Plasma Dehydroepiandrosterone Sulfate Levels Research Articles

Pituitary-adrenal axis hormones in early-onset versus late-onset panic disorder

Objective It has been hypothesised that early-onset panic disorder (PD) may constitute a biologically distinct subtype of PD, but the few relevant data are inconclusive. We systematically explored for potential psychopathological and hormonal differences between early-onset (age at onset ≤ 27 years) versus late-onset PD, in consecutively-referred, medication-free, acutely-ill PD outpatients, moreover without comorbid mental disorders except agoraphobia (N = 54; age = 32.3 ± 7.5 years; early-onset = 27; females = 38). Methods Hormones assessed (plasma levels) included adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandrosterone sulphate (DHEAS). Psychopathological measures included panic attacks’ number during last three weeks, the Agoraphobic Cognitions and the Body Sensations Questionnaires and the Hamilton Anxiety Rating Scale. Results Early-onset PD patients – compared to their late-onset counterparts – had longer duration of the disease. The two onset-groups demonstrated similar panic and anxiety symptoms and similar ratios of smokers/never-smokers. However, early-onset patients demonstrated significantly greater ACTH and DHEAS levels and higher (marginally significant) cortisol levels than the late-onset patients. Moreover, in the early-onset patients only, significant positive correlations emerged between ACTH levels and the severity of both panic and anxiety symptomatology. Conclusions These findings suggest that the two onset-groups demonstrate significant differences in the hypothalamic-pituitary-adrenal axis functioning, at least when acutely-ill. Key points Early-onset panic disorder (EOPD) may differ biologically from late-onset PD (LOPD). EOPD was correlated with greater adrenocorticotropic hormone (ACTH) plasma levels. EOPD was correlated with greater dehydroepiandrosterone sulphate plasma levels. In EOPD only, ACTH levels were positively correlated with panic and anxiety symptoms.

The impact of atorvastatin on cardiometabolic risk factors in brothers of women with polycystic ovary syndrome

BackgroundWomen with polycystic ovary syndrome (PCOS) are characterized by increased cardiometabolic risk. The aim of the current study was to compare the impact of atorvastatin on plasma levels of cardiometabolic risk factors between men whose sisters had either PCOS or were unaffected.MethodsThe study population consisted of two age-, fat-free mass index-, blood pressure- and plasma lipid-matched groups of men with elevated total and LDL cholesterol levels: 20 brothers of PCOS probands (group 1) and 20 brothers of healthy women (group 2). Both groups were then treated with atorvastatin (40 mg daily) for the following 6 months. At the beginning and at the end of the study, we assessed plasma lipid levels, glucose homeostasis markers and levels of dehydroepiandrosterone sulfate, testosterone, bioavailable testosterone, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen and 25-hydroxyvitamin D.ResultsAt the beginning of the study, both treatment arms differed in the degree of insulin resistance, calculated bioavailable testosterone, as well as in plasma levels of dehydroepiandrosterone sulfate, uric acid, hsCRP and 25-hydroxyvitamin D. Although atorvastatin reduced total and LDL cholesterol levels, this effect was stronger in group 2 than group 1. In group 2, atorvastatin exerted also a more potent impact on hsCRP, fibrinogen and homocysteine. An unfavorable impact on insulin sensitivity was observed only in group 1; while, statistically significant changes in uric acid and 25-hydroxyvitamin D levels were found only in group 2.ConclusionThe obtained results suggest that cardiometabolic effects of atorvastatin are less pronounced in male siblings of PCOS probands than in brothers of unaffected women.

In vitro modulatory effect of dehydroepiandrosterone sulfate on apoptosis and expression of apoptosis-related genes in patients with systemic lupus erythematosus.

