs), has been linked to reproductive failures caused by impaired oviduct functionality, which is known to be predominantly regulated by the sex steroids, progesterone (P4) and (17)estradiol (E2). Although steroid receptors share analogous structures and binding preferences, the interaction between GCs and E2/P4 in the oviduct has attracted little attention. Using an air-liquid interface culture model, porcine oviduct epithelial cells were stimulated with single (cortisol, E2, P4) or hormone mixtures (cortisol/E2, cortisol/P4) for 12 hours and 72 hours. Cultures were subsequently assessed for epithelial morphometry, bioelectrical properties, and gene expression responses (steroid hormone signaling, oviductal function, immune response, and apoptosis). Results confirmed the suppressive role of P4 in regulating oviduct epithelium characteristics, which was partially opposed by E2. Besides increasing the ratio of ciliated cells, cortisol antagonized the effect of P4 on epithelial polarity and modified sex steroid-induced changes in transepithelial electrical properties. Both sex steroids affected the glucocorticoid receptor expression, while cortisol downregulated the expression of progesterone receptor. The overall gene expression pattern suggests that sex steroid dominates the cotreatment, but cortisol contributes by altering the gene responses to sex steroids. We conclude that besides its individual action, maternal cortisol interplays with sex steroids at phenotypic and molecular levels in the oviduct epithelium, thereby influencing the microenvironment of gametes and early embryos.


Assuntos
Estradiol , Progesterona , Feminino , Humanos , Suínos , Animais , Progesterona/farmacologia , Progesterona/metabolismo , Estradiol/farmacologia , Estradiol/metabolismo , Hidrocortisona/farmacologia , Hidrocortisona/metabolismo , Epitélio , Oviductos
14.
Rev. clín. esp. (Ed. impr.) ; 222(8): 458-467, oct. 2022.
Artigo em Espanhol | IBECS | ID: ibc-209984

RESUMO

Objetivo Se evaluó la prevalencia de hiperplasia suprarrenal macronodular bilateral primaria (PBMAH). También se analizó el fenotipo diferencial de los pacientes con PBMAH en comparación con otras lesiones suprarrenales bilaterales que no cumplían con la definición de PBMAH. Métodos Revisamos las historias clínicas de 732 pacientes diagnosticados de incidentaloma suprarrenal en nuestro centro. Se incluyeron 98 pacientes con hipercortisolismo subclínico para el análisis. Se definió PBMAH como la presencia de cortisol plasmático > 1,8 μg/dL después de una prueba de 1 mg de dexametasona durante la noche, hiperplasia suprarrenal bilateral y nódulos suprarrenales bilaterales > 1 cm. Resultados Un total de 31 pacientes tenían PBMAH. Los pacientes con PBMAH mostraron una mayor prevalencia de secreción autónoma de cortisol (cortisol plasmático > 5,0 μg/dL después de la prueba de 1 mg de dexametasona durante la noche) que los pacientes sin PBMAH (OR 4,1, IC del 95%: 1,38-12,09, p = 0,010). El tamaño del tumor y la masa adenomatosa total fueron significativamente mayores en pacientes con PBMAH en comparación con los pacientes sin PBMAH (30,2 ± 12,16 vs. 24,3 ± 8,47 mm, p = 0,010 y 53,9 ± 20,8 vs. 43,3 ± 14,62 mm, p = 0,023), respectivamente. Una mayor proporción de pacientes con PBMAH tenían diabetes en comparación con los pacientes sin PBMAH (45,2% vs. 25,4%, p = 0,05). Conclusión PBMAH está presente en un tercio de los pacientes con incidentaloma suprarrenal e hipercortisolismo subclínico. Los pacientes con PBMAH mostraron una mayor secreción autónoma de cortisol, mayor tamaño del tumor y diabetes que aquellos sin PBMAH (AU)


