RESUMO
Hormonal contraceptives (HCs) are one of the most highly prescribed classes of drugs in the world used for both contraceptive and noncontraceptive purposes. Despite their prevalent use, the impact of HCs on the brain remains inadequately explored. This review synthesizes recent findings on the neuroscience of HCs, with a focus on human structural neuroimaging as well as translational, nonhuman animal studies investigating the cellular, molecular, and behavioral effects of HCs. Additionally, we consider data linking HCs to mood disorders and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and stress response as a potential mediator. The review also addresses the unique sensitivity of the adolescent brain to HCs, noting significant changes in brain structure and function when HCs are used during this developmental period. Finally, we discuss potential effects of HCs in combination with smoking-derived nicotine on outcomes of ischemic brain damage. Methodological challenges, such as the variability in HC formulations and user-specific factors, are acknowledged, emphasizing the need for precise and individualized research approaches. Overall, this review underscores the necessity for continued interdisciplinary research to elucidate the neurobiological mechanisms of HCs, aiming to optimize their use and improve women's health.
Assuntos
Encéfalo , Humanos , Animais , Feminino , Encéfalo/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Contraceptivos Hormonais/farmacologia , Neurociências/métodos , Anticoncepcionais Orais Hormonais/farmacologiaRESUMO
The hypometabolism induced by fasting has great potential in maintaining health and improving survival in extreme environments, among which thyroid hormone (TH) plays an important role in the adaptation and the formation of new energy metabolism homeostasis during long-term fasting. In the present review, we emphasize the potential of long-term fasting to improve physical health and emergency rescue in extreme environments, introduce the concept and pattern of fasting and its impact on the body's energy metabolism consumption. Prolonged fasting has more application potential in emergency rescue in special environments. The changes of THs caused by fasting, including serum biochemical characteristics, responsiveness of the peripheral and central hypothalamus-pituitary-thyroid (HPT) axis, and differential changes of TH metabolism, are emphasized in particular. It was proposed that the variability between brain and liver tissues in THs uptake, deiodination activation and inactivation is the key regulatory mechanism for the cause of peripheral THs decline and central homeostasis. While hypothalamic tanycytes play a pivotal role in the fine regulation of the HPT negative feedback regulation during long-term fasting. The study progress of tanycytes on thyrotropin-releasing hormone (TRH) release and deiodination is described in detail. In conclusion, the combination of the decrease of TH metabolism in peripheral tissues and stability in the central HPT axis maintains the basal physiological requirement and new energy metabolism homeostasis to adapt to long-term food scarcity. The molecular mechanisms of this localized and differential regulation will be a key research direction for developing measures for hypometabolic applications in extreme environment.
Assuntos
Metabolismo Energético , Jejum , Hormônios Tireóideos , Humanos , Jejum/metabolismo , Jejum/fisiologia , Hormônios Tireóideos/metabolismo , Animais , Metabolismo Energético/fisiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiologia , HomeostaseRESUMO
Foster parents have been shown to report higher levels of parenting stress but also more dyadic coping (DC) behaviors in their partnership than biological parents, which might be an important protective factor that helps them cope with daily stressors. Here, we examined how parenting stress and DC are related in foster and biological parents and whether these are reflected in long-term alterations of hypothalamic-pituitary-adrenocortical (HPA) axis activity. A total of 79 foster mothers and 131 biological mothers participated in a longitudinal study. At the initial assessment, children were aged 2-7 years and lived for an average of 18 months in their current foster family. Mothers' cortisol and dehydroepiandrosterone (DHEA) concentrations and their cortisol/DHEA ratios were assessed in scalp hair twice with approximately 11 months in between, while their perceived parenting stress and DC were measured by self-report questionnaires. Results showed no significant differences between foster mothers and biological mothers in cortisol, DHEA and cortisol/DHEA concentrations. While more DC was longitudinally related to lower levels of parenting stress across both study groups, no significant associations were found to endocrine markers. Thus, these findings indicate that increased parenting stress levels were not, or not strongly, reflected in HPA axis alterations as assessed in hair. Our findings thus add evidence for non-significant associations between self-reported perceived stress and chronic HPA axis markers. Future studies may explore whether early interventions, including those aimed at promoting and maintaining positive DC, are beneficial in preventing the development of stress-related illnesses in foster parents.
