Long-term effects of early parental loss due to divorce on the HPA axis

We investigated the long-term effects of divorce and early separation from one parent on HPA axis reactivity, in young adults without psychopathology. Participants were 44 young subjects, 22 whose parents divorced before they reached age 10, and 22 controls. Psychiatric symptomatology was measured with the Brief Symptom Inventory (BSI), family perceived stress by the Dyadic Adjustment Scale (DAS), and bonding by the Parental Bonding Instrument (PBI). Assessment of HPA axis function included baseline morning cortisol and ACTH and cortisol response to a CRH stimulation test. No baseline or stimulated group differences were observed for ACTH. Cortisol levels were consistently but insignificantly lower in the divorce group throughout the CRH stimulation reaching statistical significance only at 5 min (p<0.03). Group by time effect reached a trend level (p<0.06). A correlation was found between psychiatric symptomatology and PBI scores; however, both parameters did not correlate with HPA axis activity. A significant correlation was found between DAS scores and ACTH. A regression model revealed a contributing effect for both family stress and child-parent bonding to stimulated ACTH levels. These preliminary findings suggest that even in the absence of adult psychopathology, a history of childhood separation from one parent due to divorce may lead to detectable, albeit mild, long-term alterations in HPA axis activity. Furthermore, they suggest that level of stress at home and parental bonding are important determinants of this effect. It is likely that divorce has significant and sustained effects on children's HPA axis only in the context of a traumatic separation.     

Disentangling psychobiological mechanisms underlying internalizing and externalizing behaviors in youth: longitudinal and concurrent associations with cortisol

Research examining cortisol dysregulation is seemingly contradictory with studies showing that both internalizing and externalizing behaviors are related to high and low cortisol. One extant theory to explain divergent findings in the stress literature is that both hypo- and hyper-arousal of the hypothalamic-pituitary-adrenal (HPA) axis may be present depending on time since onset of the stressor. This theory may extend to the onset of internalizing and externalizing behaviors. Data from 96 youth participating in a longitudinal project were used to examine this possibility. Composite measures of internalizing and externalizing behaviors at both childhood and early adolescence were formed using mother and teacher reports. Multiple salivary cortisol samples were also collected over two consecutive days during early adolescence. Problematic behaviors were associated with cortisol and the direction of the association was dependent on amount of time passed since onset of the behaviors. When examined concurrently in adolescence, youth with more internalizing behaviors had higher morning cortisol; however, when examined longitudinally, youth with more internalizing behaviors in childhood had lower morning cortisol levels as adolescents. Youth with more externalizing behaviors in childhood had flattened diurnal cortisol rhythms as adolescents, and this finding persisted when examined in adolescence. Cortisol dysregulation was greatest in children with the most severe behavior problems. Findings support the theoretical model of blunting of the HPA axis over time. While the HPA axis may show hyper-arousal when youth first display behaviors, long-term exposure may lead to a hypo-arousal of the HPA axis which culminates in a dysregulated diurnal rhythm.     

Validation of urinary cortisol as an indicator of hypothalamic-pituitary-adrenal function in the bearded emperor tamarin (Saguinus imperator subgrisescens)

The use of cortisol levels as a measure of stress is often complicated by the use of invasive techniques that may increase hypothalamic-pituitary-adrenal (HPA) axis activity during sample collection. The goal of this study was to collect samples noninvasively and validate an enzyme-immunoassay (EIA) for the measurement of cortisol in urine to quantify HPA axis activity in the bearded emperor tamarin (Saguinus imperator subgrisescens). Urine samples were collected from trained subjects between 0700 and 0730 hr during a 1-month period, and were pooled for immunological validation. We validated the assay immunologically by demonstrating specificity, accuracy, precision, and sensitivity. For biological validation of the assay, we showed that levels of urinary cortisol (in samples collected between 0700 and 1700 hr) varied significantly across the day. Cortisol concentration was lowest at 0700 hr, increased to a mid-morning peak (0900 hr), and declined across the remainder of the day in a typical mammalian circadian pattern. We thus demonstrate that urinary cortisol can be used to quantify HPA activity in S.i. subgrisescens.     

