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1.
Am J Hum Biol ; 36(10): e24133, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39034658

RESUMO

Pubertal research has primarily focused on hypothalamic-pituitary-gonadal axis (HPG) regulation of puberty, though the hypothalamic-pituitary-adrenal axis (HPA) is increasingly considered critical. Heightened HPA function proxied by increasing cortisol levels may play a role in accelerated pubertal timing. However, the extent to which cortisol varies across ages and its relation to pubertal changes in linear growth are less well substantiated. We explored relationships between age, linear growth, adiposity, C-peptide (proxy for insulin), and cortisol across puberty, and we tested whether higher cortisol levels are associated with earlier ages at menarche and peak height velocity. We utilize longitudinal data (n = 777 urine samples) from Qom females ages 7-14 (n = 46) and test our pre-registered analysis using Bayesian longitudinal mixed effects models and joint modeling techniques. We find limited evidence supporting the overarching hypothesis that HPA upregulation is associated with pubertal maturation or timing. We find some evidence that HPA upregulation, as proxied by cortisol, may be more clearly related to differences in relative linear growth at early-mid puberty, as measured by height-for-age z-scores. Transdisciplinary perspectives on puberty, including the assumption that stressors acting via cortisol accelerate pubertal development, are discussed.


Assuntos
Hidrocortisona , Puberdade , Humanos , Feminino , Hidrocortisona/metabolismo , Adolescente , Criança , Estudos Longitudinais , Puberdade/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento
2.
J Sci Food Agric ; 104(12): 7454-7463, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38717324

RESUMO

BACKGROUND: The widespread use of sodium propionate as a preservative in food may affect public health. We aimed to assess the effects of sodium propionate on circadian rhythms and pancreatic development in zebrafish and the possible underlying mechanisms. RESULTS: In this experiment, we analyzed the relationship between circadian rhythms and pancreatic development and then revealed the role of the thyroid endocrine system in zebrafish. The results showed that sodium propionate interfered with the rhythmic behavior of zebrafish, and altered the expression of important rhythmic genes. Experimental data revealed that pancreatic morphology and developmental genes were altered after sodium propionate exposure. Additionally, thyroid hormone levels and key gene expression associated with the hypothalamic-pituitary-thyroid axis were significantly altered. Melatonin at a concentration of 1 µmol L-1, with a mild effect on zebrafish, observably alleviated sodium propionate-induced disturbances in circadian rhythms and pancreatic development, as well as regulating the thyroid system. CONCLUSION: Melatonin, while modulating the thyroid system, significantly alleviates sodium propionate-induced circadian rhythm disturbances and pancreatic developmental disorders. We further revealed the deleterious effects of sodium propionate as well as the potential therapeutic effects of melatonin on circadian rhythm, pancreatic development and the thyroid system. © 2024 Society of Chemical Industry.


Assuntos
Ritmo Circadiano , Sistema Hipotálamo-Hipofisário , Melatonina , Pâncreas , Propionatos , Glândula Tireoide , Peixe-Zebra , Animais , Melatonina/farmacologia , Peixe-Zebra/crescimento & desenvolvimento , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Hormônios Tireóideos/metabolismo
3.
Sci Rep ; 11(1): 22527, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795321

RESUMO

In utero heat stress alters postnatal physiological and behavioral stress responses in pigs. However, the mechanisms underlying these alterations have not been determined. The study objective was to characterize the postnatal hypothalamic-pituitary-adrenal axis response of in utero heat-stressed pigs. Pigs were subjected to a dexamethasone suppression test followed by a corticotrophin releasing hormone challenge at 10 and 15 weeks of age. Following the challenge, hypothalamic, pituitary, and adrenal tissues were collected from all pigs for mRNA abundance analyses. At 10 weeks of age, in utero heat-stressed pigs had a reduced (P < 0.05) cortisol response to the corticotrophin releasing hormone challenge versus controls. Additionally, the cortisol response tended to be greater overall (P < 0.10) in 15 versus 10-week-old pigs in response to the dexamethasone suppression test. The cortisol response tended to be reduced overall (P < 0.10) in 15 versus 10-week-old pigs in response to the corticotrophin releasing hormone challenge. Hypothalamic corticotropin releasing hormone mRNA abundance tended to be greater (P < 0.10) in in utero heat-stressed versus control pigs at 15-weeks of age. In summary, in utero heat stress altered some aspects of the hypothalamic-pituitary-adrenal axis related to corticotropin releasing hormone signaling, and age influenced this response.