Assuntos
Adaptação Psicológica , Desidroepiandrosterona , Hidrocortisona , Mães , Poder Familiar , Estresse Psicológico , Humanos , Feminino , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Mães/psicologia , Hidrocortisona/metabolismo , Hidrocortisona/análise , Adulto , Poder Familiar/psicologia , Criança , Adaptação Psicológica/fisiologia , Pré-Escolar , Desidroepiandrosterona/metabolismo , Estudos Longitudinais , Masculino , Biomarcadores/metabolismo , Resiliência Psicológica , Cabelo/química , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Cuidados no Lar de Adoção/psicologiaRESUMO
Childhood exposure to interparental intimate partner violence (i-IPV) is a pervasive form of child maltreatment, posing major public health concerns and elevating risks for enduring adverse clinical and developmental consequences. However, assessing the full spectrum of clinical effects is challenging, potentially leading to inconsistent identification of children in need of early intervention. This systematic review aimed to identify hypothalamic-pituitary-adrenocortical axis dysfunction following i-IPV exposure, elucidating the underlying biopsychobehavioural mechanisms and predicting adverse outcomes. We searched Embase, MEDLINE, and PsycINFO for peer-reviewed studies from infancy through adolescence, screened reference lists and conducted forward searches. Analysis of 23 publications (N = 1848) revealed associations between i-IPV and altered adrenocortical function from early childhood, influenced by FKBP5 haplotype, parental caregiving and offspring emotional insecurity. Results showed that the adrenocortical stress response may predict internalising and externalising problems, childhood asthma, impaired executive function and poor academic performance. Nonetheless, inconsistencies in findings between studies suggest methodological heterogeneity and potential bias. Identifying biomarkers such as cortisol can enhance prediction and mechanism-based intervention efforts but long-term studies with a common theoretical and methodological framework are needed for comprehensive understanding. Integrating biological, emotional, and behavioural assessments could potentiate trauma services and research, ultimately improving outcomes for affected children.
Assuntos
Violência por Parceiro Íntimo , Humanos , Criança , Adolescente , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Sistema Hipófise-Suprarrenal/metabolismoRESUMO
Chronic pain is a prevalent condition with significant impacts on individuals' lives, including heightened stress and impaired physiological functioning. Given that work and family are the two main social domains where stress manifests, this study aimed to investigate the interactions between chronic pain, work-family stressors, and diurnal cortisol patterns to understand how chronic pain affects daily life and physiological stress responses. We identified 1,413 adults with chronic pain and 1,413 matched controls within MIDUS II samples to examine work-family spillover, daily work and home stressors, and cortisol levels across multiple days. The chronic pain group reported more negative work to family spillover and experienced more instances of stressful home events, particularly avoided arguments. These results align with literature suggesting chronic pain exacerbates tensions in close relationships and increases stress. The chronic pain group also had higher cortisol levels cross late-day periods, indicative of hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This dysregulation is associated with poorer health outcomes, including increased inflammation and psychological distress. We did not find any differences in previously identified cortisol profiles, which are higher-level summaries of cortisol levels within each day. We discuss why such difference might not have appeared in this sample.