Changes in Endocrine Orcadian Rhythms as Markers of Physiological and Pathological Brain Aging

We studied the circadian rhythm of plasma melatonin, growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), and Cortisol in 52 mentally healthy old subjects, 35 old demented patients, and 22 clinically healthy young controls. When compared to young controls, the circadian profile of plasma melatonin of old subjects, both demented or not, was clearly flattened, particularly during the night. The selective impairment of nocturnal melatonin secretion was significantly related to both the age and the severity of mental impairment (Mini Mental State Examination [MMSE] score). The PRL and GH circadian profiles were similar in the three groups during the day, but a significant lowering of the values recorded during the night occurred with aging. The impairment of the nocturnal secretion was related to the subjects' age and, for the GH secretory pattern only, also to the MMSE score. The ACTH circadian profile was similar in the three groups studied, even when old subjects exhibited higher ACTH levels throughout the 24h cycle, compared to young controls. Significantly higher Cortisol values at evening- and nighttime occurred in elderly subjects and particularly in the demented group. Both the mean levels and the nadir values of plasma Cortisol were positively related to age and negatively to MMSE score. In order to verify the sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to the steroid feedback, the circadian profile of plasma Cortisol was evaluated also after dexamethasone (DXM) administration (1 mg at 23:00h); the sensitivity of the HPA axis was significantly impaired in old subjects and particularly in the demented ones. These findings suggest that the neuroendocrine alterations already present in physiological aging, due to both anatomical damages and unbalanced central neurotransmitters, are enhanced in senile dementia. (Chronobiology International, 14(4), 385–396, 1997)     

Breeding for robustness: the role of cortisol

Robustness in farm animals was defined by Knap as 'the ability to combine a high production potential with resilience to stressors, allowing for unproblematic expression of a high production potential in a wide variety of environmental conditions'. The importance of robustness-related traits in breeding objectives is progressively increasing towards the production of animals with a high production level in a wide range of climatic conditions and production systems, together with a high level of animal welfare. Current strategies to increase robustness include selection for 'functional traits', such as skeletal and cardiovascular integrity, disease resistance and mortality in various stages. It is also possible to use global evaluation of sensitivity to the environment (e.g. reaction norm analysis or canalization), but these techniques are difficult to implement in practice. The hypothalamic-pituitary-adrenocortical (HPA) axis is the most important stress-responsive neuroendocrine system. Cortisol (or corticosterone) released by the adrenal cortices exerts a large range of effects on metabolism, the immune system, inflammatory processes and brain function, for example. Large individual variations have been described in the HPA axis activity with important physiopathological consequences. In terms of animal production, higher cortisol levels have negative effects on growth rate and feed efficiency and increase the fat/lean ratio of carcasses. On the contrary, cortisol has positive effects on traits related to robustness and adaptation. For instance, newborn survival was shown to be directly related to plasma cortisol levels at birth, resistance to bacteria and parasites are increased in animals selected for a higher HPA axis response to stress, and tolerance to heat stress is better in those animals that are able to mount a strong stress response. Intense selection for lean tissue growth during the last decades has concomitantly reduced cortisol production, which may be responsible for the negative effects of selection on piglet survival. One strategy to improve robustness is to select animals with higher HPA axis activity. Several sources of genetic polymorphism have been described in the HPA axis. Hormone production by the adrenal cortices under stimulation by adrenocorticotropin hormone is a major source of individual differences. Several candidate genes have been identified by genomic studies and are currently under investigation. Bioavailability of hormones as well as receptor and post-receptor mechanisms are also subject to individual variation. Integration of these different sources of genetic variability will allow the development of a model for marker-assisted selection to improve animal robustness without negative side effects on production traits.     

Increased Cortisol Bioavailability,Abdominal Obesity,and the Metabolic Syndrome in Obese Women

Objective: This study was conducted to obtain a detailed profile of hypothalamo‐pituitary‐adrenal (HPA) axis activity and reactivity and its differential relationships with body fat distribution and total fat mass in premenopausal obese women. Research Methods and Procedures: Cortisol responses to stimulation (awakening, food intake, exercise) and suppression (0.25 mg dexamethasone), cortisol metabolism, and tissue sensitivity to glucocorticoids were studied in 53 premenopausal obese women grouped according to their waist‐to hip ratio: women with abdominal body fat distribution (A‐BFD; n = 31) and women with peripheral fat distribution (P‐BFD; n = 22). Results: Comparatively, A‐BFD women had 1) lower awakening salivary cortisol levels; 2) increased salivary responsiveness to a standardized lunch; 3) similar pituitary sensitivity to dexamethasone but decreased sensitivity of monocytes to dexamethasone; 4) similar 24‐hour urinary free cortisol but increased 24‐hour urinary ratio of cortisone‐to‐cortisol; and 5) no difference in corticosteroid binding protein parameters. Discussion: Although abdominal obesity is not very different from generalized obesity in terms of HPA function, subtle variations in HPA axis activity and reactivity are evidenced in A‐BFD premenopausal obese women.     