Assuntos
Hormônio Liberador da Corticotropina/metabolismo , Resposta ao Choque Térmico , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/crescimento & desenvolvimento , Sistema Hipófise-Suprarrenal/fisiologia , Animais , Dexametasona/farmacologia , Feminino , Hidrocortisona/metabolismo , Hipotálamo/metabolismo , Inflamação , Masculino , Neurofisiologia , RNA Mensageiro/metabolismo , Suínos , Fatores de Tempo
4.
Genes (Basel) ; 12(6)2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198905

RESUMO

Kallmann syndrome (KS) is a combination of isolated hypogonadotropic hypogonadism (IHH) with olfactory dysfunction, representing a heterogeneous disorder with a broad phenotypic spectrum. The genetic background of KS has not yet been fully established. This study was conducted on 46 Polish KS subjects (41 males, 5 females; average age: 29 years old). The studied KS patients were screened for defects in a 38-gene panel with next-generation sequencing (NGS) technology. The analysis revealed 27 pathogenic and likely pathogenic (P/LP) variants, and 21 variants of uncertain significance (VUS). The P/LP variants were detected in 20 patients (43.5%). The prevalence of oligogenic P/LP defects in selected genes among KS patients was 26% (12/46), whereas the co-occurrence of other variants was detected in 43% (20 probands). The examined KS patients showed substantial genotypic and phenotypic variability. A marked difference in non-reproductive phenotypes, involving defects in genes responsible for GnRH neuron development/migration and genes contributing to pituitary development and signaling, was observed. A comprehensive gene panel for IHH testing enabled the detection of clinically relevant variants in the majority of KS patients, which makes targeted NGS an effective molecular tool. The significance of oligogenicity and the high incidence of alterations in selected genes should be further elucidated.


Assuntos
Sistema Hipotálamo-Hipofisário/metabolismo , Síndrome de Kallmann/genética , Mutação , Neurogênese , Fenótipo , Adolescente , Adulto , Movimento Celular , Feminino , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/citologia , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Síndrome de Kallmann/metabolismo , Síndrome de Kallmann/patologia , Masculino , Pessoa de Meia-Idade , Neurônios/citologia , Neurônios/metabolismo , Neurônios/fisiologia , Transdução de Sinais
5.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33649816

RESUMO

Di (2­ethylhexyl) phthalate (DEHP), an environmental pollutant, is widely used as a plasticizer and causes serious pollution in the ecological environment. As previously reported, exposure to DEHP may cause thyroid dysfunction of the hypothalamic­pituitary­thyroid (HPT) axis. However, the underlying role of DEHP remains to be elucidated. The present study performed intragastrical administration of DEHP (150, 300 and 600 mg/kg) once a day for 90 consecutive days. DEHP­stimulated oxidative stress increased the thyroid follicular cavity diameter and caused thyrocyte oedema. Furthermore, DEHP exposure altered mRNA and protein levels. Thus, DEHP may perturb TH homeostasis by affecting biosynthesis, biotransformation, bio­transportation, receptor levels and metabolism through disruption of the HPT axis and activation of the thyroid­stimulating hormone (TSH)/TSH receptor signaling pathway. These results identified the formerly unappreciated endocrine­disrupting activities of phthalates and the molecular mechanisms of DEHP­induced thyrotoxicity.


Assuntos
Dietilexilftalato/toxicidade , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Animais , Poluentes Ambientais/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Plastificantes/toxicidade , Ratos Wistar , Receptores da Tireotropina/genética , Receptores da Tireotropina/metabolismo , Receptores do Hormônio Liberador da Tireotropina/genética , Receptores do Hormônio Liberador da Tireotropina/metabolismo , Glândula Tireoide/crescimento & desenvolvimento , Glândula Tireoide/metabolismo , Hormônios Tireóideos/sangue , Hormônios Tireóideos/metabolismo , Fator Nuclear 1 de Tireoide/genética , Fator Nuclear 1 de Tireoide/metabolismo , Tireotropina Subunidade beta/genética , Tireotropina Subunidade beta/metabolismo
6.
Mol Cell Endocrinol ; 524: 111143, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33385474

RESUMO

In this review article, topics of the embryonic origin of the adenohypophysis and hypothalamus and the development of the hypothalamo-hypophyseal system for the completion of metamorphosis in amphibians are included. The primordium of the adenohypophysis as well as the primordium of the hypothalamus in amphibians is of neural origin as shown in other vertebrates, and both are closely associated with each other at the earliest stage of development. Metamorphosis progresses via the interaction of thyroid hormone and adrenal corticosteroids, of which secretion is enhanced by thyrotropin and corticotropin, respectively. However, unlike in mammals, the hypothalamic releasing factor for thyrotropin is not thyrotropin-releasing hormone (TRH), but corticotropin-releasing factor (CRF) and the major releasing factor for corticotropin is arginine vasotocin (AVT). Prolactin, the release of which is profoundly enhanced by TRH at the metamorphic climax, is another pituitary hormone involved in metamorphosis. Prolactin has a dual role: modulation of the metamorphic speed and the development of organs for adult life. The secretory activities of the pituitary cells containing the three above-mentioned pituitary hormones are elevated toward the metamorphic climax in parallel with the activities of the CRF, AVT, and TRH neurons.