Assuntos
Dor Crônica , Ritmo Circadiano , Hidrocortisona , Saliva , Estresse Psicológico , Humanos , Hidrocortisona/metabolismo , Masculino , Feminino , Dor Crônica/fisiopatologia , Dor Crônica/psicologia , Pessoa de Meia-Idade , Ritmo Circadiano/fisiologia , Estresse Psicológico/fisiopatologia , Adulto , Saliva/química , Saliva/metabolismo , Família , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologiaRESUMO
The naked mole-rat (Heterocephalus glaber) is a unique model mammal in which to study socially induced inhibition of the hypothalamic-pituitary-gonadal (HPG) axis. Naked mole-rat groups exhibit a high degree of reproductive bias in which breeding is restricted to one female (the queen) and one male, with subordinate non-breeding colony members rarely, if ever, having the opportunity to reproduce due to a dysfunctional HPG axis. It is posited that aggression directed at subordinates by the queen suppresses reproduction in these subordinates, yet the underlying physiological mechanisms causing this dysfunction are unknown. This study aimed to investigate the possible factors contributing to the dysfunction of the HPG axis in subordinate female naked mole-rats with a specific focus on the role of ovarian feedback and stress-related factors such as circulating glucocorticoid and endogenous opioid peptides. The results showed that stress-related factors appear to not mediate the suppression of reproductive function in subordinate female naked mole rats. Indeed, in some cases, the activation of the stress axis may lead to reproductive activation instead of deactivation. At the same time, the role of ovarian sex steroid feedback in reproductive suppression is likely limited and not clearly delineated. This study highlights the need for detailed studies to elucidate the mechanism of reproductive suppression in this unique model mammalian species which may shed light on, and reveal novel mechanisms, in the social regulation of reproduction.
Assuntos
Glucocorticoides , Sistema Hipotálamo-Hipofisário , Ratos-Toupeira , Animais , Ratos-Toupeira/fisiologia , Feminino , Sistema Hipotálamo-Hipofisário/metabolismo , Glucocorticoides/metabolismo , Peptídeos Opioides/metabolismo , Peptídeos Opioides/fisiologia , Reprodução/fisiologia , Masculino , Ovário/fisiologia , Dominação-Subordinação , Eixo Hipotalâmico-Hipofisário-GonadalRESUMO
BACKGROUND: The mechanisms at the basis of depression are still matter of debate, but several studies in the literature suggest common pathways with dementia (genetic predispositions, metabolic and inflammatory mechanisms, neuropathological changes) and other geriatric syndromes. AIMS: To evaluate the role of cortisol (as marker of the HPA, hypothalamus-pituitary-adrenal axis hyperactivity) in elderly subjects with depressive symptoms (by the means of the AGICO, AGIng and COrtisol, study), in relationship to the presence of the major geriatric syndromes. METHODS: The AGICO study enrolled patients from ten Geriatric Units in Italy. Every subject received a comprehensive geriatric assessment or CGA (including the Mini Mental State Examination or MMSE, Geriatric Depression Scale or GDS and Cornell Scale for Depression in Dementia or CSDD), 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), a CGA-derived frailty index (FI) and a modified measure of allostatic load (AL). RESULTS: The MMSE scores were significantly and inversely related to the values of GDS (p < 0.001) and CSDD (p < 0.05), respectively. The patients with depressive symptoms (GDS/CSDD > 8) showed significantly increased disability, MetS, inflammation, FI and AL and significantly reduced MMSE and renal function. The diurnal and nocturnal urinary cortisol levels in the patients with depressive symptoms (GDS/CSDD > 8) were higher with respects to controls (p < 0.05 for nocturnal difference). DISCUSSION: The AGICO study showed that the stress response is activated in the patients with depression. CONCLUSION: The depression in elderly patient should be reconsidered as a systemic disease, with coexisting major geriatric syndromes (disability, dementia, frailty) and combined pathogenetic mechanisms (metabolic syndrome, impaired renal function, low-grade inflammation, and allostatic load). Cortisol confirmed its role as principal mediator of the aging process in both dementia and metabolic syndrome.