Aim This study evaluated prevalence of primary bilateral macronodular adrenal hyperplasia (PBMAH). It also analyzed the differential phenotype of patients with PBMAH compared to other bilateral adrenal lesions that do not meet the definition of PBMAH. Methods We reviewed the medical records of 732 patients diagnosed with an adrenal incidentaloma at our center. Ninety-eight patients with subclinical hypercortisolism were included in the analysis. We defined PBMAH as the presence of plasma cortisol > 1.8 μg/dL after an over-night 1-mg dexamethasone test, bilateral adrenal hyperplasia, and bilateral adrenal nodules > 1 cm. Results A total of 31 patients had PBMAH. Patients with PBMAH showed greater prevalence of autonomous cortisol secretion (plasma cortisol > 5.0 μg/dL after an overnight 1-mg dexamethasone test) than patients without PBMAH (OR 4.1, 95%CI 1.38-12.09, p = 0.010). Tumor size and total adenomatous mass were significantly greater in patients with PBMAH compared to patients without PBMAH (30.2 ± 12.16 vs. 24.3 ± 8.47 mm, p = 0.010 and 53.9 ± 20.8 vs. 43.3 ± 14.62 mm, p = 0.023), respectively. A greater proportion of patients with PBMAH had diabetes compared to patients without PBMAH (45.2% vs. 25.4%, p = 0.05). Conclusion PBMAH is present in one-third of patients with adrenal incidentaloma and subclinical hypercortisolism. Patients with PBMAH showed greater autonomous cortisol secretion, bigger tumor size, and higher rates of diabetes than those without PBMAH (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias das Glândulas Suprarrenais/diagnóstico , Síndrome de Cushing/diagnóstico , Hidrocortisona/metabolismo , Hiperplasia Suprarrenal Congênita/diagnóstico , Neoplasias das Glândulas Suprarrenais/epidemiologia , Prevalência , Fenótipo , Achados Incidentais
15.
Dev Psychobiol ; 64(7): e22322, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36282747

RESUMO

Parents are theorized to play an important role in helping young children to downregulate arousal to achieve sufficient and good-quality sleep. To my knowledge, however, the links between parenting and children's physiological arousal at bedtime and subsequent nighttime sleep have not been empirically tested. The present study examined 3- to 6-year-old children's evening cortisol levels as a pathway linking parental involvement at bedtime to children's nighttime sleep duration and quality. Fifty-one children (53% male, 47% female; 80% White, 18% Biracial, 2% Black) and their families participated. Parental involvement (presence, contact, quiet activities) was assessed by raters from video recordings of one night of bedtime. Children's evening cortisol levels were measured from saliva samples taken at bedtime by parents across three nights. Children's nighttime sleep (minutes, efficiency) was determined from an actigraph worn the same three nights. Path analyses controlling for child and family demographics provided support for three significant indirect effects: lower child evening cortisol acted as a pathway linking greater parental presence at bedtime to more child nighttime sleep minutes and higher sleep efficiency, and lower child evening cortisol also linked greater parental contact at bedtime to higher sleep efficiency. Among this low-risk sample, the findings suggest that encouraging parental involvement in young children's bedtime routine may promote healthy sleep by way of reduced child physiological arousal.


Assuntos
Hidrocortisona , Sono , Criança , Humanos , Masculino , Feminino , Pré-Escolar , Hidrocortisona/metabolismo , Sono/fisiologia , Pais , Poder Familiar , Nível de Alerta
16.
Endocr Regul ; 56(4): 265-270, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36270344

RESUMO

Objective. This study was aimed to evaluate the prevalence of Cushing's syndrome and the diagnostic performance of the 1 mg dexamethasone suppression test in class 3 obese patients. Methods. Anthropometric measurements and other laboratory data, including 1 mg dexamethasone suppression test of 753 class 3 obese patients, who applied to the Endocrinology and Metabolism Outpatient Clinic for the pre-bariatric surgery evaluation between 2011 and 2020, were evaluated retrospectively. Results. An abnormal response to the 1 mg dexamethasone suppression test (cortisol ≥1.8 mcg/dl) was observed in 24 patients and the presence of Cushing's syndrome was confirmed by additional tests in 6 patients. The prevalence of abnormal dexamethasone suppression test was 3.18% and the prevalence of Cushing's syndrome 0.79%. The specificity value was determined as 97.5% for 1 mg dexamethasone suppression test with cortisol threshold value ≥1.8 mcg/dl. Conclusions. The prevalence of Cushing's syndrome was found to be low in class 3 obese patients and 1 mg of dexamethasone suppression test had a very sufficient performance for Cushing's syndrome screening in this patient group.