Assuntos
Anfíbios/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Metamorfose Biológica , Animais , Diferenciação Celular , Sistema Endócrino/metabolismo , Larva/crescimento & desenvolvimento
7.
Int J Dev Biol ; 65(4-5-6): 207-214, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32930379

RESUMO

Fish present remarkable malleability regarding gonadal sex fate. This phenotypic plasticity enables an organism to adapt to changes in the environment by responding with different phenotypes. The gonad and the brain present this extraordinary plasticity. These organs are involved in the response to environmental stressors to direct gonadal fate, inducing sex change or sex reversal in hermaphroditic and gonochoristic fish, respectively. The presence of such molecular and endocrine plasticity gives this group a large repertoire of possibilities against a continuously changing environment, resulting in the highest radiation of reproduction strategies described in vertebrates. In this review, we provide a broad and comparative view of tremendous radiation of sex determination mechanisms to direct gonadal fate. New results have established that the driving mechanism involves early response to environmental stressors by the brain plus high plasticity of gonadal differentiation and androgens as by-products of stress inactivation. In addition to the stress axis, two other major axes - the hypothalamic-pituitary-gonadal axis and the hypothalamic-pituitary-thyroid axis, which are well known for their participation in the regulation of reproduction - have been proposed to reinforce brain-gonadal interrelationships in the fate of the gonad.


Assuntos
Encéfalo , Peixes , Gônadas , Diferenciação Sexual , Animais , Encéfalo/crescimento & desenvolvimento , Peixes/crescimento & desenvolvimento , Gônadas/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Reprodução
8.
Neuroendocrinology ; 111(5): 421-441, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32365351

RESUMO

INTRODUCTION: Gonadotropin-releasing hormone (GnRH) deficiency causes hypogonadotropic hypogonadism (HH), a rare genetic disorder that impairs sexual reproduction. HH can be due to defective GnRH-secreting neuron development or function and may be associated with other clinical signs in overlapping genetic syndromes. With most of the cases being idiopathic, genetics underlying HH is still largely unknown. OBJECTIVE: To assess the contribution of mutated Semaphorin 3G (SEMA3G) in the onset of a syndromic form of HH, characterized by intellectual disability and facial dysmorphic features. METHOD: By combining homozygosity mapping with exome sequencing, we identified a novel variant in the SEMA3G gene. We then applied mouse as a model organism to examine SEMA3Gexpression and its functional requirement in vivo. Further, we applied homology modelling in silico and cell culture assays in vitro to validate the pathogenicity of the identified gene variant. RESULTS: We found that (i) SEMA3G is expressed along the migratory route of GnRH neurons and in the developing pituitary, (ii) SEMA3G affects GnRH neuron development, but is redundant in the adult hypothalamic-pituitary-gonadal axis, and (iii) mutated SEMA3G alters binding properties in silico and in vitro to its PlexinA receptors and attenuates its effect on the migration of immortalized GnRH neurons. CONCLUSION: In silico, in vitro, and in vivo models revealed that SEMA3G regulates GnRH neuron migration and that its mutation affecting receptor selectivity may be responsible for the HH-related defects.


Assuntos
Hormônio Liberador de Gonadotropina/deficiência , Hipogonadismo/genética , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/metabolismo , Semaforinas/fisiologia , Animais , Células Cultivadas , Consanguinidade , Anormalidades Craniofaciais/etiologia , Deficiências do Desenvolvimento/etiologia , Homozigoto , Humanos , Hipogonadismo/complicações , Deficiência Intelectual/etiologia , Masculino , Camundongos , Linhagem , Irmãos , Síndrome
9.
J Endocrinol ; 248(1): R1-R17, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33112814