The hypothalamic-pituitary-adrenal axis and genetic variants affecting its reactivity

The hypothalamic-pituitary-adrenal (HPA) axis plays a primary role in the body response to stresses. Activation of the HPA axis results in the production of corticosteroid hormones that influence a wide variety of body functions, including immunity, metabolism, ion exchange, and behavior. A well-balanced regulation of stress responses is pivotal for maintaining intrabody homeostasis. The HPA axis is regulated at several levels, including stimulatory or inhibitory signals from the brain mediated through neurotransmitter systems and the suppressive feedback influence of corticosteroids themselves. Corticosteroids affect the HPA axis through binding to the glucocorticoid and mineralocorticoid receptors located in the hippocampus. Genes encoding these receptors have several polymorphic regions in which the alleles are associated with different basal and stress-induced levels of hormones secreted in the course of HPS axis stimulation. Additionally, genetic variants of neurotransmitter systems involved in the activation or suppression of the HPA axis have been found. Thus, the given genetic variations are major contributors to the HPA axis-mediated individual resistance or susceptibility to stresses.     

Pigs fed saturated fat/cholesterol have a blunted hypothalamic-pituitary-adrenal function,are insulin resistant and have decreased expression of IRS-1, PGC1α and PPARα

The increasing incidence of insulin resistance has been linked to both increased intake of saturated fatty acids and disruption of the hypothalamic-pituitary-adrenal (HPA) axis. We tested the hypothesis that adding saturated fat/cholesterol to the diet of growing pigs would both disrupt HPA function and cause insulin resistance. Three-month-old pigs were fed either a control (13% energy from fat) or a high saturated fatty acid cholesterol (HSFC) diet (44% energy from fat; 2% cholesterol). After 10 weeks on the diets, intravenous ACTH, insulin and glucose challenges were performed, and after 12 weeks, tissue samples were taken for measurement of mRNA and for lipid-rich aortic lesions. Plasma total, HDL- and LDL-cholesterol were significantly increased in pigs fed the HSFC diet. Cortisol release during the ACTH challenge was suppressed in HSFC-fed pigs which were also more insulin resistant and glucose intolerant than controls. The HSFC diet decreased the expression of insulin receptor (IR) and insulin receptor substrate-1 in muscle and adipose tissue as well as adiponectin and adiponectin receptor 2 expression in fat. The HSFC diet decreased PGC-1α and PPARα expression in muscle but increased PPARα expression in liver. There was a trend for an increase in lipid-stained lesion frequency around the abdominal branches of the aorta in HSFC-fed pigs. We conclude that feeding increased saturated fat to pigs causes disruption in the HPA axis, insulin resistance and decreased muscle and adipose expression of genes controlling insulin signalling and mitochondrial oxidative capacity.     

Detrimental effects of chronic hypothalamic—pituitary—adrenal axis activation

Increasing evidence suggests that the detrimental effects of glucocorticoid (GC) hypersecretion occur by activation of the hypothalamic-pituitary-adrenal (HPA) axis in several human pathologies, including obesity, Alzheimer's disease, AIDS dementia, and depression. The different patterns of response by the HPA axis during chronic activation are an important consideration in selecting an animal model to assess HPA axis function in a particular disorder. This article will discuss how chronic HPA axis activation and GC hypersecretion affect hippocampal function and contribute to the development of obesity. In the brain, the hippocampus has the highest concentration of GC receptors. Chronic stress or corticosterone treatment induces neuropathological alterations, such as dendritic atrophy in hippocampal neurons, which are paralleled by cognitive deficits. Excitatory amino acid (EAA) neurotransmission has been implicated in chronic HPA axis activation. EAAs play a major role in neuroendocrine regulation. Hippocampal dendritic atrophy may involve alterations in EAA transporter function, and decreased EAA transporter function may also contribute to chronic HPA axis activation. Understanding the molecular mechanisms of HPA axis activation will likely advance the development of therapeutic interventions for conditions in which GC levels are chronically elevated.     