Assuntos
Depressão , Hidrocortisona , Humanos , Hidrocortisona/urina , Idoso , Feminino , Masculino , Depressão/urina , Idoso de 80 Anos ou mais , Avaliação Geriátrica , Demência/urina , Demência/fisiopatologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Síndrome Metabólica/urina , Ritmo Circadiano/fisiologiaRESUMO
Major Depressive Disorder, or depression, has been extensively linked to dysregulated HPA axis function, chronic inflammation and cardiovascular diseases. While the former two have been studied in depth, the mechanistic connection between depression and cardiovascular disease is unclear. As major mediators of vascular homeostasis, vascular pathology and immune activity, endothelial cells represent an important player connecting the diseases. Exaggerated inflammation and glucocorticoid function are important topics to explore in the endothelial response to MDD. Glucocorticoid resistance in several cell types strongly promotes inflammatory signaling and results in worsened severity in many diseases. However, endothelial health and inflammation in chronic stress and depression are rarely considered from the perspective of glucocorticoid signaling and resistance. In this review, we aim to discuss (1) endothelial dysfunction in depression, (2) inflammation in depression, (3) general glucocorticoid resistance in depression and (4) endothelial glucocorticoid resistance in depression co-morbid inflammatory diseases. We will first describe vascular pathology, inflammation and glucocorticoid resistance separately in depression and then describe their potential interactions with one another in depression-relevant diseases. Lastly, we will hypothesize potential mechanisms by which glucocorticoid resistance in endothelial cells may contribute to vascular disease states in depressed people. Overall, endothelial-glucocorticoid signaling may play an important role in connecting depression and vascular pathology and warrants further study.
Assuntos
Doenças Cardiovasculares , Glucocorticoides , Inflamação , Humanos , Doenças Cardiovasculares/etiologia , Inflamação/imunologia , Animais , Transdução de Sinais , Células Endoteliais/metabolismo , Depressão/imunologia , Depressão/fisiopatologia , Endotélio Vascular/fisiopatologia , Receptores de Glucocorticoides/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Transtorno Depressivo Maior/imunologiaRESUMO
Schizophrenia (SCH) is a mental disorder that requires long-term antipsychotic treatment. SCH patients are thought to have an increased sensitivity to stress. The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, observed in SCH, could include altered levels of glucocorticoids, glucocorticoid receptors (GRs), and associated proteins. The perinatal administration of phencyclidine (PCP) to rodents represents an animal model of SCH. This study investigated the effects of perinatal PCP exposure and subsequent haloperidol/clozapine treatment on corticosterone levels measured by ELISA and the expression of GR-related proteins (GR, pGR, HSP70, HSP90, FKBP51, and 11ß-Hydroxysteroid dehydrogenase-11ß-HSD) determined by Western blot, in different brain regions of adult rats. Six groups of male rats were treated on the 2nd, 6th, 9th, and 12th postnatal days (PN), with either PCP or saline. Subsequently, one saline and one PCP group received haloperidol/clozapine from PN day 35 to PN day 100. The results showed altered GR sensitivity in the rat brain after PCP exposure, which decreased after haloperidol/clozapine treatment. These findings highlight disturbances in the HPA axis in a PCP-induced model of SCH and the potential protective effects of antipsychotics. To the best of our knowledge, this is the first study to investigate the effects of antipsychotic drugs on the HPA axis in a PCP animal model of SCH.
