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The COVID-19 pandemic has highlighted structural inequalities and racism promoting health disparities among communities of color. Taking cardiovascular disease as an example, we provide a framework for multidisciplinary efforts leveraging translational and epidemiologic approaches to decode the biological impacts of inequalities and racism and develop targeted interventions that promote health equity.
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COVID-19/epidemiología , Equidad en Salud , Promoción de la Salud/métodos , Racismo , Estrés Fisiológico/inmunología , COVID-19/inmunología , COVID-19/metabolismo , COVID-19/psicología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/inmunología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/psicología , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/inmunología , Regulación de la Expresión Génica/fisiología , Humanos , Sistema Hipotálamo-Hipofisario/inmunología , Sistema Hipotálamo-Hipofisario/fisiología , Racismo/psicología , Factores de Riesgo , Sistema Nervioso Simpático/inmunología , Sistema Nervioso Simpático/fisiologíaRESUMEN
In humans, as in the other mammals, the neuroendocrine control of reproduction is ensured by the brain-pituitary gonadotropic axis. Multiple internal and environmental cues are integrated via brain neuronal networks, ultimately leading to the modulation of the activity of gonadotropin-releasing hormone (GnRH) neurons. The decapeptide GnRH is released into the hypothalamic-hypophysial portal blood system and stimulates the production of pituitary glycoprotein hormones, the two gonadotropins luteinizing hormone and follicle-stimulating hormone. A novel actor, the neuropeptide kisspeptin, acting upstream of GnRH, has attracted increasing attention in recent years. Other neuropeptides, such as gonadotropin-inhibiting hormone/RF-amide related peptide, and other members of the RF-amide peptide superfamily, as well as various nonpeptidic neuromediators such as dopamine and serotonin also provide a large panel of stimulatory or inhibitory regulators. This paper addresses the origin and evolution of the vertebrate gonadotropic axis. Brain-pituitary neuroendocrine axes are typical of vertebrates, the pituitary gland, mediator and amplifier of brain control on peripheral organs, being a vertebrate innovation. The paper reviews, from molecular and functional perspectives, the evolution across vertebrate radiation of some key actors of the vertebrate neuroendocrine control of reproduction and traces back their origin along the vertebrate lineage and in other metazoa before the emergence of vertebrates. A focus is given on how gene duplications, resulting from either local events or from whole genome duplication events, and followed by paralogous gene loss or conservation, might have shaped the evolutionary scenarios of current families of key actors of the gonadotropic axis.
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Evolución Molecular , Duplicación de Gen , Genoma Humano , Gonadotropinas/genética , Gónadas/fisiología , Sistema Hipotálamo-Hipofisario/fisiología , Células Neuroendocrinas/fisiología , Reproducción/genética , Animales , Gonadotropinas/metabolismo , Gónadas/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Células Neuroendocrinas/metabolismo , Filogenia , Especificidad de la EspecieRESUMEN
The hypothalamic-pituitary-thyroid (HPT) axis is fundamental to human biology, exerting central control over energy expenditure and body temperature. However, the consequences of normal physiologic HPT-axis variation in populations without diagnosed thyroid disease are poorly understood. Using nationally representative data from the 2007 to 2012 National Health and Nutrition Examination Survey, we explore relationships with demographic characteristics, longevity, and socio-economic factors. We find much larger variation across age in free T3 than other HPT-axis hormones. T3 and T4 have opposite relationships to mortality: free T3 is inversely related and free T4 is positively related to the likelihood of death. Free T3 and household income are negatively related, particularly at lower incomes. Finally, free T3 among older adults is associated with labor both in terms of unemployment and hours worked. Physiologic TSH/T4 explain only 1.7% of T3 variation, and neither are appreciably correlated to socio-economic outcomes. Taken together, our data suggest an unappreciated complexity of the HPT-axis signaling cascade broadly such that TSH and T4 may not be accurate surrogates of free T3. Furthermore, we find that subclinical variation in the HPT-axis effector hormone T3 is an important and overlooked factor linking socio-economic forces, human biology, and aging.