Social and reproductive conditions modulate urinary cortisol excretion in black tufted-ear marmosets (Callithrix kuhli)

The links between psychosocial stress, social status, reproductive function, and urinary cortisol were assessed in social groups of black tufted-ear marmosets (Callithrix kuhli). Urinary cortisol excretion was monitored in cases of intrafamily conflict (“sibling fights”) and in daughters in four distinct social contexts: in the family group, while housed singly or in same-sex pairs, and while paired with a male pairmate. Cortisol excretion was elevated in participants in intra-family conflict on the day of and the day following the conflict, relative to concentrations a week prior to or following the conflict. Daughters in natal family groups had concentrations of cortisol that did not differ from reproductively active adult females. This finding held for daughters who were either anovulatory or undergoing ovulatory cycles while in the natal family group. Natal family members and male pairmates exerted buffering effects on levels of activity in the hypothalamic pituitary adrenal axis (HPA) in female C. kuhli. Placing females in solitary housing led to significantly increased cortisol excretion. In the 2 months subsequent to pairing with a male partner, excreted cortisol concentrations in females declined significantly. Daughters removed from their natal family group and housed with a sister did not exhibit increased cortisol levels. These data reveal that activity in the (HPA) axis in marmosets is sensitive to psychosocial stressors, and that urinary cortisol can provide a useful quantitative measure of HPA reactivity. As in other callitrichids, delayed breeding in daughters and reproductive anomalies in C. kuhli appear to be mediated by mechanisms other than elevated HPA activity. Am. J. Primatol. 42:253–267, 1997. © 1997 Wiley-Liss, Inc.     

The hierarchical relationships between the organs of the hypothalamo-hypophyseal-adrenal system (HHAS) in inflammation

The HPA axis is the major system of adaptation to the action of different stressors, including inflammatory agents. The glucocorticoids, the end product of HPA axis prevent the extension of inflammation. In this article we discuss the classic direct and feedback loops in the HPA axis during acute bacterial inflammation. On the basis of literary and own findings we put forward a speculation that different systemic cytokines released one by one during inflammation induce the appearance of new functional relations between the organs of HPA axis. Because of cytokines are involved in the modulation of hormonal sensitivity in the HPA axis the serious modification of direct as well as feedback relations is postulated. On the other hand cytokines and immune cells induce autocrine and paracrine production of cytokines in the HPA axis, that result in autonomization of pituitary and adrenals functions. So, the acute inflammation factors could be seen as "short-time" functional dominants of HPA axis functioning.     

Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat

Cholestatic patients often present with clinical features suggestive of adrenal insufficiency. In the bile duct-ligated (BDL) model of cholestasis, the hypothalamic-pituitary-adrenal (HPA) axis is suppressed. The consequences of this suppression on cholangiocyte proliferation are unknown. We evaluated 1) HPA axis activity in various rat models of cholestasis and 2) effects of HPA axis modulation on cholangiocyte proliferation. Expression of regulatory molecules of the HPA axis was determined after BDL, partial BDL, and α-naphthylisothiocyanate (ANIT) intoxication. The HPA axis was suppressed by inhibition of hypothalamic corticotropin-releasing hormone (CRH) expression by central administration of CRH-specific Vivo-morpholinos or by adrenalectomy. After BDL, the HPA axis was reactivated by 1) central administration of CRH, 2) systemic ACTH treatment, or 3) treatment with cortisol or corticosterone for 7 days postsurgery. There was decreased expression of 1) hypothalamic CRH, 2) pituitary ACTH, and 3) key glucocorticoid synthesis enzymes in the adrenal glands. Serum corticosterone and cortisol remained low after BDL (but not partial BDL) compared with sham surgery and after 2 wk of ANIT feeding. Experimental suppression of the HPA axis increased cholangiocyte proliferation, shown by increased cytokeratin-19- and proliferating cell nuclear antigen-positive cholangiocytes. Conversely, restoration of HPA axis activity inhibited BDL-induced cholangiocyte proliferation. Suppression of the HPA axis is an early event following BDL and induces cholangiocyte proliferation. Knowledge of the role of the HPA axis during cholestasis may lead to development of innovative treatment paradigms for chronic liver disease.     

The Different Roles of Glucocorticoids in the Hippocampus and Hypothalamus in Chronic Stress-Induced HPA Axis Hyperactivity

Hypothalamus-pituitary-adrenal (HPA) hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR) - neuronal nitric oxide synthesis enzyme (nNOS) - nitric oxide (NO) pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can''t induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.     