Assuntos
Antipsicóticos , Modelos Animais de Doenças , Sistema Hipotálamo-Hipofisário , Fenciclidina , Sistema Hipófise-Suprarrenal , Esquizofrenia , Animais , Fenciclidina/farmacologia , Antipsicóticos/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Esquizofrenia/induzido quimicamente , Masculino , Ratos , Receptores de Glucocorticoides/metabolismo , Corticosterona/sangue , Haloperidol/farmacologia , Haloperidol/efeitos adversos , Feminino , Clozapina/farmacologia , Ratos Sprague-DawleyRESUMO
Biological sex affects the activity of the hypothalamus-pituitary-adrenal (HPA) axis. However, how androgen deprivation affects this axis remains largely unknown. In this study, we investigated the effect of androgen status on different components of the HPA axis in male mice. Two weeks of androgen deprivation did not affect total plasma corticosterone levels but led to increased pituitary ACTH levels. Stress-induced total plasma corticosterone levels were increased, whereas the suppression of corticosterone after dexamethasone treatment under basal conditions was attenuated. Androgen-deprived mice displayed a 2-fold increase in plasma levels of corticosteroid binding globulin (CBG). A similar increase in CBG was observed in global androgen receptor knock-out animals, compared to wild-type littermates. Androgen deprivation was associated with a 6-fold increase in CBG mRNA in the liver and enhanced transcriptional activity at CBG regulatory regions, as evidenced by increased H3K27 acetylation. We propose that the induction of CBG as a consequence of androgen deprivation, together with the unaltered total corticosterone levels, results in lower free corticosterone levels in plasma. This is further supported by mRNA levels of androgen-independent GR target genes in the liver. The reduction in negative feedback on the HPA axis under basal condition would suffice to explain the enhanced stress reactivity after androgen deprivation. Overall, our data demonstrate that, in mice, tonic androgen receptor activation affects CBG levels in conjunction with effects on gene expression and HPA-axis reactivity.
Assuntos
Androgênios , Corticosterona , Sistema Hipotálamo-Hipofisário , Camundongos Knockout , Sistema Hipófise-Suprarrenal , Transcortina , Animais , Masculino , Transcortina/metabolismo , Transcortina/genética , Camundongos , Corticosterona/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Androgênios/sangue , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Fígado/efeitos dos fármacos , Hormônio Adrenocorticotrópico/sangue , Dexametasona/farmacologiaRESUMO
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of psychosis and subthreshold psychotic symptoms commonly referred to as psychotic-like experiences (PLEs). The exact mechanisms linking the HPA axis responses with the emergence of PLEs remain unknown. The present study aimed to explore real-life associations between stress, negative affect, salivary cortisol levels (a proxy of the HPA axis activity) as well as PLEs together with their underlying cognitive biases (i.e., threat anticipation and aberrant salience). The study was based on the experience sampling method scheduled over 7 consecutive days in the sample of 77 drug-naïve, young adults (18-35 years). The saliva samples were collected with each prompt to measure cortisol levels. A temporal network analysis was used to explore the directed associations of tested variables. Altogether, 3234 data entries were analyzed. Data analysis revealed that salivary cortisol levels did not directly predict next-moment fluctuations of PLEs. However, higher salivary cortisol levels were associated with higher next-moment levels of PLEs through the effects on threat anticipation and negative affect. In turn, PLEs appeared to predict cortisol levels through the effects on negative affect and event-related stress. Negative affect and threat anticipation were the most central nodes in the network. There might be bidirectional associations between the HPA axis responses and PLEs. Threat anticipation and negative affect might be the most important mediators of these associations. Interventions targeting these mediators might hold promise for disrupting the connection between the HPA axis dysregulation and PLEs.
Assuntos
Hidrocortisona , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Transtornos Psicóticos , Saliva , Humanos , Hidrocortisona/metabolismo , Hidrocortisona/análise , Masculino , Feminino , Transtornos Psicóticos/metabolismo , Transtornos Psicóticos/fisiopatologia , Adulto , Saliva/química , Saliva/metabolismo , Adulto Jovem , Adolescente , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Estresse Psicológico/metabolismo , Avaliação Momentânea EcológicaRESUMO
Vitiligo is an acquired autoimmune skin disease characterized by patchy depigmentation of the skin, often accompanied by white hair. The aetiology of vitiligo is complex and difficult to cure, and its disfiguring appearance significantly impacts patients' mental and physical health. Psychological stress is a major factor in inducing and exacerbating vitiligo, as well as affecting its treatment efficacy, though the specific mechanisms remain unclear. Increasing research on the brain-skin axis in skin immunity suggests that psychological stress can influence local skin immunity through this axis, which may play a crucial role in the pathogenesis of vitiligo. This review focuses on the role of brain-skin axis in the pathogenesis of vitiligo, and explores the possible mechanism of brain-skin axis mediating the pathogenesis of vitiligo from the aspects of sympathetic nervous system, hypothalamic-pituitary-adrenal (HPA) axis and hormones and neuropeptides, aiming to provide the necessary theoretical basis for psychological intervention in the prevention and treatment of vitiligo.