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Glándula Tiroides , Triyodotironina , Humanos , Anciano , Longevidad , Estatus Económico , Encuestas Nutricionales , Sistema Hipotálamo-Hipofisario/fisiología , Tirotropina , Demografía , TiroxinaRESUMEN
Despite significant research on the effects of stress on the hypothalamic-pituitary-adrenal (HPA) axis, questions remain regarding long-term impacts of large-scale stressors. Leveraging data on exposure to an unanticipated major natural disaster, the 2004 Indian Ocean tsunami, we provide causal evidence of its imprint on hair cortisol levels fourteen years later. Data are drawn from the Study of the Tsunami Aftermath and Recovery, a population-representative longitudinal study of tsunami survivors who were living along the coast of Aceh, Indonesia, when the tsunami hit. Annual rounds of data, collected before, the year after and 2 y after the disaster provide detailed information about tsunami exposures and self-reported symptoms of post-traumatic stress. Hair samples collected 14 y after the tsunami from a sample of adult participants provide measures of cortisol levels, integrated over several months. Hair cortisol concentrations are substantially and significantly lower among females who were living, at the time of the tsunami, in communities directly damaged by the tsunami, in comparison with similar females living in other, nearby communities. Differences among males are small and not significant. Cortisol concentrations are lowest among those females living in damaged communities who reported elevated post-traumatic stress symptoms persistently for two years after the tsunami, indicating that the negative effects of exposure were largest for them. Low cortisol is also associated with contemporaneous reports of poor self-rated general and psychosocial health. Taken together, the evidence points to dysregulation in the HPA axis and "burnout" among these females fourteen years after exposure to the disaster.
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Agotamiento Psicológico , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Tsunamis , Adulto , Femenino , Humanos , Masculino , Hidrocortisona , Sistema Hipotálamo-Hipofisario/fisiología , Océano Índico , Estudios Longitudinales , Sistema Hipófiso-Suprarrenal/fisiología , Agotamiento Psicológico/fisiopatologíaRESUMEN
The hypothalamic-pituitary-gonadal axis (HPG) is the key neuroendocrine axis involved in reproductive regulation. Brain and muscle ARNT-like protein 1 (Bmal1) participates in regulating the metabolism of various endocrine hormones. However, the regulation of Bmal1 on HPG and female fertility is unclear. This study aims to explore the regulation of female reproduction by Bmal1 via the HPG axis in mice. Bmal1-knockout (Ko) mice were generated using the CRISPR/Cas9 technology. The structure, function, and estrous cycle of ovarian in Bmal1 Ko female mice were measured. The key genes and proteins of the HPG axis involved in regulating female reproduction were examined through transcriptome analysis and then verified by RT-PCR, immunohistochemistry, and western blot. Furthermore, the fertility of female mice was detected after intervening prolactin (PRL) and progesterone (Pg) in Bmal1 ko mice. The number of offspring and ovarian weight were significantly lower in Bmal1-Ko mice than in wild-type (Wt) mice. In Bmal1-Ko mice, ovarian cells were arranged loosely and irregularly, and the total number of follicles was significantly reduced. No corpus luteum was found in the ovaries. Vaginal smears revealed that Bmal1-Ko mice had an irregular estrus cycle. In Bmal1-Ko mice, Star expression was decreased, PRL and luteinizing hormone (LH) levels were increased, and dopamine (DA) and Pg levels were decreased. Inhibition of PRL partially recovered the estrous cycle, corpus luteum formation, and Star expression in the ovaries. Pg supplementation promoted embryo implantation in Bmal1-Ko female mice. Bmal1 Ko increases serum PRL levels in female mice likely by reducing DA levels, thus affecting luteal formation, resulting in decreased Star expression and Pg production, hindering female reproduction. Inhibition of PRL or restoration of Pg can partially restore reproductive capacity in female Bmal1-Ko mice. Thus, Bmal1 may regulate female reproduction via the HPG axis in mice, suggesting that Bmal1 is a potential target to treat female infertility.