RESUMO

Normal function of the hypothalamic-pituitary-adrenal (HPA) axis is critical for survival, and its development is choreographed for age-, sex- and context-specific actions. The liver influences HPA ontogeny, integrating diverse endocrine signals that inhibit or activate its development. This review examines how developmental changes in the expression of genes in the liver coordinate postnatal changes in multiple endocrine systems that facilitate the maturation and sexual dimorphism of the rat HPA axis. Specifically, it examines how the ontogeny of testicular androgen production, somatostatin-growth hormone activities, and hypothalamic-pituitary-thyroid axis activity intersect to influence the hepatic gene expression of insulin-like growth factor 1, corticosteroid-binding globulin, thyroxine-binding globulin, 11ß-hydroxysteroid dehydrogenase type 1 and 5α-reductase type 1. The timing of such molecular changes vary between mammalian species, but they are evolutionarily conserved and are poised to control homeostasis broadly, especially during adversity. Importantly, with the liver as their nexus, these diverse endocrine systems establish the fundamental organization of the HPA axis throughout postnatal development, and thereby ultimately determine the actions of glucocorticoids during adulthood.


Assuntos
Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Fígado/metabolismo , Caracteres Sexuais , Androgênios/metabolismo , Animais , Ratos , Glândula Tireoide/crescimento & desenvolvimento , Hormônios Tireóideos/metabolismo , Transcortina/metabolismo
10.
Placenta ; 104: 179-187, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33360746

RESUMO

INTRODUCTION: Prenatal stress is known to influence fetal hypothalamic-pituitary-adrenal axis (HPA axis) development. Placental 11ß-hydroxysteroid dehydrogenase type 2 (HSD11B2) is a central gene in this pathway, but little is known about what influences its functioning. We assess how maternal distress influences HSD11B2 functioning, and how HSD11B2 in turn, is associated with infant HPA axis development. METHODS: Data come from 24 mother-infant dyads on the Galápagos Islands. Using adjusted linear regression models, we assess the effects of maternal psychosocial (stress and depressive symptoms, measured by the Perceived Stress Scale and the Patient Health Questionnaire-8, respectively) and physiological (HPA axis dysregulation) distress during pregnancy on HSD11B2 methylation and expression and then test how these HSD11B2 measures influence infant HPA axis development. RESULTS: Maternal HPA axis dysregulation during pregnancy is associated with lower placental HSD11B2 expression, which is associated with an exaggerated cortisol reactivity in infants. Sex-specific analyses revealed that maternal depressive symptoms may influence the functioning of placental HSD11B2 differently in girls (n = 11, 46%) than in boys (n = 13, 54%), though the sample size was small. DISCUSSION: These results support a disrupted adaptive framework, in which the ability to upregulate HSD11B2 expression in response to acute stress diminishes as maternal stress becomes chronic. In this model, chronic stress may exhaust the protective mechanism of HSD11B2, leaving the infant vulnerable to high levels of maternal cortisol, which could injure the fetal HPA axis and disrupt long-term neurobehavioral and metabolic development. While larger studies will be needed to confirm these findings, this study offers exploratory results on the effects of maternal distress on both HSD11B2 methylation and expression and the effect of HSD11B2 on offspring HPA axis development.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipófise-Suprarrenal/crescimento & desenvolvimento , Placenta/metabolismo , Estresse Psicológico/metabolismo , Adolescente , Adulto , Metilação de DNA , Feminino , Humanos , Hidrocortisona/análise , Sistema Hipotálamo-Hipofisário/metabolismo , Lactente , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Saliva/química , Adulto Jovem
11.
Biomolecules ; 10(9)2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32917043

RESUMO

Vitamin K (VK) is a fat-soluble vitamin that vertebrates have to acquire from the diet, since they are not able to de novo synthesize it. VK has been historically known to be required for the control of blood coagulation, and more recently, bone development and homeostasis. Our understanding of the VK metabolism and the VK-related molecular pathways has been also increased, and the two main VK-related pathways-the pregnane X receptor (PXR) transactivation and the co-factor role on the γ-glutamyl carboxylation of the VK dependent proteins-have been thoroughly investigated during the last decades. Although several studies evidenced how VK may have a broader VK biological function than previously thought, including the reproduction, little is known about the specific molecular pathways. In vertebrates, sex differentiation and gametogenesis are tightly regulated processes through a highly complex molecular, cellular and tissue crosstalk. Here, VK metabolism and related pathways, as well as how gametogenesis might be impacted by VK nutritional status, will be reviewed. Critical knowledge gaps and future perspectives on how the different VK-related pathways come into play on vertebrate's reproduction will be identified and proposed. The present review will pave the research progress to warrant a successful reproductive status through VK nutritional interventions as well as towards the establishment of reliable biomarkers for determining proper nutritional VK status in vertebrates.