Assuntos
Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Pele , Estresse Psicológico , Vitiligo , Vitiligo/psicologia , Vitiligo/terapia , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Estresse Psicológico/imunologia , Estresse Psicológico/psicologia , Pele/patologia , Pele/imunologia , Sistema Hipófise-Suprarrenal/metabolismo , Encéfalo , Sistema Nervoso Simpático/fisiopatologia , Neuropeptídeos/metabolismoRESUMO
The hypothalamic-pituitary-ovarian (HPO) axis represents a central neuroendocrine network essential for reproductive function. Despite its critical role, the intrinsic heterogeneity within the HPO axis across vertebrates and the complex intercellular interactions remain poorly defined. This study provides the first comprehensive, unbiased, cell type-specific molecular profiling of all three components of the HPO axis in adult Lohmann layers and Liangshan Yanying chickens. Within the hypothalamus, pituitary, and ovary, seven, 12, and 13 distinct cell types were identified, respectively. Results indicated that the pituitary adenylate cyclase activating polypeptide (PACAP), follicle-stimulating hormone (FSH), and prolactin (PRL) signaling pathways may modulate the synthesis and secretion of gonadotropin-releasing hormone (GnRH), FSH, and luteinizing hormone (LH) within the hypothalamus and pituitary. In the ovary, interactions between granulosa cells and oocytes involved the KIT, CD99, LIFR, FN1, and ANGPTL signaling pathways, which collectively regulate follicular maturation. The SEMA4 signaling pathway emerged as a critical mediator across all three tissues of the HPO axis. Additionally, gene expression analysis revealed that relaxin 3 (RLN3), gastrin-releasing peptide (GRP), and cocaine- and amphetamine regulated transcripts (CART, also known as CARTPT) may function as novel endocrine hormones, influencing the HPO axis through autocrine, paracrine, and endocrine pathways. Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP, RLN3, CARTPT, LHCGR, FSHR, and GRPR in the ovaries of Lohmann layers, potentially contributing to their superior reproductive performance. In conclusion, this study provides a detailed molecular characterization of the HPO axis, offering novel insights into the regulatory mechanisms underlying reproductive biology.
Assuntos
Galinhas , Sistema Hipotálamo-Hipofisário , Ovário , Animais , Feminino , Galinhas/genética , Galinhas/fisiologia , Ovário/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , RNA-Seq , Regulação da Expressão Gênica , Hipófise/metabolismo , Transdução de SinaisRESUMO
Corticosterone, an end product of the hypothalamic-pituitary-adrenal (HPA) axis, is a crucial stress hormone. A dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders, such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.