Systemic lupus erythematosus‌ (SLE) is an autoimmune disease characterized by hyperactive B cells that produce various autoantibodies. Sex hormones have been documented to influence the development of SLE, in which women with SLE have low plasma level of dehydroepiandrosterone sulfate (DHEAS). A strong conclusion about the effect of DHEAS on apoptosis in SLE patients has not been provided. The aim of this study was to assess apoptotic effects of DHEAS on peripheral blood lymphocytes (PBLs) from SLE patients. Twenty SLE patients and 20 age- and sex-matched healthy controls were included into this study. Concentration of DHEAS was measured using enzyme-linked immunosorbent assay in serum from all participants. Freshly isolated PBLs from each individual were treated with 7.5-µmol of DHEAS for 24 hr in cell culture medium to assess the effect of DHEAS on apoptosis using fluorescein isothiocyante-conjugated annexin V and propidium iodide. The messenger RNA (mRNA) expression level of apoptosis-related genes (Fas, Fas-L, Bcl-2, and Bax) in PBLs was measured using real-time PCR before and after treating with DHEAS. Level of DHEAS was low in SLE patients compared with healthy controls (p < 0.05). After treating with DHEAS, the percentage of apoptotic cells in SLE patients was decreased in comparison with healthy controls. DHEAS treatment increased the mRNA expression level of Bcl-2 in PBLs from SLE patients. DHEAS reduced the apoptosis rate in PBLs from SLE patients and may decrease the load of autoantigens. Therefore, DHEAS might be considered as a therapeutic tool in SLE patients.

Developmental Programming of Capuchin Monkey Adrenal Dysfunction by Gestational Chronodisruption.

In the capuchin monkey (Cebus apella), a new-world nonhuman primate, maternal exposure to constant light during last third of gestation induces precocious maturation of the fetal adrenal and increased plasma cortisol in the newborn. Here, we further explored the effects of this challenge on the developmental programming of adrenal function in newborn and infant capuchin monkeys. We measured (i) plasma dehydroepiandrosterone sulphate (DHAS) and cortisol response to ACTH in infants with suppressed endogenous ACTH, (ii) plasma DHAS and cortisol response to ACTH in vitro, and (iii) adrenal weight and expression level of key factors in steroid synthesis (StAR and 3β-HSD). In one-month-old infants from mothers subjected to constant light, plasma levels of cortisol and cortisol response to ACTH were twofold higher, whereas plasma levels of DHAS and DHAS response to ACTH were markedly reduced, compared to control conditions. At 10 months of age, DHAS levels were still lower but closer to control animals, whereas cortisol response to ACTH was similar in both experimental groups. A compensatory response was detected at the adrenal level, consisting of a 30% increase in adrenal weight and about 50% reduction of both StAR and 3β-HSD mRNA and protein expression and the magnitude of DHAS and cortisol response to ACTH in vitro. Hence, at birth and at 10 months of age, there were differential effects in DHAS, cortisol production, and their response to ACTH. However, by 10 months of age, these subsided, leading to a normal cortisol response to ACTH. These compensatory mechanisms may help to overcome the adrenal alterations induced during pregnancy to restore normal cortisol concentrations in the growing infant.

Reversion of aging-related DHEAS decline in mouse plasma alleviates aging-related glucose tolerance impairment by potentiation of glucose-stimulated insulin secretion of acute phase

Aims/hypothesisThe latest research proposes mild age-related diabetes (MARD) as a subgroup of type 2 diabetes. While in human circulating dehydroepiandrosterone sulfate (DHEAS) decline with age is related to MARD, the role of circulating DHEAS in insulin secretion remains little known. MethodsAfter intraperitoneal administration of glucose (2 g/kg) together with DHEAS (50 μg/kg) or equivalent DMSO to young (6–8 week old) or aging (12 month old) male C57BL/6 mice, plasma DHEAS and blood glucose were measured at indicated time point. Then in vitro, we investigated DHEAS effects on GSIS of acute phase in aging mice pancreatic islets as well as in MIN6 cells. Finally we conducted pharmacological studies in MIN6 cells to examine whether exert its effects on insulin secretion by itself. ResultsWe found in vivo that aging mice had lower plasma DHEAS levels and impaired glucose tolerence compared to young mice and that the aged mice but not the young mice receiving DHEAS supplement had improved glucose tolerance as soon as 15 min after glucose injection compared to the ones with DMSO administration. These results indicate that in male mice, aging-related DHEAS decline in plasma contribute to aging-related impairment of glucose tolerence and that reversion of aging-related DHEAS deficiency in aging mice plasma could alleviate aging-related glucose tolerance impairment. Consistently, in vitro DHEAS glucose-and dose-dependently potentiated glucose-stimulated insulin secretion (GSIS) of acute phase in both aging male mice pancreatic islets and MIN6 cells. Moreover, none of steroid sulfatase (STS) inhibitor STX64 (10 nM), androgen receptor (AR) blocker flutamide (1 mM) or estrogen receptor (ER) antagonist ICI182780 (1 mM), affected DHEAS-potentiated high GSIS of acute phase indicating this potentiation exercised by DHEAS per se Conclusions/interpretation These results lead us to tentatively conclude that aging-related DHEAS decline may imply MARD development and that adequate DHEAS supplement may be a precise medicine and preventive measure for MARD.