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Factores de Transcripción ARNTL , Sistema Hipotálamo-Hipofisario , Ovario , Reproducción , Animales , Femenino , Ratones , Factores de Transcripción ARNTL/metabolismo , Factores de Transcripción ARNTL/genética , Ciclo Estral , Fertilidad , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Ratones Endogámicos C57BL , Ratones Noqueados , Ovario/metabolismo , Progesterona/metabolismo , Prolactina/metabolismoRESUMEN
The circadian timing system and integrated stress response (ISR) systems are fundamental regulatory mechanisms that maintain body homeostasis. The central circadian pacemaker in the suprachiasmatic nucleus (SCN) governs daily rhythms through interactions with peripheral oscillators via the hypothalamus-pituitary-adrenal (HPA) axis. On the other hand, ISR signaling is pivotal for preserving cellular homeostasis in response to physiological changes. Notably, disrupted circadian rhythms are observed in cases of impaired ISR signaling. In this work, we examine the potential interplay between the central circadian system and the ISR, mainly through the SCN and HPA axis. We introduce a semimechanistic mathematical model to delineate SCN's capacity for indirectly perceiving physiological stress through glucocorticoid-mediated feedback from the HPA axis and orchestrating a cellular response via the ISR mechanism. Key components of our investigation include evaluating general control nonderepressible 2 (GCN2) expression in the SCN, the effect of physiological stress stimuli on the HPA axis, and the interconnected feedback between the HPA and SCN. Simulation revealed a critical role for GCN2 in linking ISR with circadian rhythms. Experimental findings have demonstrated that a Gcn2 deletion in mice leads to rapid re-entrainment of the circadian clock following jetlag as well as to an elongation of the circadian period. These phenomena are well replicated by our model, which suggests that both the swift re-entrainment and prolonged period can be ascribed to a reduced robustness in neuronal oscillators. Our model also offers insights into phase shifts induced by acute physiological stress and the alignment/misalignment of physiological stress with external light-dark cues. Such understanding aids in strategizing responses to stressful events, such as nutritional status changes and jetlag.NEW & NOTEWORTHY This study is the first theoretical work to investigate the complex interaction between integrated stress response (ISR) sensing and central circadian rhythm regulation, encompassing the suprachiasmatic nucleus (SCN) and hypothalamus-pituitary-adrenal (HPA) axis. The findings carry implications for the development of dietary or pharmacological interventions aimed at facilitating recovery from stressful events, such as jetlag. Moreover, they provide promising prospects for potential therapeutic interventions that target circadian rhythm disruption and various stress-related disorders.
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Ritmo Circadiano , Simulación por Computador , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Proteínas Serina-Treonina Quinasas , Estrés Fisiológico , Núcleo Supraquiasmático , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Animales , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipófiso-Suprarrenal/fisiología , Núcleo Supraquiasmático/fisiología , Núcleo Supraquiasmático/metabolismo , Ritmo Circadiano/fisiología , Ratones , Estrés Fisiológico/fisiología , Proteínas Serina-Treonina Quinasas/metabolismo , Relojes Circadianos/fisiología , Transducción de Señal/fisiologíaRESUMEN
PURPOSE: Previous studies have shown differences in baseline and stimulated cortisol levels between men and women. Whether this difference is secondary to sex hormones or to other factors, such as genetic or epigenetic changes, is unknown. We investigated the effect of gender-affirming hormone treatment (GAHT) on the hypothalamo-pituitary-adrenal axis of transgender subjects in an effort to throw light on this question. METHODS: Ten transgender males (TM) and eight transgender females (TF) underwent a low-dose (1 µg) adrenocorticotropic hormone (ACTH) stimulation test before and 6 months after GAHT initiation. Serum total, free and salivary cortisol (SC) levels were measured at baseline and at 20, 30 and 40 min. RESULTS: For the TM, all three levels were significantly lower at several time points after ACTH injection compared to pretreatment levels following 6 months of treatment (p < .05). Likewise, the overall SC response as calculated by the area under the curve was significantly lower (p = .0053). For the TF, the basal total cortisol (TC) level increased after 6 months of treatment (p < .01) while ACTH-stimulated SC levels decreased significantly. The basal ACTH levels were significantly lower following hormonal therapy (p < .001). CONCLUSION: Stimulated salivary cortisol levels decreased significantly after 6 months of GAHT in both male and female transgender subjects, possibly reflecting a decreased state of anxiety associated with treatment initiation. Additionally, basal and stimulated serum TC levels increased after hormonal treatment in the TF, probably secondary to the effect of oestrogen on cortisol-binding globulin.