Assuntos
Síndrome de Cushing , Humanos , Síndrome de Cushing/diagnóstico , Hidrocortisona/metabolismo , Dexametasona/farmacologia , Estudos Retrospectivos , Obesidade/epidemiologia
17.
Int J Mol Sci ; 23(20)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36293344

RESUMO

The present work aimed to study the role of dietary tryptophan supplementation in modulating the European seabass (Dicentrarchus labrax) immune condition during stressful rearing conditions (i.e., 15 days exposure to high density), as well as the immune response to acute inflammation after intraperitoneal injection of a bacterial pathogen. Stress alone did not compromise seabass health indicators. In contrast, a clear peripheral and local inflammatory response was observed in response to the inoculated bacteria. Moreover, exposure to a high stocking density seemed to exacerbate the inflammatory response at early sampling points, compared to fish stocked at a lower density. In contrast, stressed fish presented some immune-suppressing effects on the T-cell surface glycoprotein receptor expressions at a late sampling point following inflammation. Regarding the effects of dietary tryptophan, no changes were observed on seabass immune indicators prior to inflammation, while a small number of immunosuppressive effects were observed in response to inflammation, supporting tryptophan's role in the promotion of immune-tolerance signals during inflammation. Nonetheless, tryptophan dietary supplementation improved the inflammatory response against a bacterial pathogen during stressful conditions, supported by a reduction of plasma cortisol levels, an up-regulation of several immune-related genes at 48 h, and an inversion of the previously observed, stress-induced T-cell suppression. Finally, the involvement of tryptophan catabolism in macrophages was confirmed by the up-regulation of genes involved in the kynurenine pathway. The present study brings new insights regarding the immune modulatory role of tryptophan during stressful conditions in fish, thus allowing for the development of novel prophylactic protocols during vaccination by intraperitoneal injection in the European seabass.


Assuntos
Bass , Animais , Bass/genética , Triptofano/metabolismo , Ração Animal/análise , Hidrocortisona/metabolismo , Cinurenina/metabolismo , Resistência à Doença , Inflamação , Glicoproteínas de Membrana/metabolismo
18.
Ecotoxicol Environ Saf ; 244: 114050, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36063614

RESUMO

Exposure to ammonia can cause convulsions, coma, and death. In this study, we investigate the effects of ammonia exposure on immunoregulatory and neuroendocrine changes in Takifugu rubripes. Fish were sampled at 0, 12, 24, 48, and 96 h following exposure to different ammonia concentrations (0, 5, 50, 100, and 150 mg/L). Our results showed that exposure to ammonia significantly reduced the concentrations of C3, C4, IgM, and LZM whereas the heat shock protein 70 and 90 levels significantly increased. In addition, the transcription levels of Mn-SOD, CAT, GRx, and GR in the liver were significantly upregulated following exposure to low ammonia concertation, however, downregulated with increased exposure time. These findings suggest that ammonia poisoning causes oxidative damage and suppresses plasma immunity. Ammonia exposure also resulted in the elevation and depletion of the T3 and T4 levels, respectively. Furthermore, ammonia stress induced an increase in the corticotrophin-releasing hormone, adrenocorticotropic hormone, and cortisol levels, and a decrease in dopamine, noradrenaline, and 5-hydroxytryptamine levels in the brain, illustrating that ammonia poisoning can disrupt the endocrine and neurotransmitter systems. Our results provide insights into the mechanisms underlying the neurotoxic effects of ammonia exposure, which helps to assess the ecological and environmental health risks of this contaminant in marine fish.


Assuntos
Amônia , Takifugu , Hormônio Adrenocorticotrópico/metabolismo , Amônia/metabolismo , Animais , Encéfalo/metabolismo , Dopamina/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Hidrocortisona/metabolismo , Imunidade , Imunoglobulina M/metabolismo , Neurotransmissores/metabolismo , Norepinefrina/metabolismo , Serotonina/metabolismo , Superóxido Dismutase/metabolismo , Takifugu/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo
19.
Int J Mol Sci ; 23(18)2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36142817