Bioanalytical LC-MS Method for the Quantification of Plasma Androgens and Androgen Glucuronides in Breast Cancer.

The physiological and pathological development of the breast is strongly affected by the hormonal milieu consisting of steroid hormones. Mass spectrometry (MS) technologies of high sensitivity and specificity enable the quantification of androgens and consequently the characterization of the hormonal status. The aim of this study is the assessment of plasma androgens and androgen glucuronides, in the par excellence hormone-sensitive tissue of the breast, through the application of liquid chromatography-mass spectrometry (LC-MS). A simple and efficient fit-for-purpose method for the simultaneous identification and quantification of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), androsterone glucuronide (ADTG) and androstane-3α, 17β-diol-17-glucuronide (3α-diol-17G) in human plasma was developed and validated. The presented method permits omission of derivatization, requires a single solid-phase extraction procedure and the chromatographic separation can be achieved on a single C18 analytical column, for all four analytes. The validated method was successfully applied for the analysis of 191 human plasma samples from postmenopausal women with benign breast disease (BBD), lobular neoplasia (LN), ductal carcinoma in situ and invasive ductal carcinoma (IDC). DHEAS plasma levels exhibited significant differences between LN, IDC and BBD patients (P < 0.05). Additionally, ADTG levels were significantly higher in patients with LN compared with those with BBD (P < 0.05).

Lack of specific association between panicogenic properties of caffeine and HPA-axis activation. A placebo-controlled study of caffeine challenge in patients with panic disorder

A subgroup of patients with Panic Disorder (PD) exhibits increased sensitivity to caffeine administration. However, the association between caffeine-induced panic attacks and post-caffeine hypothalamic–pituitary–adrenal (HPA)-axis activation in PD patients remains unclear. In a randomized, double-blind, cross-over experiment, 19 PD patients underwent a 400-mg caffeine-challenge and a placebo-challenge, both administered in the form of instant coffee. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed at both baseline and post-challenge. No patient panicked after placebo-challenge, while nine patients (47.3%) panicked after caffeine-challenge. Placebo administration did not result in any significant change in hormones' plasma levels. Overall, sample's patients demonstrated significant increases in ACTH, cortisol, and DHEAS plasma levels after caffeine administration. However, post-caffeine panickers and non-panickers did not differ with respect to the magnitude of the increases. Our results indicate that in PD patients, caffeine-induced panic attacks are not specifically associated with HPA-axis activation, as this is reflected in post-caffeine increases in ACTH, cortisol and DHEAS plasma levels, suggesting that caffeine-induced panic attacks in PD patients are not specifically mediated by the biological processes underlying fear or stress. More generally, our results add to the evidence that HPA-axis activation is not a specific characteristic of panic.

Endogenous levels of circulating androgens and risk of Crohn's disease and ulcerative colitis among women: a nested case-control study from the nurses' health study cohorts.