Maternal influences on epigenetic programming of the developing hypothalamic-pituitary-adrenal axis

Parental and environmental factors during the prenatal and postnatal periods permanently affect the physiology and metabolism of offspring, potentially increasing disease risk later in life. Underlying mechanisms are being elucidated, and effects on a number of organs and metabolic pathways are likely involved. In this review, we consider effects on the developing hypothalamic-pituitary-adrenal (HPA) axis, which may represent a common pathway for developmental programming. The focus is on prenatal and early postnatal development, during which the HPA axis may be programmed in a manner that affects health for a lifetime. Programming of the HPA axis involves, at least in part, epigenetic remodeling of chromatin, leading to alterations in the expression of genes in many organs and tissues involved in HPA activation and response, including the hippocampus and peripheral tissues. Examples of developmental epigenetic modifications affecting the HPA axis as well as target tissues are provided.     

Hypothalamic-pituitary-adrenal axis regulation of inflammation in rheumatoid arthritis

The profound anti-inflammatory effects of glucocorticoids in drug therapy are reflected in the effects in vivo of endogenous glucocorticoids produced by the adrenals. The production of adrenal glucocorticoids is driven by the hypothalamus and pituitary, which in turn are responsive to circulating products of the inflammatory response, especially cytokines. That inflammation can drive the production of anti-inflammatory glucocorticoids denotes the hypothalamic-pituitary-adrenal (HPA)-immune axis as a classic negative feedback control loop. Defects in HPA axis function are implicated in susceptibility to, and severity of, animal models of rheumatoid arthritis (RA), and are hypothesized to contribute to the human disease. In this paper, data supporting the concept of the HPA axis as a regulator of the inflammatory response in animal models of arthritis are reviewed, along with data from studies in humans. Taken together, these data support the hypothesis that the HPA axis provides one of the key mechanisms for inhibitory regulation of the inflammatory response. Manipulation of HPA axis-driven endogenous anti-inflammatory responses may provide new methods for the therapeutic control of inflammatory diseases.     

Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways

There is evidence that immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways play a role in the pathophysiology of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). There is also evidence that these neuroimmune diseases are accompanied by hypothalamic-pituitary-adrenal (HPA) axis hypoactivity as indicated by lowered baseline glucocorticoid levels. This paper aims to review the bidirectional communications between immune-inflammatory and O&NS pathways and HPA axis hypoactivity in ME/CFS, considering two possibilities: (a) Activation of immune-inflammatory pathways is secondary to HPA axis hypofunction via attenuated negative feedback mechanisms, or (b) chronic activated immune-inflammatory and O&NS pathways play a causative role in HPA axis hypoactivity. Electronic databases, i.e., PUBMED, Scopus, and Google Scholar, were used as sources for this narrative review by using keywords CFS, ME, cortisol, ACTH, CRH, HPA axis, glucocorticoid receptor, cytokines, immune, immunity, inflammation, and O&NS. Findings show that activation of immune-inflammatory and O&NS pathways in ME/CFS are probably not secondary to HPA axis hypoactivity and that activation of these pathways may underpin HPA axis hypofunction in ME/CFS. Mechanistic explanations comprise increased levels of tumor necrosis factor-α, T regulatory responses with elevated levels of interleukin-10 and transforming growth factor-β, elevated levels of nitric oxide, and viral/bacterial-mediated mechanisms. HPA axis hypoactivity in ME/CFS is most likely a consequence and not a cause of a wide variety of activated immune-inflammatory and O&NS pathways in that illness.     

Diurnal salivary cortisol is associated with body mass index and waist circumference: The multiethnic study of atherosclerosis

Objective:

Neuroendocrine abnormalities, such as activation of the hypothalamic‐pituitary‐adrenal (HPA) axis, are associated with obesity; however, few large‐scale population‐based studies have examined HPA axis and markers of obesity. We examined the cross‐sectional association of the cortisol awakening response (CAR) and diurnal salivary cortisol curve with obesity.

Design and Methods:

The Multiethnic Study of Atherosclerosis Stress Study includes 1,002 White, Hispanic, and Black men and women (mean age 65 ± 9.8 years) who collected up to 18 salivary cortisol samples over 3 days. Cortisol profiles were modeled using regression spline models that incorporated random parameters for subject‐specific effects. Cortisol curve measures included awakening cortisol, CAR (awakening to 30‐min postawakening), early decline (30 min to 2‐h postawakening), late decline (2‐h postawakening to bedtime), and the corresponding areas under the curve (AUC). Body mass index (BMI) and waist circumference (WC) were used to estimate adiposity.