Assuntos
Ansiedade , Carnosina , Corticosterona , Suplementos Nutricionais , Camundongos Knockout , Estresse Psicológico , Animais , Corticosterona/sangue , Carnosina/farmacologia , Masculino , Camundongos , Modelos Animais de Doenças , Transtorno do Espectro Autista , Comportamento Animal/efeitos dos fármacos , Administração Oral , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Proteínas Ligadas por GPI/metabolismoRESUMO
In clinical endocrinology, it is often assumed that the results of thyroid hormone function tests (TFTs) before total thyroidectomy are considered euthyroid when the circulating concentrations of thyrotropin [TSH] and free thyroxine [FT4] are within the normal reference ranges. Postoperative thyroid replacement therapy with levothyroxine. The aim of L-T4 is to reproduce the preoperative euthyroid condition. Currently, intra-individual changes in the euthyroid set point before and after total thyroidectomy are only partly understood. After total thyroidectomy, a greater postoperative [FT4] than preoperative [FT4] for equivalent euthyroid [TSH] was found, with differences ranging from 3 to 8 pmol/L. This unexplained difference can be explained by the use of a mathematical model of the hypothalamus-pituitary-thyroid (HPT) axis set point theory. In this article, the postoperative HPT euthyroid set point was calculated using a dataset of total thyroidectomized patients with at least three distinguishable postoperative TFTs. The postoperative [TSH] set point was used as a homeostatic reference for the comparison of preoperative TFTs. The preoperative [FT4] value was equal to the postoperative [FT4] value in 50% of the patients, divided by a factor of ~ 1.25 (within +/- 10%). The factor of 1.25 stems from the lack of postoperative use of thyroidal triiodothyronine (T3). Furthermore, approximately 25% of the patients presented a greater preoperative [FT4] difference than postoperative [FT4]/1.25 combined with a normal [TSH] difference. Based on these observations, the effect of T3 on the value of the [FT4] set point was analyzed and explained from a control theory perspective.
Assuntos
Glândula Tireoide , Tireoidectomia , Tiroxina , Tri-Iodotironina , Humanos , Tiroxina/sangue , Tri-Iodotironina/sangue , Glândula Tireoide/cirurgia , Glândula Tireoide/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Tireotropina/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Testes de Função Tireóidea/métodos , Adulto , Hipófise/metabolismo , Hipófise/cirurgia , Idoso , Hipotálamo/metabolismoRESUMO
Research into the impacts of oxidative stress (OS), and hormonal balance on reproductive potential has increased over the last 40 years possibly due to rising male infertility. Decreased antioxidant levels and increased OS in tissues result from hormonal imbalance, which in turn leads to male infertility. Increased reactive oxygen species (ROS) generation in seminal plasma has been linked to many lifestyle factors such as alcohol and tobacco use, toxicant exposure, obesity, varicocele, stress, and aging. This article provides an overview of the crosslink between OS and gonadal hormone disruption, as well as a potential mode of action in male infertility. Disrupting the equilibrium between ROS generation and the antioxidant defense mechanism in the male reproductive system may affect key hormonal regulators of male reproductive activities. Unchecked ROS production may cause direct injury on reproductive tissues or could disrupt normal regulatory mechanisms of the hypothalamic-pituitary-gonadal (HPG) axis and its interaction with other endocrine axes, both of which have negative effects on male reproductive health and can lead to male infertility.
Assuntos
Infertilidade Masculina , Estresse Oxidativo , Reprodução , Masculino , Humanos , Estresse Oxidativo/fisiologia , Infertilidade Masculina/metabolismo , Infertilidade Masculina/etiologia , Infertilidade Masculina/fisiopatologia , Animais , Reprodução/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismoRESUMO
Depressive pseudodementia (DPD) is a debilitating cognitive dysfunction that accompanies major and/or frequent depressive attacks. DPD has gained significant research attention owing to its negative effects on the patients' quality of life and productivity. This study tested the procognitive potential of Flibanserin (FBN), the serotonin (5HT) receptor modulator, against propranolol (PRP), as ß/5HT1A receptors blocker. Serving this purpose, female Wistar Albino rats were subjected to chronic unpredictable stress (CUS) and subsequently treated with FBN only (3 mg/kg/day, p.o), PRP only (10 mg/kg/day, p.o), or PRP followed by FBN, using the same doses. FBN ameliorated the behavioral/cognitive alterations and calmed the hypothalamic-pituitary-adrenal (HPA) axis storm by reducing the levels of stress-related hormones, viz, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT) parallel to epinephrine (EPI) hyperstimulation. The maladaptive inflammatory response, comprising of interleukin (IL)-1ß/6, and tumor necrosis factor (TNF)-α, was consequently blunted. This was contemporaneous to the partial restoration of the protein kinase-B (AKT)/glycogen synthase kinase (GSK)3ß/signal transducer and activator of transcription (STAT)-3 survival trajectory and the reinstatement of the levels of brain derived neurotrophic factor (BDNF). Microscopically, FBN repaired the hippocampal architecture and lessened CD68/GFAP immunoreactivity. Pre-administration of PRP partially abolished FBN effect along the estimated parameters, except for 5HT2A receptor expression and epinephrine level, to prove 5HT1A receptor as a fulcrum initiator of the investigated pathway, while its sole administration worsened the underlying condition. Ultimately, these findings highlight the immense procognitive potential of FBN, offering a new paradigm for halting DPD advancement via synchronizing adrenergic/serotonergic circuitry.