Androgens, which are known to be altered by exogenous hormone use, have recently been linked to alterations of the gut microbiome and mucosal immune function. No study has evaluated the association between circulating levels of androgens and risk of Crohn's disease (CD) and ulcerative colitis (UC). We conducted a nested case-control study of women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided a blood specimen. Cases of CD and UC were each matched to 2 controls. Prediagnosis plasma levels of dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin were measured. We examined the association of each analyte with risk of CD or UC using conditional logistic regression models. Compared with women in the lowest quintile of testosterone, the multivariable-adjusted odds ratios for CD were 0.86 (95% confidence interval, 0.39-1.90) for women in the second quintile, 0.49 (95% confidence interval, 0.21-1.15) for the third quartile, 0.22 (0.08-0.65) for the fourth quintile, and 0.39 (95% confidence interval, 0.16-0.99) for the highest quintile (Plinear trend = 0.004). In contrast, we did not observe a consistent association between prediagnostic testosterone and risk of UC (Plinear trend = 0.84). We also did not observe any association between plasma levels of sex hormone-binding globulin or dehydroepiandrosterone sulfate and risk of UC or CD (all Plinear trends > 0.10). Among women, prediagnostic circulating testosterone is associated with a lower risk of CD but not UC. Further studies to understand the biological mechanisms by which endogenous androgens may mediate the etiopathogenesis of CD are warranted.

Investigation of dermatology life quality index and serum prolactin and serum dehydroepiandrosterone sulphate levels in patients with chronic urticaria.

Chronic urticaria (CU) is known to be one of the most disturbing diseases which significantly affect the quality of life. Prolactin (PRL) and DHEA-S (dehydroepiandrosterone sulfate) are stress-associated hormones in chronic urticaria. In the present study, we measured DHEA-S and prolactin levels of CU patients, compared them with healthy subjects and evaluated the association between disease status and serum levels. Plasma DHEA-S and serum PRL concentrations were measured in 48 CU patients and 31 healthy subjects. CU activity was assessed with the use of the symptom scores recommended with EAACI/GALEN/EDF guidelines. All the patients participating in this study were evaluated by means of Dermatology Life Quality Index (DLQI). With respect to DLQI and clinical activity scores, plasma DHEA-S and serum prolactin levels were compared. Median plasma concentration of DHEA-S was significantly lower in CU patients as compared with healthy subjects (p = 0.026). DHEA-S levels of females were significantly lower than males (p = 0.001). Mean PRL values of the patients were higher than the controls, but not statistically significant (p = 0.619) and there was a statistically signifcant inverse correlation with DHEA-S levels (p = 0.04, r = -0.298). Therewas a significant correlation between DLQI and clinical disease activity (p < 0.001, r = 0.748). The exact relation of hormones to CU pathogenesis remains to be determined by further clinical studies. In addition, therapies aiming to increase DHEA-S and decrease PRL may be subject to trial in CU.

Androgen Supplementation During Aging: Development of a Physiologically Appropriate Protocol

Men show an age-related decline in the circulating levels of testosterone (T) and dehydroepiandrosterone sulfate (DHEAS). Consequently, there is interest in developing androgen supplementation paradigms for old men that replicate the hormone profiles of young adults. In the present study, we used old (21-26 years old) male rhesus monkeys as a model to examine the efficacy of an androgen supplementation paradigm that comprised oral T administration (12 mg/kg body weight, dissolved in sesame oil/chocolate) in the evening, and two oral DHEA administrations, 3 hr apart (0.04 mg/kg body weight, dissolved in sesame oil/chocolate) in the morning. After 5 days of repeated hormone supplementation, serial blood samples were remotely collected from each animal hourly across the 24-hr day, and assayed for cortisol, DHEAS, T, 5α-dihydrotestosterone (DHT), estrone (E1), and 17β-estradiol (E2). Following androgen supplementation, T levels were significantly elevated and this was associated with a more sustained nocturnal elevation of T's primary bioactive metabolites, DHT and E1 and E2. Plasma DHEAS levels were also significantly elevated after androgen supplementation; DHEAS levels rose in the early morning and gradually declined during the course of the day, closely mimicking the profiles observed in young adults (7-12 years old); in contrast, cortisol levels were unaltered by the supplementation. Together the data demonstrate a non-invasive androgen supplementation paradigm that restores youthful circulating androgen levels in old male primates. Because this paradigm preserves the natural circulating circadian hormone patterns, we predict that it will produce fewer adverse side effects, such as perturbed sleep or cognitive impairment.

Plasma dehydroepiandrosterone sulfate levels in patients with major depressive disorder correlate with remission during treatment with antidepressants.

