Neonatal overnutrition programming impairs cholecystokinin effects in adultmale rats.

Overfeeding and rapid weight gain during early life are risk factors for the development of obesity in adulthood. This metabolic malprogramming may be mediated by endocrine disturbances during critical periods of development. Cholecystokinin (CCK) acts on the central nervous system by elevating thermogenesis and the activity of anorectic neurons, modulating overall energy balance. Therefore, we tested the hypothesis that postnatal overfeeding impaired CCK effects. Pups were raised in either a litter of three (neonatal overnutrition/small litter group) or 12 (controls/normal litter group) pups per dam to study the effects of postnatal overfeeding on the central and peripheral CCK systems in adulthood. Rats raised in small litters became overweight during lactation and remained overweight as adults, with increased adiposity and plasma levels of lipids, glucose, insulin, and leptin. Neonatally over-nourished rats showed attenuation of gastric emptying and anorexigenic response to CCK, suggesting that offspring from the SL group may present CCK resistance as adult male rats. Consistent with this idea, overweight rats displayed impaired central response in c-Fos immunoreactivity on the nucleus tractus solitarius, area postrema, paraventricular nucleus, central amygdala, arcuate nucleus, and dorsomedial hypothalamus in response to peripheral CCK at adulthood. The small litter group of adult male rats also exhibited reduced norepinephrine- and CCK-stimulated thermogenesis. Unresponsiveness to the effects of CCK may contribute to overweight and metabolic dysfunctions observed in postnatally over-nourished adult rats. Thus, the involvement of an impaired CCK system, among other neurohormonal failures, may contribute to the development of obesity.

The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging.

We introduce a novel hypothesis which states that the therapeutic utilisation of psilocybin has beneficial effects on genetic aging. Ex hypothesi, we predict a priori that controlled psilocybin interventions exert quantifiable positive impact on leucocyte telomere length (telomeres are a robust predictor of mortality and multifarious aging-related diseases). Our hypothesising follows the Popperian logic of scientific discovery, viz., bold (and refutable) conjectures form the very foundation of scientific progress. The 'psilocybin-telomere hypothesis' is formalised as a logically valid deductive (syllogistic) argument and we provide substantial evidence to support the underlying premises. Impetus for our theorising derives from a plurality of converging empirical sources indicating that psilocybin has persistent beneficial effects on various aspects of mental health (e.g., in the context of depression, anxiety, PTSD, OCD, addiction, etc.). Additional support is based on a large corpus of studies that establish reliable correlations between mental health and telomere attrition (improved mental health is generally correlated with longer telomeres). Another pertinent component of our argument is based on recent studies which demonstrate that "meditative states of consciousness" provide beneficial effects on genetic aging. Similarly, psilocybin can induce states of consciousness that are neurophysiologically and phenomenologically significantly congruent with meditative states. Furthermore, prior research has demonstrated that a single dose of psilocybin can occasion life-changing transformative experiences (≈ 70% of healthy volunteers rate their experience with psilocybin amongst the five personally most meaningful lifetime events, viz., ranked next to giving birth to a child or losing a loved one). We postulate that these profound psychological events leave quantifiable marks at the molecular genetic/epigenetic level. Given the ubiquitous availability and cost effectiveness of telomere length assays, we suggest that quantitative telomere analysis should be regularly included in future psilocybin studies as an adjunctive biological marker (i.e., to facilitate scientific consilience via methodological triangulation). In order to substantiate the 'psilocybin-telomere hypothesis' potential neuropsychopharmacological, endocrinological, and genetic mechanisms of action are discussed (e.g., HPA-axis reactivity, hippocampal neurogenesis, neurotropic growth factors such as BDNF, 5-HT2A receptor agonism, neuroplasticity/synaptoplasticity, brain-wide alterations in neuronal functional connectivity density, involvement of the SLC6A4 serotonin transporter gene, inter alia). The proposed research agenda is thus intrinsically highly interdisciplinary, and it has deep ramifications from a philosophy of science perspective as it connects the epistemic level (qualitative experiential phenomenology) with the ontic level (quantitative molecular genetics) of analysis. In the long term, multidisciplinary and innovative investigations of the 'psilocybin-telomere hypothesis' could contribute to the improvement of senotherapeutic psychological interventions and the identification of novel geroprotective and neuroprotective/restorative pharmaceutical targets to decelerate genetic aging and improve well-being and quality of life during the aging process.

Hypothalamic regulation of headache and migraine.