RESUMO

As lower vertebrates, teleost species could be affected by dynamic aquatic environments and may respond to environmental changes through the hypothalamus-pituitary-gonad (HPG) axis to ensure their normal growth and sexual development. Chinese sea bass (Lateolabrax maculatus), euryhaline marine teleosts, have an extraordinary ability to deal with a wide range of salinity changes, whereas the salinity decrease during their sex-maturation season may interfere with the HPG axis and affect their steroid hormone metabolism, resulting in abnormal reproductive functioning. To this end, in this study, 40 HPG axis genes in the L. maculatus genome were systematically characterized and their copy numbers, phylogenies, gene structures, and expression patterns were investigated, revealing the conservation of the HPG axis among teleost lineages. In addition, freshwater acclimation was carried out with maturing male L. maculatus, and their serum cortisol and 11-ketotestosterone (11-KT) levels were both increased significantly after the salinity change, while their testes were found to be partially degraded. After salinity reduction, the expression of genes involved in cortisol and 11-KT synthesis (cyp17a, hsd3b1, cyp21a, cyp11c, hsd11b2, and hsd17b3) showed generally upregulated expression in the head kidneys and testes, respectively. Moreover, cyp11c and hsd11b2 were involved in the synthesis and metabolism of both cortisol and 11-KT, and after salinity change their putative interaction may contribute to steroid hormone homeostasis. Our results proved the effects of salinity change on the HPG axis and steroidogenic pathway in L. maculatus and revealed the gene interactions involved in the regulation of steroid hormone levels. The coordinated interaction of steroidogenic genes provides comprehensive insights into steroidogenic pathway regulation, as well as sexual development, in teleost species.


Assuntos
Bass , Animais , Bass/genética , Bass/metabolismo , China , Gônadas/metabolismo , Hidrocortisona/metabolismo , Hipotálamo/metabolismo , Masculino , Complexos Multienzimáticos/metabolismo , Salinidade
20.
Theriogenology ; 192: 62-72, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36063671

RESUMO

Oocyte in vitro maturation (IVM) and vitrification procedures lead to detrimental effects on the overall oocyte quality. The addition of antioxidants during IVM, such as the coenzyme Q10 (Q10), has been demonstrated to positively impact on the cumulus-oocyte complexes due to its role in protection from oxidative damage and modulating gene transcription. Furthermore, glucocorticoids (GC) regulate gene transcription, energy metabolism and apoptosis during the early steps of reproduction. In this sense, most GC actions are mediated by the glucocorticoid receptor (NR3C1), a transcription factor. However, the specific roles of GC in ovarian physiology and oocyte maturation are still unknown. In this regard, a better knowledge on the expression of GC-related and apoptosis-related genes during IVM and cryopreservation procedures could potentially benefit the refinement of assisted reproductive techniques in the bovine species. The present study aims to explore the expression of NR3C1 mRNA in fresh and vitrified bovine oocytes and cumulus cells in response to Q10 (50 µM), and the effect of cortisol addition (0.25 µM, 0.5 µM) on the expression of NR3C1. We also studied the mRNA expression of NR3C1-related genes belonging to the GC regulation pathway, such as hydroxysteroid dehydrogenases (HSD11B1; HSD11B2), immunophilins (FKBP4; FKBP5), signal transducers and activators of transcription (STAT3; STAT5A), the mineralocorticoid receptor (NR3C2), and to the apoptosis pathway, such as the anti- (BCL2) and pro-apoptotic (BAX) mRNA transcripts in oocytes and cumulus cells 1) after IVM, and 2) after vitrification, both in presence or absence of Q10 supplementation during IVM. Our results show that there is an increase in the NR3C1 receptor expression after vitrification of oocytes, but not after exogenous cortisol supplementation during IVM. In addition, Q10 reduces the mRNA expression of HSD11B1 and FKBP5 in oocytes at levels of immature oocytes (HSD11B1 mRNA expression also in cumulus cells), and the BAX:BCL2 ratio mRNA expression. After vitrification in the presence of Q10, HSD11B2 mRNA expression increases in cumulus cells, while HSD11B1 and BAX:BCL2 mRNA expression decreases significantly both in oocytes and cumulus cells. In conclusion, our results show for the first time the effect of IVM, vitrification and Q10 supplementation on the mRNA relative expression of GC-related and apoptosis genes, and the effect of vitrification in the protein expression of NR3C1.


Assuntos
Células do Cúmulo , Vitrificação , Animais , Apoptose , Bovinos , Células do Cúmulo/fisiologia , Suplementos Nutricionais , Feminino , Glucocorticoides/metabolismo , Glucocorticoides/farmacologia , Hidrocortisona/metabolismo , Hidroxiesteroide Desidrogenases/metabolismo , Hidroxiesteroide Desidrogenases/farmacologia , Imunofilinas/metabolismo , Imunofilinas/farmacologia , Técnicas de Maturação in Vitro de Oócitos/métodos , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oócitos/fisiologia , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/metabolismo , Fatores de Transcrição/metabolismo , Ubiquinona/análogos & derivados , Proteína X Associada a bcl-2/metabolismo
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