Assuntos
Peixes/genética , Gametogênese/genética , Gônadas/metabolismo , Reprodução/genética , Vitamina K/metabolismo , Animais , Coagulação Sanguínea/genética , Carbono-Carbono Ligases/genética , Carbono-Carbono Ligases/metabolismo , Peixes/crescimento & desenvolvimento , Peixes/metabolismo , Regulação da Expressão Gênica , Gônadas/citologia , Gônadas/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/citologia , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteogênese/genética , Receptor de Pregnano X/genética , Receptor de Pregnano X/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Diferenciação Sexual , Transdução de Sinais , Vitamina K Epóxido Redutases/genética , Vitamina K Epóxido Redutases/metabolismo
12.
Horm Behav ; 126: 104822, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32730760

RESUMO

Oxytocin is important for postnatal developmental experiences for mothers, infants, and transactions between them. Oxytocin is also implicated in adult affiliative behaviors, including social buffering of stress. There is evidence for connections between early life experience and adult oxytocin system functioning, but effects of early experience on behavioral, endocrine, and neurophysiological outcomes related to adult social buffering are not well explored. We use a limited bedding and nesting (LBN) material paradigm as an environmental disruption of early experiences and assessed central oxytocin systems in brain regions related to hypothalamic-pituitary-adrenal (HPA) axis regulation (paraventricular nucleus of the hypothalamus, amygdala, hippocampus). We also assessed developmentally-appropriate social behaviors and HPA reactivity during social buffering testing in adulthood. LBN litters had larger huddles and more pups visible compared to control litters during the first two weeks of life. LBN also altered the developmental trajectory of oxytocin-expressing cells and oxytocin receptor cells, with increases in oxytocin receptor cells at P15 in LBN pups. By adulthood, LBN females had more and LBN males had fewer oxytocin and oxytocin receptor cells in these areas compared to sex-matched controls. Adult LBN females, but not LBN males, had behavioral changes during social interaction and social buffering testing. The sex-specific effects of early experience on central oxytocin systems and social behavior may contribute to female resilience to early life adversity.


Assuntos
Sistema Hipotálamo-Hipofisário , Comportamento Materno/fisiologia , Ocitocina/metabolismo , Sistema Hipófise-Suprarrenal , Receptores de Ocitocina/metabolismo , Animais , Animais Recém-Nascidos , Comportamento Animal/fisiologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Feminino , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Comportamento de Nidação/fisiologia , Ocitocina/farmacologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Sistema Hipófise-Suprarrenal/crescimento & desenvolvimento , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Ratos Long-Evans , Caracteres Sexuais , Comportamento Social , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Estresse Psicológico/prevenção & controle
13.
Dev Neurosci ; 42(1): 2-11, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32653883

RESUMO

Pain is evolutionarily necessary for survival in that it reduces tissue damage by signaling the body to respond to a harmful stimulus. However, in many circumstances, acute pain becomes chronic, and this is often dysfunctional. Adolescent chronic pain is a growing epidemic with an unknown etiology and limited effective treatment options. Given that the relationship between acute pain and chronic pain is not straightforward, there is a need to better understand the factors that contribute to the chronification of pain. Since early life factors are critical to a variety of outcomes in the developmental and adolescent periods, they pose promise as potential mechanisms that may underlie the transition from acute to chronic pain. This review examines two early life factors: poor diet and adverse childhood experiences (ACEs); they may increase susceptibility to the development of chronic pain following surgical procedures or traumatic brain injury (TBI). Beyond their high prevalence, surgical procedures and TBI are ideal models to prospectively understand mechanisms underlying the transition from acute to chronic pain. Common themes that emerged from the examination of poor diet and ACEs as mechanisms underlying this transition included: prolonged inflammation and microglia activation leading to sensitization of the pain system, and stress-induced alterations to hypothalamic-pituitary-adrenal axis function, where cortisol is likely playing a role in the development of chronic pain. These areas provide promising targets for interventions, the development of diagnostic biomarkers, and suggest that biological treatment strategies should focus on regulating the neuroinflammatory and stress responses in an effort to modulate and prevent the development of chronic pain.