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Hormona Adrenocorticotrópica , Hidrocortisona , Humanos , Femenino , Masculino , Hormonas Esteroides Gonadales , Hipófisis , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal/fisiologíaRESUMEN
Experiencing early life adversity (ELA) alters stress physiology and increases the risk for developing psychiatric disorders. The social environment can influence dynamics of stress responding and buffer and/or transfer stress across individuals. Yet, the impact of ELA on sensitivity to the stress of others and social behavior following stress is unknown. Here, to test the impact of ELA on social and physiological responses to stress, circulating blood corticosterone (CORT) and social behaviors were assessed in adult male and female mice reared under limited bedding and nesting (LBN) or control conditions. To induce stress, one cagemate of a pair-housed cage underwent a footshock paradigm and was then returned to their unshocked partner. CORT was measured in both groups of mice 20 or 90 min after stress exposure, and social behaviors were recorded and analyzed. ELA rearing influenced the CORT response to stress in a sex-specific manner. In males, both control and ELA-reared mice exhibited similar stress transfer to unshocked cagemates and similar CORT dynamics. In contrast, ELA females showed a heightened stress transfer to unshocked cagemates, and sustained elevation of CORT relative to controls, indicating enhanced stress contagion and a failure to terminate the stress response. Behaviorally, ELA females displayed decreased allogrooming and increased investigative behaviors, while ELA males showed reduced huddling. Together, these findings demonstrate that ELA influenced HPA axis dynamics, social stress contagion and social behavior. Further research is needed to unravel the underlying mechanisms and long-term consequences of ELA on stress systems and their impact on behavioral outcomes.
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Experiencias Adversas de la Infancia , Corticosterona , Humanos , Adulto , Ratones , Masculino , Animales , Femenino , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal/fisiología , Estrés Psicológico/psicologíaRESUMEN
Social environments modulate endocrine function, yet it is unclear whether individuals can become like their social partners in how they physiologically respond to stressors. This social transmission of hypothalamic-pituitary-adrenal (HPA) axis reactivity could have long-term consequences for health and lifespan of individuals if their social partners react to stressors with an exaggerated HPA axis response. We tested whether glucocorticoid levels in response to stress of breeding partners changes after breeding depending on whether partners had similar or dissimilar postnatal conditions. We manipulated postnatal conditions by mimicking early life stress in zebra finch chicks (Taeniopygia guttata) via postnatal corticosterone exposure. When they reached adulthood, we created breeding pairs where the female and male had experienced either the same or different early life hormonal treatment (corticosterone or control). Before and after breeding, we obtained blood samples within 3 min and after 10 min or 30 min of restraint stress (baseline, cort10, cort30). We found that corticosterone levels of individuals in response to restraint were affected by their own and their partner's early life conditions, but did not change after breeding. However, across all pairs, partners became more similar in cort30 levels after breeding, although differences between partners in cort10 remained greater in pairs with a corticosterone-treated female. Thus, we show that HPA axis response to stressors in adulthood can be modulated by reproductive partners and that similarity between partners is reduced when females are postnatally exposed to elevated glucocorticoids.