BACKGROUND: The clinical picture, but also neuroimaging findings, suggested the brainstem and midbrain structures as possible driving or generating structures in migraine. FINDINGS: This has been intensely discussed in the last decades and the advent of modern imaging studies refined the involvement of rostral parts of the pons in acute migraine attacks, but more importantly suggested a predominant role of the hypothalamus and alterations in hypothalamic functional connectivity shortly before the beginning of migraine headaches. This was shown in the NO-triggered and also in the preictal stage of native human migraine attacks. Another headache type that is clinically even more suggestive of hypothalamic involvement is cluster headache, and indeed a structure in close proximity to the hypothalamus has been identified to play a crucial role in attack generation. CONCLUSION: It is very likely that spontaneous oscillations of complex networks involving the hypothalamus, brainstem, and dopaminergic networks lead to changes in susceptibility thresholds that ultimately start but also terminate headache attacks. We will review clinical and neuroscience evidence that puts the hypothalamus in the center of scientific attention when attack generation is discussed.

Prader-Willi syndrome: A model for understanding the ghrelin system.

Subsequent to the discovery of ghrelin as the endogenous ligand of growth hormone secretagogue receptor 1a, this unique gut peptide has been found to exert numerous physiological effects, such as appetite stimulation and lipid accumulation via the central regulating mechanisms in the hypothalamus, stimulation of gastric motility, regulation of glucose metabolism and brown fat thermogenesis, and modulation of stress, anxiety, taste sensation, reward-seeking behaviour and the sleep/wake cycle. Prader-Willi syndrome (PWS) has been described as a unique pathological state characterised by severe obesity and high circulating levels of ghrelin. It was hypothesised that hyperghrelinaemia would explain at least a part of the feeding behaviour and body composition of PWS patients, who are characterised by hyperphagia, an obsession with food and food-seeking, and increased adiposity. Initially, the link between hyperghrelinaemia and growth hormone deficiency, which is observed in 90% of the children with PWS, was not fully understood. Over the years, however, the increasing knowledge on ghrelin, PWS features and the natural history of the disease has led to a more comprehensive description of the abnormal ghrelin system and its role in the pathophysiology of this rare and complex neurodevelopmental genetic disease. In the present study, we (a) present the current view of PWS; (b) explain its natural history, including recent data on the ghrelin system in PWS patients; and (c) discuss the therapeutic approach of modulating the ghrelin system in these patients and the first promising results.

Taurine supplementation in high-fat diet fed male mice attenuates endocrine pancreatic dysfunction in their male offspring.

Obesity in fathers leads to DNA damage and epigenetic changes in sperm that may carry potential risk factors for metabolic diseases to the next generation. Taurine (TAU) supplementation has demonstrated benefits against testicular dysfunction and pancreatic islet impairments induced by obesity, but it is not known if these protective actions prevent the propagation of metabolic disruptions to the next generation; as such, we hypothesized that paternal obesity may increase the probability of endocrine pancreatic dysfunction in offspring, and that this could be prevented by TAU supplementation in male progenitors. To test this, male C57Bl/6 mice were fed on a control diet (CTL) or a high-fat diet (HFD) without or with 5% TAU in their drinking water (CTAU and HTAU) for 4 months. Subsequently, all groups of mice were mated with CTL females, and the F1 offspring were identified as: CTL-F1, CTAU-F1, HFD-F1, and HTAU-F1. HFD-fed mice were normoglycemic, but glucose intolerant and their islets hypersecreted insulin. However, at 90 days of age, HFD-F1 offspring displayed normal glucose homeostasis and adiposity, but reduced glucose-induced insulin release. HFD-F1 islets also exhibited ß- and α-cell hypotrophy, and lower δ-cell number per islet. Paternal TAU supplementation prevented the decrease in glucose-induced insulin secretion and normalized ß-cell size and δ-cell number, and increased α-cell size/islet in HTAU-F1 mice. In conclusion, HFD consumption by male founders decreases ß-cell secretion and islet-cell distribution in their offspring. TAU attenuates the deleterious effects of paternal obesity on insulin secretion and islet-cell morphology in F1 offspring.

Mechanism of electroacupuncture on inflammatory pain: neural-immune-endocrine interactions.