Results:

For the entire cohort, both BMI and WC were negatively correlated with awakening cortisol (P < 0.05), AUC during awakening rise, and early decline and positively correlated to the early decline slope (P < 0.05) after adjustments for age, race/ethnicity, gender, diabetes status, socioeconomic status, β‐blockers, steroids, hormone replacement therapy, and smoking status. No heterogeneities of effects were observed by gender, age, and race/ethnicity.

Conclusions:

Higher BMI and WC are associated with neuroendocrine dysregulation, which is present in a large population sample, and only partially explained by other covariates.     

Inhibition of Cortisol Secretion by Dexamethasone in Relation to Body Fat Distribution: A Dose-Response Study

In this study, dexamethasone (dex) was administered in random order in doses of 0.05, 0.125, 0.25 and 0.5 mg at 10 p.m. with measurements of serum Cortisol in the morning (8 a.m.) of this and the following day. The test was performed on 22 apparently healthy men, 40 to 60 years of age, recruited from laboratory personnel, outpatient clinics or advertisements in a newspaper. Eight had a body mass index (BMI) (kg/m²) of <25 and 14 of >25. Twelve men had a waist hip ratio (WHR) of <1.0 and 10 men had a WHR of<1.0. Cortisol values at baseline were correlated inversely with WHR and were usually lower in men with a high (>1.0) rather than a low than low (<1.0) WHR after dex inhibition. There was apparently no inhibition by dex at 0.05 and 0.125 mg on average in men with a WHR of >1.0. In addition, the inhibition at 0.5 mg dex correlated negatively with the WHR and was significantly lower (p<0.05) in men with a WHR of >1.0 than in men with a WHR of <1.0. None of these differences or relationships was found to be dependent on BMI. It is concluded that men with an elevated WHR experience a decrease in the inhibition of Cortisol secretion by dex. It is suggested that this could explain or contribute to the elevated sensitivity of their HPA axis. Furthermore, lower morning Cortisol concentrations suggest a change in diurnal secretion patterns.     

Circadian rhythms in rheumatology - a glucocorticoid perspective

The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in regulating and controlling immune responses. Dysfunction of the HPA axis has been implicated in the pathogenesis of rheumatoid arthritis (RA) and other rheumatic diseases. The impact of glucocorticoid (GC) therapy on HPA axis function also remains a matter of concern, particularly for longer treatment duration. Knowledge of circadian rhythms and the influence of GC in rheumatology is important: on the one hand we aim for optimal treatment of the daily undulating inflammatory symptoms, for example morning stiffness and swelling; on the other, we wish to disturb the HPA axis as little as possible. This review describes circadian rhythms in RA and other chronic inflammatory diseases, dysfunction of the HPA axis in RA and other rheumatic diseases and the recent concept of the hepato-hypothalamic-pituitary-adrenal-renal axis, the problem of adrenal suppression by GC therapy and how it can be avoided, and evidence that chronotherapy with modified release prednisone effective at 02:00 a.m. can inhibit proinflammatory sequelae of nocturnal inflammation better compared with GC administration in the morning but does not increase the risk of HPA axis insufficiency in RA.     

Acute and chronic social defeat suppresses humoral immunity of male Syrian hamsters (Mesocricetus auratus).

Stressors, both physical and psychological, can activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to a wide range of physiological responses including increased glucocorticoid release and suppression of immune function. The majority of studies published to date have focused on the effects of physical stressors (e.g., cold exposure, electric shock) on immunity. The present study examined the role of a stressor, social defeat, on humoral immune function of Syrian hamsters (Mesocricetus auratus). Specifically, adult male Syrian hamsters experienced social defeat (i.e., exposure to a dominant animal in that animal's home cage) that was either acute (i.e., a single exposure) or chronic (i.e., daily exposures across 5 days). A control group of animals was placed in a resident's home cage without the resident animal present and did not experience defeat. After the last encounter, blood samples were drawn and animals were subsequently injected with keyhole limpet hemocyanin (KLH). Blood samples were again taken 5 and 10 days postimmunization and serum was analyzed to determine serum cortisol and anti-KLH immunoglobulin G (IgG) concentrations. Cortisol concentrations were elevated in both acutely and chronically defeated hamsters compared with control animals. In contrast, serum IgG concentrations were significantly reduced in both groups of defeated hamsters compared with control animals. Collectively, these results demonstrate that both acute social defeat and chronic social defeat lead to activation of the HPA axis and suppression of humoral immune function. These data suggest that social defeat is an important, ecologically relevant model with which to examine stress-induced immune suppression in rodents.