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Corticosterona , Pinzones , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Estrés Psicológico , Animales , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipotálamo-Hipofisario/metabolismo , Femenino , Sistema Hipófiso-Suprarrenal/fisiología , Sistema Hipófiso-Suprarrenal/metabolismo , Masculino , Corticosterona/sangre , Estrés Psicológico/metabolismo , Estrés Psicológico/sangre , Pinzones/fisiología , Reproducción/fisiología , Restricción Física/fisiologíaRESUMEN
Social status directly affects the health of humans and other animals. Low status individuals receive more antagonistic encounters, have fewer supportive relationships and have worse health outcomes. However, the physiological and cellular processes that mediate the relationship between the social environment and health are incompletely known. Epigenetic regulation of the hypothalamic-pituitary-adrenal (HPA) axis, the neuroendocrine pathway that activates in response to stressors, may be one process that is sensitive to the social environment. Here, we experimentally manipulated plumage, a key social signal in female tree swallows (Tachycineta bicolor) and quantified methylation of four genes in the HPA axis before and after treatment. We found that dulling the white breast plumage affected methylation in one gene, CRHR1; however, the effect depended on the original brightness of the bird. Methylation in this gene was correlated with baseline corticosterone levels, suggesting that DNA methylation of CRHR1 helps regulate glucocorticoid production in this species. Methylation in two other genes, FKBP5 and GR, changed over the course of the experiment, independent of treatment. These results show that methylation of these genes is labile into adulthood and suggest that epigenetic regulation of the HPA axis could help birds respond to current environmental conditions.
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Metilación de ADN , Plumas , Sistema Hipotálamo-Hipofisario , Receptores de Hormona Liberadora de Corticotropina , Golondrinas , Animales , Femenino , Plumas/fisiología , Golondrinas/genética , Golondrinas/fisiología , Receptores de Hormona Liberadora de Corticotropina/genética , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Proteínas de Unión a Tacrolimus/genética , Proteínas de Unión a Tacrolimus/metabolismo , Corticosterona/sangre , Corticosterona/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipófiso-Suprarrenal/fisiología , Epigénesis Genética , Estrés Fisiológico/genética , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Proteínas Aviares/genética , Proteínas Aviares/metabolismoRESUMEN
Social bonds increase fitness in a range of mammals. One pathway by which social bonds may increase fitness is by reducing the exposure to physiological stress, i.e. glucocorticoid (GC) hormones, that can be detrimental to health and survival. This is achieved through downregulating hypothalamic-pituitary-adrenal (HPA)-axis activity. Indeed, long-term measures of social (grooming) bonds are often negatively correlated with HPA-axis activity. However, the proximate role of physical touch through allogrooming remains an open question in the sociality-health-fitness debate. Demonstrating the potential anxiolytic benefits of grooming in the wild is hindered by methodological limitations. Here, we match accelerometer-identified grooming in wild female chacma baboons (Papio ursinus) to non-invasive faecal GC metabolite concentrations (fGCs). Consistent with previous work, we found a negative (but statistically non-significant) overall relationship between individual averaged fGCs and grooming rates. However, when time-matching grooming to fGCs, we found that both more giving and receiving grooming were followed by higher fGCs. This upregulation of HPA-axis activity suggests that maintaining social bonds (and its ultimate fitness benefits) may come at a shorter-term physiological cost. This finding sheds new light on a ubiquitous social behaviour typically considered 'relaxing' and suggests that sociopositive contact can trigger physiological stress.
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Aseo Animal , Estrés Fisiológico , Animales , Femenino , Heces/química , Glucocorticoides/metabolismo , Conducta Social , Papio ursinus/fisiología , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal/fisiologíaRESUMEN
Important sex-related differences have been observed in the onset, prevalence, and clinical phenotype of depression, based on several epidemiological studies. Social, behavioural, and educational factors have a great role in underlying this bias; however, also several biological factors are extensively involved. Indeed, sexually dimorphic biological systems might represent the underlying ground for these disparities, including cerebral structures and neural correlates, reproductive hormones, stress response pathways, the immune system and inflammatory reaction, metabolism, and fat distribution. Furthermore, in this perspective, it is also important to consider and focus the attention on specific ages and life stages of individuals: indeed, women experience during their life specific periods of reproductive transitional phases, which are not found in men, that represent windows of particular psychological vulnerability. In addition to these, other biologically related risk factors, including the occurrence of sleep disturbances and the exposure to childhood trauma, which are found to differentially affect men and women, are also putative underlying mechanisms of the clinical bias of depression. Overall, by taking into account major differences which characterize men and women it might be possible to improve the diagnostic process, as well as treat more efficiently depressed individuals, based on a more personalized medicine and research.