Nociceptive signals are transmitted by peripheral afferents to the central nervous system under pain condition, a process that involves various neurotransmitters and pathways. Electroacupuncture (EA) has been widely used as a pain management technique in clinical practice. Emerging studies have shown that EA can inhibit the induction and transmission of pain signals and, consequently, mediate anti-nociceptive and anti-inflammatory effects by rebalancing the neural-immune-endocrine interactions. This review summarizes the neural-immune-endocrine circuit including peripheral afferent and central efferent, contributing to EA-induced neuroimmune and neuroendocrine modulation in inflammatory pain models. The peripheral afferent circuit includes crosstalk among immune cells, inflammatory cytokines, peripheral nociceptors. In central efferent primarily involves the neuroinflammatory interactions between spinal nociceptive neurons and glial cells. Furthermore, the hypothalamic-pituitary-adrenal axis, sympathetic and vagal nervous may serve as an essential pathway involved in the mechanism of acupuncture-mediated analgesia within the interactions of the central, immune and endocrine systems. Overall, this review focuses on the interactions of neural-immune-endocrine in inflammatory pain, which may be underlying the mechanism of EA-induced anti-inflammatory and antinociceptive effect.

Neural mechanisms of emotion regulation and their role in endocrine and immune functioning: A review with implications for treatment of affective disorders.

In the past century, medical progress has helped increase life expectancy and improve health outcomes more generally. Despite this progress, psychiatric disorders-especially affective disorders including depressive and anxiety disorders-are quite common and have been linked to dysfunction in endocrine and immune systems. In this review, we discuss neurobiological correlates of emotion regulation strategies and their effects on mental and physical health. Some of these correlates, namely sub-regions of prefrontal cortex, also play a key regulatory role in autonomic, endocrine, and immunological processes. Given this functional overlap, we propose a novel neuro-immuno-affective framework that targets improving emotion regulation, in order to: (1) reduce negative affect associated with depressive and/or anxiety disorders; and (2) alter endocrine and immune system functioning (e.g., reduce inflammation)-via changes in activity within (and connectivity between) brain systems that support (successful) emotion regulation. We conclude by arguing that such a framework can be adapted for psychiatric treatment protocols that holistically incorporate neural and immunological biomarkers to promote mental and physical health.

Hypoxic stress: A risk factor for post-concussive hypopituitarism?

Hypopituitarism diagnosed months or years following concussive injury can cause a variety of endocrine disturbances including insufficient secretion of human growth, luteinizing, follicle stimulating, thyroid stimulating, adrenocorticotrophic, and antidiuretic hormones. Recent evidence suggests that autoimmune reactions against pituitary and/or hypothalamic tissue constitute an etiologic factor for this hypopituitarism. One important trigger for autoimmunity is hypoxic stress. This trigger may be especially important in the post-concussive brain, which is particularly vulnerable to hypoxic stress. The vulnerable vasculature of the hypothalamic infundibulum can be a source of local exacerbation of any systemic hypoxia. Taking the above into account, it seems reasonable to hypothesize that hypoxic stress is a risk factor for post-concussive hypopituitarism. Following a discussion of literature relevant to this hypothesis, we suggest retrospective and prospective research methods for testing the hypothesis. Retrospective methods for hypothesis testing include comparing post-concussion victims with and without evidence of hypopituitarism in terms of their history of respiratory problems such as smoking, exposure to indoor and outdoor air pollution, chronic obstructive pulmonary disease, asthma, obstructive sleep apnea, and opioid use or abuse. Significantly greater incidence of respiratory history among the hypopituitarism patients would support the hypothesis. Prospective methods include performing detailed respiratory history and examination immediately post-injury, then performing periodic endocrine panels to detect hypopituitarism during long-term follow up. The hypothesis will be supported if development of hypopituitarism among patients with positive respiratory history or examination findings post-injury is more frequent than hypopituitarism among concussion victims with negative respiratory history and exam findings. If the hypothesis is supported, effective prevention of post-concussive hypopituitarism should include efforts to support optimal respiratory function. Such efforts may be relevant to treatment as well. These efforts would include respiratory therapy, smoking cessation, treatment of obstructive sleep apnea, prudent stepping down of opioid use, incentive spirometry, aerobic exercise, and other conventional measures as indicated. Non-Western measures such as yoga should be considered as well. In addition, chiropractic care as an intervention that may ameliorate hypoxia at the systemic and local levels is discussed.

Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy.