We attempted to investigate whether dehydroepiandrosterone sulfate (DHEA-S) levels are associated with remission of major depressive disorder by assessing scores on the 17-Item Structured Interview Guide for the Hamilton Depression before and after antidepressant treatment. Plasma DHEA-S levels in 24 patients diagnosed with major depressive disorder on the basis of Diagnostic and Statistical Manual of Mental Disorders, fourth edition (text revision) before and after antidepressant treatment, and 24 healthy, gender-matched, and age-matched controls were measured using a radioimmunoassay kit. Plasma DHEA-S levels in patients were significantly higher than those in healthy controls. In patients who achieved remission after antidepressant treatment, plasma DHEA-S levels significantly declined compared with the levels before treatment. A significant correlation was observed between changes in DHEA-S levels and Absence of Depressive and Anxious Mood scores, which are calculated from the 2-Item Structured Interview Guide for the Hamilton Depression rating as follows: severity of depressive mood and anxiety in patients before and after antidepressant treatment. These findings suggest that plasma DHEA-S levels can be used as a putative indicator of the state of remission in patients with major depressive disorder. Copyright © 2014 John Wiley & Sons, Ltd.

Relation between dehydroepiandrosterone sulfate (DHEA-S) and success of labour induction in prolonged gestation

To evaluate the relationship between maternal Dehydroepiandrosterone sulphate (DHEA-S) and success of labour induction in prolonged gestation. Fifty (50) women with a prolonged pregnancy > 41 weeks were included in the prospective study. After full history, examination, Bishop's score was recorded by two observers, followed by ultrasound scan and cardiotocography (CTG) to assess foetal condition. Ten (10) mL of venous blood was taken for measuring plasma DHEA-S level before induction of labour. Induction of labour was carried out by Misoprostol 25 μg vaginal suppository every 4 hours for 6 doses maximally. Patients in the first, second and third stages of labour were managed according to Ain Shams University Maternity Hospital protocol. The outcome measures, success of labour induction, relation between both DHEA-S and Bishop's score and the success of labour induction. In this study, there was no significant difference between the group of failed induction and group of successful induction regarding the mean age, mean body mass index (BMI), mean parity, mean birth weight, and mean Apgar score at 5 minutes. The mean serum DHEA-S was significantly higher in successful induction group compared to failed induction group (108.2±10.3 versus 44.7±18.3 µg/dL) and the mean Bishop's score was also significantly higher in successful induction group compared to failed induction group (7.3±1.0 versus 4.5±0.5), ( P <0.001). In this study, there was significant direct correlation between serum DHEA-S and Bishop's score, the higher DHEA-S is related to higher Bishop's score ( r =0.785; P <0.001). Using ROC curve, the serum DHEA-S at cutoff level 90.6 μg/dL was a predictor of successful labour induction with 97.2% sensitivity and 92.3% specificity. Pre-induction serum DHEA-S assay can be used beside clinical assessment and Bishop's score to anticipate successful induction of labour in prolonged gestation.

Inhibition of dehydroepiandosterone sulfate action in androgen-sensitive tissues by EM-1913, an inhibitor of steroid sulfatase

Steroid sulfatase (STS) plays an important role in the formation of estrogens and androgens by allowing the conversion of inactive circulating sulfated steroids into active hormones. These steroids support the development and growth of a number of hormone-dependent cancers, including prostate cancer. Here, we tested a non-estrogenic and non-androgenic inhibitor of steroid STS, namely EM-1913, with special attention to its potential use in the treatment of prostate cancer. After determining the required dosage of dehydroepiandrosterone sulfate (DHEAS) needed to stimulate the ventral prostate and seminal vesicles in castrated rats, we measured that EM-1913 partially (26%) and almost entirely blocked (81%) the stimulating effect of DHEAS on ventral prostates and seminal vesicles, respectively. In addition, the homogenization of these two tissues allowed us to confirm that they were completely deprived of STS activity following a treatment with EM-1913. This effect is also reflected in blood, since the plasma level of DHEAS was increased in animals treated with EM-1913, whereas the levels of dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT), two DHEAS metabolites, meanwhile decreased. From these results, we concluded that STS inhibitor EM-1913 is a good candidate for additional preclinical studies.