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Depresión , Hormonas , Masculino , Humanos , Femenino , Depresión/etiología , Factores de Riesgo , Caracteres Sexuales , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal , Factores SexualesRESUMEN
Hosts of the same species vary in physiological responses to the same parasite, and some groups of individuals can disproportionately affect disease dynamics; however, the underlying pathophysiology of host-parasite interactions is poorly understood in wildlife. We tested the hypothesis that the hypothalamic-pituitary-adrenal (HPA) axis mediates host resistance and tolerance to avian malaria during the acute phase of infection by evaluating whether individual variation in circulating glucocorticoids predicted resistance to avian malaria in a songbird. We experimentally inoculated wild-caught house sparrows (Passer domesticus) with naturally sourced Plasmodium relictum and quantified baseline and restraint-induced circulating corticosterone, negative feedback ability, cellular and humoral immune function, and baseline and restraint-induced glycemia, prior to and during acute malaria infection. During peak parasitemia, we also evaluated the expression of several liver cytokines that are established pathological hallmarks of malaria in mammals: two pro-inflammatory (IFN-γ and TNF-α) and two anti-inflammatory (IL-10 and TGF-ß). Although most of the host metrics we evaluated were not correlated with host resistance or tolerance to avian malaria, this experiment revealed novel relationships between malarial parasites and the avian immune system that further our understanding of the pathology of malaria infection in birds. Specifically, we found that: (1) TNF-α liver expression was positively correlated with parasitemia; (2) sparrows exhibited an anti-inflammatory profile during malaria infection; and (3) IFN-γ and circulating glucose were associated with several immune parameters, but only in infected sparrows. We also found that, during the acute phase of infection, sparrows increased the strength of corticosterone negative feedback at the level of the pituitary. In the context of our results, we discuss future methodological considerations and aspects of host physiology that may confer resistance to avian malaria, which can help inform conservation and rehabilitation strategies for avifauna at risk.
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Malaria Aviar , Malaria , Plasmodium , Gorriones , Humanos , Animales , Gorriones/fisiología , Malaria Aviar/parasitología , Sistema Hipotálamo-Hipofisario/fisiología , Corticosterona , Parasitemia/parasitología , Factor de Necrosis Tumoral alfa , Sistema Hipófiso-Suprarrenal/fisiología , Plasmodium/fisiología , Malaria/parasitología , Malaria/veterinaria , Antiinflamatorios , MamíferosRESUMEN
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.
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Hidrocortisona , Pubertad , Humanos , Femenino , Hidrocortisona/metabolismo , Adolescente , Niño , Estudios Longitudinales , Pubertad/fisiología , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/crecimiento & desarrolloRESUMEN
Human aging is associated with senescence of the hypothalamic-pituitary-adrenal (HPA) axis, leading to progressive dysregulation characterized by increased cortisol exposure. This key hormone is implicated in the pathogenesis of many age-related diseases. Common marmosets (Callithrix jacchus) display a wide spectrum of naturally occurring age-related pathologies that compare similarly to humans and are increasingly used as translational models of aging and age-related disease. Whether the marmoset HPA axis also shows senescence with increasing age is unknown. We analyzed hair cortisol concentration (HCC) across the lifespan of 50 captive common marmosets, ranging in age from approximately 2 months-14.5 years, via a cross-sectional design. Samples were processed and analyzed for cortisol using enzyme immunoassay. HCC ranged from 1416 to 15,343 pg/mg and was negatively correlated with age. We found significant main effects of age group (infant, adolescent, adult, aged, very aged) and sex on HCC, and no interaction effects. Infants had significantly higher levels of HCC compared with all other age groups. Females had higher HCC than males. There was no interaction between age and sex. These results suggest marmosets do not show dysregulation of the HPA axis with increasing age, as measured via HCC.