Polycystic ovary syndrome (PCOS) is an endocrine disorder, afflicting females of reproductive age. This syndrome leads to infertility, insulin resistance, obesity, and cardiovascular problems, including a litany of other health issues. PCOS is a polygenic, polyfactorial, systemic, inflammatory, dysregulated steroid state, autoimmune disease, manifesting largely due to lifestyle errors. The advent of biochemical tests and ultrasound scanning has enabled the detection of PCOS in the affected females. Subsequently, a huge amount of insight on PCOS has been garnered in recent times. Interventions like oral contraceptive pills, metformin, and hormone therapy have been developed to bypass or reverse the ill effects of PCOS. However, lifestyle correction to prevent aberrant immune activation and to minimize the exposure to inflammatory agents, appears to be the sustainable therapy of PCOS. This holistic review with multiple hypotheses might facilitate to devise better PCOS management approaches.

Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management.

Since the publication of the Duchenne muscular dystrophy (DMD) care considerations in 2010, multidisciplinary care of this severe, progressive neuromuscular disease has evolved. In conjunction with improved patient survival, a shift to more anticipatory diagnostic and therapeutic strategies has occurred, with a renewed focus on patient quality of life. In 2014, a steering committee of experts from a wide range of disciplines was established to update the 2010 DMD care considerations, with the goal of improving patient care. The new care considerations aim to address the needs of patients with prolonged survival, to provide guidance on advances in assessments and interventions, and to consider the implications of emerging genetic and molecular therapies for DMD. The committee identified 11 topics to be included in the update, eight of which were addressed in the original care considerations. The three new topics are primary care and emergency management, endocrine management, and transitions of care across the lifespan. In part 1 of this three-part update, we present care considerations for diagnosis of DMD and neuromuscular, rehabilitation, endocrine (growth, puberty, and adrenal insufficiency), and gastrointestinal (including nutrition and dysphagia) management.

Psycho-Neuro-Endocrine-Immunology: A Psychobiological Concept.

Psycho-Neuro-Endocrine-Immunology (P.N.E.I.) is a scientific field of study that investigates the link between bidirectional communications among the nervous system, the endocrine system, and the immune system and the correlations of this cross-talk with physical health. The P.N.E.I. innovative medical approach represents a paradigm shift from a strictly biomedical view of health and disease taken as hermetically sealed compartments to a more interdisciplinary one. The key element of P.N.E.I. approach is represented by the concept of bidirectional cross-talk between the psychoneuroendocrine and immune systems. The Low Dose Medicine is one of the most promising approaches able to allow the researchers to design innovative therapeutic strategies for the treatment of skin diseases based on the rebalance of the immune response.

Nutrition, infection and stunting: the roles of deficiencies of individual nutrients and foods, and of inflammation, as determinants of reduced linear growth of children.

The regulation of linear growth by nutritional and inflammatory influences is examined in terms of growth-plate endochondral ossification, in order to better understand stunted growth in children. Linear growth is controlled by complex genetic, physiological, and nutrient-sensitive endocrine/paracrine/autocrine mediated molecular signalling mechanisms, possibly including sleep adequacy through its influence on growth hormone secretion. Inflammation, which accompanies most infections and environmental enteric dysfunction, inhibits endochondral ossification through the action of mediators including proinflammatory cytokines, the activin A-follistatin system, glucocorticoids and fibroblast growth factor 21 (FGF21). In animal models linear growth is particularly sensitive to dietary protein as well as Zn intake, which act through insulin, insulin-like growth factor-1 (IGF-1) and its binding proteins, triiodothyronine, amino acids and Zn2+ to stimulate growth-plate protein and proteoglycan synthesis and cell cycle progression, actions which are blocked by corticosteroids and inflammatory cytokines. Observational human studies indicate stunting to be associated with nutritionally poor, mainly plant-based diets. Intervention studies provide some support for deficiencies of energy, protein, Zn and iodine and for multiple micronutrient deficiencies, at least during pregnancy. Of the animal-source foods, only milk has been specifically and repeatedly shown to exert an important influence on linear growth in both undernourished and well-nourished children. However, inflammation, caused by infections, environmental enteric dysfunction, which may be widespread in the absence of clean water, adequate sanitation and hygiene (WASH), and endogenous inflammation associated with excess adiposity, in each case contributes to stunting, and may explain why nutritional interventions are often unsuccessful. Current interventions to reduce stunting are targeting WASH as well as nutrition.

Early life programming of pain: focus on neuroimmune to endocrine communication.