Low plasma DHEA-S increases mortality risk among male hemodialysis patients

ObjectiveThe incidence of chronic kidney disease (CKD) is on the rise. CKD patients are at high risk of cardiovascular (CVD) and all-cause mortality. CKD patients have several endocrine disorders, including low levels of dehydroepiandrosterone sulfate (DHEA-S). In the general population, low levels of DHEA-S are associated with high CVD and all-cause mortality. The aim of this study was to analyze the prognostic value of plasma DHEA-S on the survival of CKD patients on hemodialysis. MethodThis was a single-center prospective cohort study on two hundred CKD patients on hemodialysis, which assessed the prognostic value of plasma DHEA-S on their survival. ResultWe found that plasma DHEA-S levels were negatively associated with age, and positively associated with dialysis duration and plasma creatinine, albumin, and phosphate levels in hemodialysis men. Elderly patients with co-morbidities (i.e. diabetes mellitus, congestive heart failure, and chronic obstructive pulmonary disease), poorer fluid control which was evaluated by higher cardiothoracic ratio, and low plasma creatinine and albumin levels seemed to have poor prognosis in hemodialysis men. Furthermore, low plasma DHEA-S levels were significantly associated with CVD-related [hazard ratio (HR)=3.877; P=0.021], non-CVD-related (HR=3.522; P=0.016), and all-cause mortality (HR=3.667; P=0.001) in hemodialysis men. But low plasma DHEA-S levels were not significantly associated with CVD-related, non-CVD-related, and all-cause mortality in hemodialysis women. Multivariate Cox regression analysis suggested that low plasma DHEA-S levels are significantly and independently associated with all-cause mortality in hemodialysis men (HR=2.933; P=0.033). ConclusionThe study suggested that low plasma DHEA-S was independently and significantly associated with all-cause mortality in CKD hemodialysis men.

Plasma dehydroepiandrosterone sulphate and insulin‐like growth factor I levels in obstructive sleep apnoea syndrome

We aimed to assess whether obstructive sleep apnoea syndrome (OSAS) affects plasma IGF-1 and dehydroepiandrosterone sulphate (DHEA-S) levels in men, factors implicated in the development of age-related metabolic disorders. We conducted a cross-sectional and longitudinal clinical study. We measured plasma IGF-1 and DHEA-S levels in 191 non-drug-treated Japanese men (34 primary snorers (PS), 88 patients with mild-to-moderate OSAS and 69 patients severe OSAS ). Plasma IGF-1 and DHEA-S were negatively correlated with age. Plasma IGF-1 was also negatively correlated with plasma glucose, HOMA-IR and systolic blood pressure and apnoea parameters such as the apnoea-hypopnea index, minimum oxygen saturation and slow-wave sleep (SWS) time. Plasma DHEA-S was associated with plasma glucose, HbA1c and free fatty acid and was negatively correlated with SWS time. To eliminate the influence of age, PS, patients with mild-to-moderate OSAS and severe OSAS were divided into three groups by age: young (<40 years), middle-aged (40-59 years) and elderly (≥ 60 years). Patients with severe OSAS aged <40 or <60 years had lower plasma IGF-1 or DHEA-S levels, respectively, than did the corresponding snorers and mild-to-moderate OSAS groups. Continuous positive airway pressure therapy for generally 16-18 months increased plasma IGF-1 levels in patients with severe OSAS aged <40 years (n = 18). Plasma DHEA-S levels were increased in patients with severe OSAS aged <60 years, whose DHEA-S level was below the mean value for that age (n = 23/41). Severe OSAS could reduce plasma IGF-1 and DHEA-S levels in younger, but not elderly Japanese men, which is potentially associated with the development of metabolic abnormalities.