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Callithrix , Hidrocortisona , Masculino , Femenino , Humanos , Animales , Callithrix/fisiología , Longevidad , Sistema Hipotálamo-Hipofisario/fisiología , Estudios Transversales , Sistema Hipófiso-Suprarrenal/fisiologíaRESUMEN
Developmental plasticity is particularly important for humans and other primates because of our extended period of growth and maturation, during which our phenotypes adaptively respond to environmental cues. The hypothalamus-pituitary-gonadal (HPG) and hypothalamus-pituitary-adrenal (HPA) axes are likely to be principal targets of developmental "programming" given their roles in coordinating fitness-relevant aspects of the phenotype, including sexual development, adult reproductive and social strategies, and internal responses to the external environment. In social animals, including humans, the social environment is believed to be an important source of cues to which these axes may adaptively respond. The effects of early social environments on the HPA axis have been widely studied in humans, and to some extent, in other primates, but there are still major gaps in knowledge specifically relating to males. There has also been relatively little research examining the role that social environments play in developmental programming of the HPG axis or the HPA/HPG interface, and what does exist disproportionately focuses on females. These topics are likely understudied in males in part due to the difficulty of identifying developmental milestones in males relative to females and the general quiescence of the HPG axis prior to maturation. However, there are clear indicators that early life social environments matter for both sexes. In this review, we examine what is known about the impact of social environments on HPG and HPA axis programming during male development in humans and nonhuman primates, including the role that epigenetic mechanisms may play in this programming. We conclude by highlighting important next steps in this research area.
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Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Primates , Medio Social , Animales , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipófiso-Suprarrenal/fisiología , Masculino , Primates/fisiología , Humanos , FemeninoRESUMEN
OBJECTIVE: Less than half of servicewomen report loss of menses during initial military training. However, self-reported menstrual status may not accurately reflect hypothalamic-pituitary-ovarian (HPO) axis suppression and may underestimate reproductive health consequences of military training. Our aim was to characterise HPO axis function during US Army Basic Combat Training (BCT) in non-hormonal contraceptive-using women and explore potential contributors to HPO axis suppression. METHODS: In this 10-week prospective observational study, we enrolled multi-ethnic women entering BCT. Trainees provided daily first-morning voided urine, and weekly blood samples during BCT. Urinary luteinising hormone, follicle stimulating hormone, and metabolites of estradiol and progesterone were measured by chemiluminescent assays (Siemens Centaur XP) to determine hormone patterns and luteal activity. We measured body composition, via dual-energy X-ray absorptiometry, at the beginning and end of BCT. RESULTS: Trainees (n=55) were young (mean (95% CI): 22 (22, 23) years) with average body mass index (23.9 (23.1, 24.7) kg/m2). Most trainees (78%) reported regular menstrual cycles before BCT. During BCT, 23 (42%) trainees reported regular menses. However, only seven trainees (12.5%) had menstrual cycles with evidence of luteal activity (ELA) (ie, presumed ovulation), all with shortened luteal phases. 41 trainees (75%) showed no ELA (NELA), and 7 (12.5%) were categorised as indeterminant. Overall, women gained body mass and lean mass, but lost fat mass during BCT. Changes in body mass and composition appear unrelated to luteal activity. CONCLUSIONS: Our findings reveal profound HPO axis suppression with NELA in the majority of women during BCT. This HPO axis suppression occurs among women who report normal menstrual cycles.