Assuntos
Experiências Adversas da Infância/psicologia , Lesões Encefálicas Traumáticas/fisiopatologia , Dor Crônica/fisiopatologia , Dieta , Adolescente , Lesões Encefálicas Traumáticas/complicações , Dor Crônica/complicações , Humanos , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipófise-Suprarrenal/crescimento & desenvolvimento
14.
Int Rev Neurobiol ; 150: 41-76, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32204834

RESUMO

Adverse experiences during childhood can have long-lasting impacts on physical and mental health. At the heart of most theories of how these effects are transduced into health impacts is the activity of stress-mediating systems, most notably the hypothalamic-pituitary-adrenocortical (HPA) axis. Here we review the anatomy and physiology of the axis, models of stress and development, the development of the axis prenatally through adolescence, the role of experience and sensitive periods in shaping its regulation, the social regulation of the axis at different points in development, and finally conclude with suggestions for future research. We conclude that it is clear that early adversity sculpts the stress system, but we do not understand which dimensions have the most impact and at what points in early development. It is equally clear that secure attachment relationships buffer the developing stress system; however, the mechanisms of social buffering and how these may change with development are not yet clear. Another critical issue that is not understood is when and for whom adversity will result in hypo- vs hyperactivity of stress-mediating systems. These and other issues are important for advancing our understanding of how early adversity "gets under the skin" and shapes human physical and mental health.


Assuntos
Experiências Adversas da Infância , Encéfalo , Desenvolvimento Humano/fisiologia , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário , Relações Interpessoais , Apego ao Objeto , Efeitos Tardios da Exposição Pré-Natal , Estresse Psicológico , Adolescente , Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/anatomia & histologia , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Lactente , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia
15.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31650172

RESUMO

CONTEXT: The hypothalamus-pituitary-adrenal (HPA) axis displays a diurnal rhythm. However, little is known about its development in early life. OBJECTIVE: To describe HPA-axis activity and study possible influencing factors in 1-month-old infants. DESIGN: Observational. SETTING: Amsterdam University Medical Center, location VU University Medical Center (VUMC), and Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam. PARTICIPANTS: Fifty-five mother-infant pairs. INTERVENTIONS: Collection of breast milk and infants' saliva 1 month postpartum for analysis of glucocorticoids (GCs; ie, cortisol and cortisone) using liquid chromatography- tandem mass spectrometry. MAIN OUTCOME MEASURE: GC rhythm in infants' saliva and associations with vulnerability for maternal psychological distress (increased Hospital Anxiety and Depression Scale [HADS] score) or consultation at the Psychiatric Obstetric Pediatric (POP clinic), season at sampling, sex, and breast milk GC rhythmicity analyzed with SigmaPlot 14.0 software (Systat Software, San Jose, CA, USA) and regression analyses. RESULTS: A significant biphasic GC rhythm was detected in infants, with mean peaks [standard error of the mean, SEM] at 6:53 am [1:01] and 18:36 pm [1:49] for cortisol, and at 8:50 am [1:11] and 19:57 pm [1:13] for cortisone. HADS score, POP consultation, season at sampling, and sex were not associated with the infants' GC rhythm. Breast milk cortisol maximum was positively associated with infants' cortisol area-under-the-curve (AUC) increase and maximum. Higher breast milk cortisone AUC increase, AUC ground, and maximum were associated with an earlier maximum in infants. Breast milk and infant GC concentrations were associated between 6:00 am and 9:00 am. CONCLUSIONS: A biphasic GC rhythm, peaking in the morning and evening, was seen in 1-month-old infants at a group level. Breast milk GC parameters might be associated with the infants' GC rhythm, possibly caused by a signaling effect of breast milk GCs, or as an associative effect of increased mother-infant synchrony. These results contribute to an increased understanding of early life HPA-axis development.


Assuntos
Ritmo Circadiano , Glucocorticoides/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Leite Humano/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Saliva/metabolismo , Feminino , Seguimentos , Glucocorticoides/análise , Humanos , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Lactente , Recém-Nascido , Masculino , Mães/psicologia , Sistema Hipófise-Suprarrenal/crescimento & desenvolvimento , Gravidez , Prognóstico , Estresse Psicológico
16.
G3 (Bethesda) ; 10(1): 235-246, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31740454