Individual patterns in aging: monkey's lessons

Recent research on rhesus monkeys suggest that the effects of calorie restriction in nonhuman primates recapitulate many of the physiological, hematological, hormonal, immunological, and biochemical effects produced in rodents [1,2]. Measurments of markers of age-related diseases such as diabetes, cardiovascular disease, and possibly cancer suggest that restricted monkeys are healthier than ad libitum counterparts [3]. Thus, studies in monkeys are very important for identification and characterization of candidate biomarkers of aging. At least one biomarker, the rate of decrease in plasma dehydroepiandrosterone (DHEA), suggests that calorie restricted monkeys may be aging slowly [3]. The intrinsic factors, contributing to decreased stress adaptability in old animals, namely disturbances of the hypothalamic-pituitary-adrenal (HPA) axis, are likely to be responsible, at least in part, for health deterioration in the aged [4,5]. At the same time it is well known that the heterogeneity is crucial feature of the aging process. There are individual peculiarities in vulnerability and resistance to stresses and stress-related pathologies among different persons due to the heterogeneity of the ageing process. It is of great importance to elucidate the individual specificity of age-related changes of the HPA axis in the context of aging of the organism as a whole and the stress-dependent age pathologies. A paper by Goncharova and colleagues from Research Institute of Medical Primatology at Sochi, Russia [6] renders further support to this important issue and indicate a number of highly relevant points that will have to be taken into consideration for a better understanding of mechanisms involved and possible extrapolations to the situation in humans. Their aim was see in which way the differences in the HPA axis function in young (6-8 years) and old (20-27 years) female rhesus monkeys depends on various behavioral types, under basal conditions, as well as under conditions of acute psycho-emotional stress. It has been found that the monkeys with depression-like behavior demonstrate age-related changes in the HPA axis function, accompanied by maximal absolute and relative hypercortisolemia under basal conditions as well as under stress. The authors have also found that young aggressive monkeys, in comparison with young monkeys of other behavior groups, demonstrated the highest plasma levels of DHEA sulfate and the lowest molar ratios between cortisol and DHEA sulfate. No such differences were observed between old aggressive animals and other behavioral groups. The least pronounced age-related changes in the HPA axis have been revealed for the monkeys with average behavior. Goncharova and colleagues have found, for the first time, that monkeys with depression-like behavior demonstrate age-related changes in HPA axis function that are accompanied by maximal absolute and relative hypercortisolemia under basal conditions, as well as by a significantly greater increase in plasma cortisol levels under acute stress. It worthy to note that taken together these results suggest that age-related dysfunctions of the HPA axis are individual features associated with peculiarities of adaptive behavior of animals. This approach seems very fruitful for future studies. Indeed, nonhuman primates and humans are in physiology of HPA: both species have cortisol as a main glucocorticoid hormone, similar circadian rhythm of HPA activity, age-related decline in DNEA sulfate secretion [7-9]. Furthermore, unlike rodents, nonhuman primates feature the psycho-emotional reactions and adaptive behavior more similar to those in humans. Thus, Goncharova and colleagues studies focused on basic and complex issues which are important for better understanding of individual peculiarities of human aging.

Aging of the hypothalamic-pituitary-adrenal axis in nonhuman primates with depression-like and aggressive behavior

We have investigated aging of the hypothalamic-pituitary-adrenal (HPA) axis in female rhesus monkeys that differ in adaptive behavior. Plasma cortisol (F) and dehydroepiandrosterone sulfate (DHEA-S) concentrations under basal conditions and under acute psycho-emotional stress were evaluated in blood plasma of young (6-8 years) and old (20-27 years) female rhesus monkeys with various types of adaptive behavior (aggressive, depression-like, and average). We have found that the age-related changes in the HPA axis of monkeys with depression-like behavior were accompanied by the maximal absolute and relative hypercortisolemia under both basal conditions and stress. Moreover, young aggressive monkeys, in comparison with young monkeys of other behavior groups, demonstrated the highest plasma levels of DHEA-S and the lowest molar ratios between F and DHEA-S. Thus, age-related dysfunctions of the HPA axis are associated with adaptive behavior of animals.