Chronic pain constitutes a challenge for the scientific community and a significant economic and social cost for modern societies. Given the failure of current drugs to effectively treat chronic pain, which are based on suppressing aberrant neuronal excitability, we propose in this review an integrated approach that views pain not solely originating from neuronal activation but also the result of a complex interaction between the nervous, immune, and endocrine systems. Pain assessment must also extend beyond measures of behavioural responses to noxious stimuli to a more developmentally informed assessment given the significant plasticity of the nociceptive system during the neonatal period. Finally integrating the concept of perinatal programming into the pain management field is a necessary step to develop and target interventions to reduce the suffering associated with chronic pain. We present clinical and animal findings from our laboratory (and others) demonstrating the importance of the microbial and relational environment in programming pain responsiveness later in life via action on hypothalamo-pituitary adrenal (HPA) axis activity, peripheral and central immune system, spinal and supraspinal mechanisms, and the autonomic nervous system.

Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort.

BACKGROUND: Ataxia telangiectasia (AT) is a genetic multisystem disorder, presenting with progressive ataxia, immune deficiency, and propensity toward malignancy. Endocrine abnormalities (growth retardation, reproductive dysfunction, and diabetes) have been described, however detailed information regarding this aspect is lacking. We aimed to characterize endocrine anomalies and growth patterns in a large cohort of AT patients. METHODS: Retrospective study comprising all 52 patients (aged 2-26.2 y) followed at a national AT Clinic. Anthropometric and laboratory measurements were extracted from the charts. RESULTS: Median height-SDS was already subnormal during infancy, remaining negative throughout follow up to adulthood. Height-SDS was more impaired than weight-SDS up to age 4 y, thereafter weight-SDS steadily decreased, resulting in progressively lower BMI-SDS. IGF-I-SDS was low (-1.53 ± 1.54), but did not correlate with height-SDS. Gonadal failure was present in all 13 females older than 10 y but only in one male. Two patients had diabetes and 10 had dyslipidemia. Vitamin D deficiency was observed in 52.2% of the evaluated patients. CONCLUSION: Our results suggest a primary growth abnormality in AT, rather than secondary to nutritional impairment or disease severity. Sex hormone replacement should be considered for female patients. Vitamin D levels should be followed and supplementation given if needed.

[Bardet-Biedl syndrome: cilia and obesity - from genes to integrative approaches]. / Syndrome de Bardet-Biedl: cils et obésité - de la génétique aux approches intégratives.

The primary cilium is a specialized organelle, present at the surface of most eukaryotic cells, whose main function is to detect, integrate and transmit intra- and extra-cellular signals. Its dysfunction usually results in a group of severe clinical manifestations nowadays termed ciliopathies. The latter can be of syndromic nature with multi-organ dysfunctions and can also be associated with a morbid obese phenotype, like it is the case in the iconic ciliopathy, the Bardet Biedl syndrome (BBS). This review will discuss the contribution of the unique context offered by the emblematic BBS for understanding the mechanisms leading to obesity via the involvement of the primary cilium together with identification of novel molecular players and signaling pathways it has helped to highlight. In the current context of translational medicine and system biology, this article will also discuss the potential benefits and challenges posed by these techniques via multi-level approaches to better dissect the underlying mechanisms leading to the complex condition of obesity.

[Effect of steam bath on gastric secretion and some endocrine changes of athlete-fighters].

The issues of adaptation of the gastric glands to thermal load (steam bath) of athlete-fighters. The differences in adaptation to thermal load of gastric glands in connection with a weight category, seniority and age of athletes. Discovered the relationship in reaction to thermal load of gastric and endocrine glands. The stability of steam bath of gastric glands in the middle weight class athlete-fighters combined with the preservation of endocrine homeostasis. The high sensitivity of athlete-fighters of light and middleweight category combined with an authentic increase in serum of blood the concentrations of gastric and aldosterone, and with decrease the concentrations of cortisol.

The endocrine system and sarcopenia: potential therapeutic benefits.

Age related muscle loss, known as sarcopenia, is a major factor in disability, loss of mobility and quality of life in the elderly. There are many proposed mechanisms of age-related muscle loss that include the endocrine system. A variety of hormones regulate growth, development and metabolism throughout the lifespan. Hormone activity may change with age as a result of reduced hormone secretion or decreased tissue responsiveness. This review will focus on the complex interplay between the endocrine system, aging and skeletal muscle and will present possible benefits of therapeutic interventions for sarcopenia.

[Chronic heart failure and cachexia: role of endocrine system]. / Fisiopatologia della cachessia nella insufficienza cardiaca: ruolo del sistema neuroendocrino.