Asunto(s)
Estradiol , Sistema Hipotálamo-Hipofisario , Personal Militar , Progesterona , Humanos , Femenino , Estudios Prospectivos , Adulto Joven , Sistema Hipotálamo-Hipofisario/fisiología , Progesterona/sangre , Estradiol/sangre , Ovario/fisiología , Hormona Luteinizante/sangre , Hormona Folículo Estimulante/sangre , Composición Corporal/fisiología , Estados Unidos , Ciclo Menstrual/fisiología , Adulto , Menstruación/fisiología , Acondicionamiento Físico Humano/fisiologíaRESUMEN
Assessing the physiological stress responses of wild animals opens a window for understanding how organisms cope with environmental challenges. Since stress response is associated with changes in body temperature, the use of body surface temperature through thermal imaging could help to measure acute and chronic stress responses non-invasively. We used thermal imaging, acute handling-stress protocol and an experimental manipulation of corticosterone (the main glucocorticoid hormone in birds) levels in breeding king penguins (Aptenodytes patagonicus), to assess: 1. The potential contribution of the Hypothalamo-Pituitary-Adrenal (HPA) axis in mediating chronic and acute stress-induced changes in adult surface temperature, 2. The influence of HPA axis manipulation on parental investment through thermal imaging of eggs and brooded chicks, and 3. The impact of parental treatment on offspring thermal's response to acute handling. Maximum eye temperature (Teye) increased and minimum beak temperature (Tbeak) decreased in response to handling stress in adults, but neither basal nor stress-induced surface temperatures were significantly affected by corticosterone implant. While egg temperature was not significantly influenced by parental treatment, we found a surprising pattern for chicks: chicks brooded by the (non-implanted) partner of corticosterone-implanted individuals exhibited higher surface temperature (both Teye and Tbeak) than those brooded by glucocorticoid-implanted or control parents. Chick's response to handling in terms of surface temperature was characterized by a drop in both Teye and Tbeak independently of parental treatment. We conclude that the HPA axis seems unlikely to play a major role in determining chronic or acute changes in surface temperature in king penguins. Changes in surface temperature may primarily be mediated by the Sympathetic-Adrenal-Medullary (SAM) axis in response to stressful situations. Our experiment did not reveal a direct impact of parental HPA axis manipulation on parental investment (egg or chick temperature), but a potential influence on the partner's brooding behaviour.
Asunto(s)
Corticosterona , Sistema Hipotálamo-Hipofisario , Spheniscidae , Estrés Fisiológico , Animales , Spheniscidae/fisiología , Spheniscidae/sangre , Corticosterona/sangre , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipotálamo-Hipofisario/metabolismo , Femenino , Masculino , Sistema Hipófiso-Suprarrenal/fisiología , Sistema Hipófiso-Suprarrenal/metabolismo , Temperatura CorporalRESUMEN
Noise, as an unavoidable stress (pressure) source in the modern life, affects animals in many ways, both behaviorally and physiologically. Behavioral changes may be driven by changes in hormone secretion in animals. When animals face with noise stress, the neuroendocrine systems, mainly the hypothalamic-pituitary-adrenal (HPA) axis, are activated, which promotes the secretion and release of stress hormones, and then leads to a series of behavioral changes. The behavioral changes can be easily observed, but the changes in physiological indicators such as hormone levels need to be accurately measured. Currently, many studies have measured the variations of stress hormone levels in animals under different noise conditions. Taking glucocorticoid as an example, this paper summarizes the different measurement methods of stress hormones, especially the non-invasive measurement methods, and compares the advantages and shortcomings of them. It provides a variety of measurement choices for the study of related issues, and also helps us to further understand the sources of animal stress, in order to provide a better habitat for animals.
Asunto(s)
Sistema Hipotálamo-Hipofisario , Ruido , Sistema Hipófiso-Suprarrenal , Estrés Fisiológico , Animales , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal/fisiología , Estrés Fisiológico/fisiología , Glucocorticoides/metabolismo , Estrés Psicológico/fisiopatologíaRESUMEN
We studied the features of the functioning of the hypothalamic-pituitary-thyroid (HPT) axis under conditions of constant (4 weeks) lighting (LED lamps intended for office and residential premise) on a translational model of young adult and old female rhesus monkeys, in particular taking into account their behavior. Constant lightning had no significant effect on the levels of thyroid-stimulating hormone, thyroxine, and triiodothyronine under basal conditions in all animals, regardless of age and behavioral characteristics, but induced a decrease in thyroid function under conditions of its activation with thyrotropin-releasing hormone, mainly in old animals.