RESUMO

Despite recent taxonomic diversification in studies linking genotype with phenotype, follow-up studies aimed at understanding the molecular processes of such genotype-phenotype associations remain rare. The age at which an individual reaches sexual maturity is an important fitness trait in many wild species. However, the molecular mechanisms regulating maturation timing processes remain obscure. A recent genome-wide association study in Atlantic salmon (Salmo salar) identified large-effect age-at-maturity-associated chromosomal regions including genes vgll3, akap11 and six6, which have roles in adipogenesis, spermatogenesis and the hypothalamic-pituitary-gonadal (HPG) axis, respectively. Here, we determine expression patterns of these genes during salmon development and their potential molecular partners and pathways. Using Nanostring transcription profiling technology, we show development- and tissue-specific mRNA expression patterns for vgll3, akap11 and six6 Correlated expression levels of vgll3 and akap11, which have adjacent chromosomal location, suggests they may have shared regulation. Further, vgll3 correlating with arhgap6 and yap1, and akap11 with lats1 and yap1 suggests that Vgll3 and Akap11 take part in actin cytoskeleton regulation. Tissue-specific expression results indicate that vgll3 and akap11 paralogs have sex-dependent expression patterns in gonads. Moreover, six6 correlating with slc38a6 and rtn1, and Hippo signaling genes suggests that Six6 could have a broader role in the HPG neuroendrocrine and cell fate commitment regulation, respectively. We conclude that Vgll3, Akap11 and Six6 may influence Atlantic salmon maturation timing via affecting adipogenesis and gametogenesis by regulating cell fate commitment and the HPG axis. These results may help to unravel general molecular mechanisms behind maturation.


Assuntos
Linhagem da Célula , Regulação da Expressão Gênica no Desenvolvimento , Salmo salar/genética , Transcriptoma , Animais , Feminino , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Masculino , Salmo salar/crescimento & desenvolvimento , Desenvolvimento Sexual , Transdução de Sinais
17.
J Neonatal Perinatal Med ; 13(1): 55-61, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31609703

RESUMO

BACKGROUND: Developmental changes in the hypothalamus-pituitary-adrenal (HPA) axis during infancy have been reported in term infants, but those in preterm infants have yet to be elucidated. If developmental changes in the HPA axis of preterm infants are modulated by any factors, it may affect their future health. Few studies have examined the lasting consequences of antenatal glucocorticoids on the development of the HPA axis. METHODS: We measured pre- and post-palivizumab vaccination salivary cortisol values in two conforming periods of three-months intervals during infancy, and compared cortisol values and the response of cortisol secretion between groups with and without antenatal glucocorticoid (AG) therapy. RESULTS: Although the strength of the response of cortisol secretion to palivizumab fell age-dependently (until late infancy) in the Non-AG group, the opposite pattern was exhibited in the AG group. The changes of the delta cortisol values between the 2 groups were significant. CONCLUSIONS: This study suggests that the HPA axis of preterm infants whose mothers receive AG therapy may be upregulated during infancy, possibly leading to long lasting health problems.


Assuntos
Glucocorticoides/uso terapêutico , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Injeções Intramusculares , Sistema Hipófise-Suprarrenal/metabolismo , Estresse Fisiológico/fisiologia , Antivirais/administração & dosagem , Estudos de Casos e Controles , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Lactente , Recém-Nascido Prematuro , Masculino , Palivizumab/administração & dosagem , Sistema Hipófise-Suprarrenal/crescimento & desenvolvimento , Cuidado Pré-Natal , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Saliva/química
18.
J Exp Zool A Ecol Integr Physiol ; 331(10): 521-529, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31545013

RESUMO

Life history theory predicts that physiological and behavioral responsiveness to stress should be delayed in development until the benefits of heightened reactivity outweigh the costs of potentially chronic glucocorticoid levels. Birds often acquire stress-responsiveness at locomotor independence, however, both stress-responsiveness and locomotor ability are delayed in birds with altricial developmental strategies. Parrots (Psittacidae) are extremely altricial, but it is not known whether they also postpone physiological responsiveness to stress until locomotor independence. We quantified individual variation in baseline and stress-induced plasma corticosterone (CORT) concentrations, the main avian glucocorticoid, in wild green-rumped parrotlets (Forpus passerinus) of Venezuela at four stages of nestling development. Parrotlet neonates are very underdeveloped and compete for parental care among extreme sibling size hierarchies, a competitive scenario that might benefit from early hypothalamic-pituitary-adrenal (HPA) functionality. Nestlings that underwent a standardized restraint stress-treatment showed higher average CORT concentrations compared to baseline in all age groups sampled, and exhibited no evidence of age-related changes in the stress response. This is 2 weeks before locomotor independence and earlier than previously documented for altricial species. Results suggest that precocity of HPA function may be advantageous to growth and survivorship in extremely altricial birds.