Chronic heart failure (CHF) is a major health problem that carries a devastating prognosis. The prognosis worsens considerably once cardiac cachexia has been diagnosed. Neurohormonal, metabolic, hemodynamic and immunological alterations are involved in the initiation and progression of cardiac cachexia. Cachexia is characterized by a hypothalamic inappropriate response to the mechanisms controlling energy homeostasis. Levels of the anorexigenic hormone leptin are decreased whereas the orexigenic gherlin hormone levels are normal or elevated. Nevertheless, energy intake is not increased as expected due to a persistent activation of the proopiomelanocortin (POMC) system (anorexigenic) paralleled by a decreased activity of the neuropeptide Y (NPY, orexigenic) neurons. Cachexia is also characterized by an imbalance in anabolic (impairment in the growth hormone/insulin-like growth factor-I axis, insulin resistance) and catabolic (increased levels of catecholamines, increased cortisol/dehydroepiandrosterone ratio and activation of proinflammatory cytokines such as tumor necrosis factor-alpha, interleuchin-6, interleuchin-1') at the basis of the wasting process. This review discusses the complex role of the endocrine system in modulating energy balance, appetite and metabolism in patients with chronic heart failure. A joint multidisciplinary effort of the cardiologists, immunologists and endocrinologists might be useful to identify the precise mechanisms involved in the neuroendocrine alteration and to develop therapeutic strategies able to improve the prognosis of CHF patients.

Effects of relaxation on psychobiological wellbeing during pregnancy: a randomized controlled trial.

Prenatal maternal stress is associated with adverse birth outcomes and may be reduced by relaxation exercises. The aim of the present study was to compare the immediate effects of two active and one passive 10-min relaxation technique on perceived and physiological indicators of relaxation. 39 healthy pregnant women recruited at the outpatient department of the University Women's Hospital Basel participated in a randomized controlled trial with an experimental repeated measure design. Participants were assigned to one of two active relaxation techniques, progressive muscle relaxation (PMR) or guided imagery (GI), or a passive relaxation control condition. Self-reported relaxation on a visual analogue scale (VAS) and state anxiety (STAI-S), endocrine parameters indicating hypothalamic-pituitary-adrenal (HPA) axis (cortisol and ACTH) and sympathetic-adrenal-medullary (SAM) system activity (norepinephrine and epinephrine), as well as cardiovascular responses (heart rate, systolic and diastolic blood pressure) were measured at four time points before and after the relaxation exercise. Between group differences showed, that compared to the PMR and control conditions, GI was significantly more effective in enhancing levels of relaxation and together with PMR, GI was associated with a significant decrease in heart rate. Within the groups, passive as well as active relaxation procedures were associated with a decline in endocrine measures except epinephrine. Taken together, these data indicate that different types of relaxation had differential effects on various psychological and biological stress systems. GI was especially effective in inducing self-reported relaxation in pregnant women while at the same time reducing cardiovascular activity.

Clinical observation on the endocrinal and immune functions in subjects with yin-deficiency constitution.

OBJECTIVE: To explore the relationship between yin-deficiency constitution (YDC) and biochemical indexes by way of observing the endocrinal and immune functions in subjects with YDC. METHODS: On the basis of epidemiological investigation, 60 subjects with YDC and 50 with gentle constitution (GC) were selected according to the pertinent criteria. From each subject, 8 mL of fasting venous blood was drawn at 8:00-9:00 in the morning, with the serum separated by centrifugation 3 000 r/min for 5 min and preserved at -70 degrees Celsius in a freezer. Serum levels of corticosterone, cortisol, adrenocorticotrophic hormone (ACTH), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), free triiodothyronine (FT3), free thyroxine (FT4), throtropic stimulation hormone, interleukin 1beta (IL-1beta) and interleukin 2 (IL-2) were detected by double-antibody sandwich ELISA; cAMP/cGMP ratio was calculated, and the difference between the two constitutions in terms of these indexes was analyzed. RESULTS: Serum FT3 was 4.16 + or - 1.38 pmol/L in subjects with YDC, which was higher than that in subjects with GC (3.71 + or - 0.55 pmol/L), but levels of cortisol (124.58 + or - 45.36 ng/mL), ACTH (58.92 + or - 14.55 pg/mL), cGMP (66.00 + or - 18.02 pmol/mL) and FT4 (12.33 + or - 3.12 pmol/L) in YDC were lower than those in GC (13.43 + or - 2.31 pmol/L), showing significant difference (P<0.05). CONCLUSION: YDC is related to some extent with the disturbances in the hypothalamus-pituitary-adrenal axis, hypothalamus-pituitary-thyroid axis, cyclic nucleoside system and immune function.