Assuntos
Benzimidazóis , Fator Neurotrófico Derivado do Encéfalo , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Proteínas Proto-Oncogênicas c-akt , Ratos Wistar , Animais , Feminino , Ratos , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Modelos Animais de Doenças , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Inflamação/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serotonina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/complicações , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêuticoRESUMO
Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic-pituitary-adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3ß-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE.
Assuntos
Encefalomielite Autoimune Experimental , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Animais , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Feminino , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Sistema Hipotálamo-Hipofisário/metabolismo , Corticosterona/sangue , Hormônio Adrenocorticotrópico/sangue , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Caracteres Sexuais , Progesterona/sangueRESUMO
Postpartum depression (PPD) affects 174 million women worldwide and is characterized by profound sadness, anxiety, irritability, and debilitating fatigue, which disrupt maternal caregiving and the mother-infant relationship. Limited pharmacological interventions are currently available. Our understanding of the neurobiological pathophysiology of PPD remains incomplete, potentially hindering the development of novel treatment strategies. Recent hypotheses suggest that PPD is driven by a complex interplay of hormonal changes, neurotransmitter imbalances, inflammation, genetic factors, psychosocial stressors, and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This narrative review examines recent clinical studies on PPD within the past 15 years, emphasizing advancements in neuroimaging findings and blood biomarker detection. Additionally, we summarize recent laboratory work using animal models to mimic PPD, focusing on hormone withdrawal, HPA axis dysfunction, and perinatal stress theories. We also revisit neurobiological results from several brain regions associated with negative emotions, such as the amygdala, prefrontal cortex, hippocampus, and striatum. These insights aim to improve our understanding of PPD's neurobiological mechanisms, guiding future research for better early detection, prevention, and personalized treatment strategies for women affected by PPD and their families.
Assuntos
Biomarcadores , Depressão Pós-Parto , Humanos , Depressão Pós-Parto/metabolismo , Feminino , Animais , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Estresse Psicológico/metabolismoRESUMO
Recent research has extensively explored the intricate mechanisms that underlie the effectiveness of acupuncture, highlighting the importance of stimulating acupoints, the role of acupuncture techniques in managing diseases, and the interaction between meridian pathways and molecular processes. Studies have underscored the crucial role of acupuncture in activating neurons, modulating the immune system, and influencing vascular activity, all of which contribute significantly to its therapeutic benefits across a wide range of symptoms and conditions. Utilization of imaging modalities enables the identification of changes in cerebral blood flow, brain function, and regional glucose metabolism following acupuncture sessions. The interstitial fluid circulation network within meridians adheres to specific laws that facilitate the transportation of materials. Acupuncture initiates the release of neurotransmitters, neuropeptides, and immune factors, impacting pain perception, inflammation, and physiological functions. It influences the complex neuro-endocrine-immune network by activating pathways involving the nervous system, the hypothalamic-pituitary-adrenal axis, and immune responses. Moreover, acupuncture induces molecular modifications such as phosphorylation, methylation, and histone modification, leading to key molecular changes that ultimately result in anti-inflammatory effects and the regulation of immune responses.