Assuntos
Corticosterona/sangue , Papagaios/crescimento & desenvolvimento , Glândulas Suprarrenais/crescimento & desenvolvimento , Envelhecimento , Animais , Feminino , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Masculino , Papagaios/fisiologia , Restrição Física , Estresse Fisiológico/fisiologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-30218714

RESUMO

Androgens are a recognized class of endocrine disrupting compounds with the ability to impact reproductive status in aquatic organisms. The current study utilized in vitro exposure of mummichog (Fundulus heteroclitus) testis tissue to either the aromatizable androgen 17α-methyltestosterone (MT) or the non-aromatizable androgen 5α-dihydrotestosterone (DHT) over the course of 24 h to determine if there were differential effects on steroidogenic gene expression. Testis tissue was exposed to androgen concentrations of 10-12 M, 10-9 M and 10-6 M for 6, 12, 18 or 24 h, after which a suite of steroidogenic genes, including steroidogenic acute regulatory protein, 3ß-hydroxysteroid dehydrogenase (3ßhsd) and cytochrome P450 17A1 (cyp17a1), were quantified using real-time polymerase chain reaction. Both androgens affected steroidogenic gene expression, with most alterations occurring at the 24-hour time point. The gene with the highest fold-change, and shortest interval to expression alteration, was 3ßhsd for both androgens. Potential differences between the two model androgens were observed in increased expression of cyp17a1 and 11ß-hydroxysteroid dehydrogenase (11ßhsd), which were only altered after exposure to DHT and in expression levels of cytochrome P450 11A1 (cyp11a1), which was upregulated by MT but not altered by DHT. Results from this study show both androgens interact at the gonadal level of the hypothalamus-pituitary-gonadal axis and may possess some distinct gene expression impacts. These data strengthen the current research initiatives of establishing in vitro test systems that allow toxic potential of untested chemicals to be predicted from molecular perturbations.


Assuntos
Androgênios/toxicidade , Disruptores Endócrinos/toxicidade , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Peixes Listrados/fisiologia , Testículo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , 3-Hidroxiesteroide Desidrogenases/química , 3-Hidroxiesteroide Desidrogenases/genética , 3-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Oceano Atlântico , Di-Hidrotestosterona/toxicidade , Estuários , Proteínas de Peixes/genética , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/metabolismo , Peixes Listrados/crescimento & desenvolvimento , Cinética , Masculino , Metiltestosterona/toxicidade , Novo Brunswick , Especificidade de Órgãos , Fosfoproteínas/metabolismo , Esteroide 17-alfa-Hidroxilase/química , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Testículo/crescimento & desenvolvimento , Testículo/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-30367959

RESUMO

Prenatal alcohol exposure (PAE) is known to cause dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including hyperresponsivity to stressors. Dysregulation of the HPA axis plays a role in vulnerability to stress-related disorders, such as anxiety and depression. Thus, the effects of PAE on HPA function may result in increased vulnerability to the effects of stress and, in turn, lead to the development of stress-related disorders. Indeed, individuals prenatally exposed to alcohol have an increased risk of developing anxiety and depression. However, it is unclear whether hypersecretion of corticosterone (CORT) in response to stress per se is involved with mediating differential effects of stress in PAE and control animals. To investigate the role of CORT in mediating effects of stress in both adult females and males following PAE, adrenalectomy with CORT replacement (ADXR) was utilized to produce similar CORT levels among prenatal treatment groups before exposure to chronic unpredictable stress (CUS). Anxiety-like behavior was evaluated using the open field and elevated plus maze, and depressive-like behavior was examined in the forced swim test. Mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA expression was assessed in the medial prefrontal cortex (mPFC), amygdala, and hippocampal formation. Under the non-CUS condition, PAE alone differentially altered anxiety-like behavior in sham but not ADXR females and males, with females showing decreased anxiety-like behavior but males exhibiting increased anxiety-like behavior compared to their control counterparts. There were no effects of PAE alone on depressive-like in females or males. PAE also decreased GR mRNA expression in the hippocampal formation in females but had no effects on MR or GR mRNA expression in any brain region in males. CUS had differential effects on anxiety- and depressive-like behavior in PAE and control animals, and these effects were sex dependent. Importantly, ADXR unmasked differences between PAE and control animals, demonstrating that CORT may play a differential role in modulating behavior and HPA activity/regulation in PAE and control animals, and may do so in a sex-dependent manner.


Assuntos
Transtornos de Ansiedade/metabolismo , Corticosterona/metabolismo , Transtorno Depressivo/metabolismo , Transtornos do Espectro Alcoólico Fetal/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Animais , Depressores do Sistema Nervoso Central/efeitos adversos , Modelos Animais de Doenças , Etanol/efeitos adversos , Feminino , Transtornos do Espectro Alcoólico Fetal/psicologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/crescimento & desenvolvimento , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Receptores de Glucocorticoides/metabolismo , Caracteres Sexuais , Estresse Psicológico/metabolismo
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