Plasma estrone sulfate assay in men: Comparison of radioimmunoassay, mass spectrometry coupled to gas chromatography (GC–MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS)

Background Estrogens are involved in the natural history of the prostate cancer and estrone sulfate, the quantitatively main circulating plasma estrogen in men, has been associated with an aggressive form of this cancer. A convenient and accurate plasma assay of this steroid has become important. Methods We simultaneously assayed estrone sulfate in the plasma of one hundred men aged 30–50 years, according to LC-MS/MS, GC–MS after solvolysis of E 1S, radioimmunoassay after a chromatographic purification step, and a direct RIA commercial kit. Results Estrone sulfate plasma levels obtained with the first three methods were not significantly different. However, estrone sulfate levels measured by the direct RIA were three-fold higher than those obtained by the first three methods. We showed that the excessively high estrone sulfate levels obtained with the direct RIA kit had two origins: interference by high dehydroepiandrosterone sulfate plasma levels in men, and estrone sulfate inaccurate low concentrations in the standards. Conclusion The LC-MS/MS method can be considered as an optimum option for clinical laboratory. The GC–MS method requires solvolysis to estrone, but allows simultaneous unconjugated steroid measurement. RIA method, with chromatographic purification, is cumbersome, but less expensive. DSL-5400 kit yielded estrone sulfate plasma levels that were too high.

Hypothalamic serotonin-1A receptor binding measured by PET predicts the plasma level of dehydroepiandrosterone sulfate in healthy women

Serotonin modulates the activity of the hypothalamic–pituitary–adrenal (HPA) axis particularly via the serotonin-1A receptor (5-HT 1A). Therefore, the rationale of this positron emission tomography (PET) study was to investigate the influence of the 5-HT 1A receptor distribution in the human brain on plasma levels of dehydroepiandrosterone sulfate (DHEAS) and cortisol in vivo. Eighteen healthy female were measured with PET and the selective 5-HT 1A receptor radioligand [carbonyl- 11C]WAY-100635. Nine a priori defined brain regions (hypothalamus, orbitofrontal cortex, amygdala, hippocampus, anterior and posterior cingulate cortices, dorsal raphe nucleus, retrosplenial cortex, and insula) and the cerebellum (reference region) were delineated on coregistered MR images. DHEAS and cortisol plasma levels were collected by blood sampling in the morning of the PET day. Linear regression analysis of DHEAS plasma level as dependent variable and hypothalamic 5-HT 1A receptor binding potential (BP) as independent variable showed a highly significant association ( r = .691, p = .002). The hypothalamic 5-HT 1A BP predicted 47.7% of the variability in DHEAS plasma levels. Regressions were borderline significant ( p < .01, Bonferroni corrected threshold <.0056) between 5-HT 1A BP in the anterior cingulate and orbitofrontal cortices and free cortisol levels. No significant associations between DHEAS or cortisol and the 5-HT 1A receptor BP in other investigated brain regions were found. In conclusion, the serotonergic system may influence the DHEAS plasma level by modulating CRH and ACTH release via hypothalamic 5-HT 1A receptors as reported for cortisol before. As disturbances of the HPA axis as well as changes of the 5-HT 1A receptor distribution have been reported in affective disorders, future studies should focus on these interactions.

P03-345 Levels of plasma serum dehydroisoandrosterone-sulfate and cortisol in combat veterans

ObjectivesRecent studies suggest that such neuroactive steroids as dehydroepiandrosterone-sulfate (DHEAS) and cortisol play an important part in conditioning psychiatric disorders in combatants. Cortisol may have a neurotoxic effect whereas DHEAS can produce a neuroprotective impact.MethodWe have investigated the morning plasma level of DHEAS and cortisol as well as DHEAS/cortisol ratio in the group of forty combat veterans in the remote period of combat stress and the same parameters - in the control group consisting of 30 healthy males (N=30).ResultsIn comparison with the control group, the combatants reliably showed considerably higher level of cortisol (p&lt; 0,05), lower level of DHEAS (p&lt; 0,001) and lower DHEAS/cortisol ratio (p&lt; 0,001). Then the veterans were divided into two groups with the help of the “Mississippi Scale for Combat-Related Posttraumatic Stress Disorder”: those having post-traumatic stress disorder (PTSD) and those without this diagnosis. As a result, no trustworthy difference between levels of DHEAS, cortisol and their proportion was found in PTSD-positive and PTSD-negative veterans. Each of these groups displayed the reliable reduction of DHEAS level as compared to the control group.ConclusionsThe results of our investigation demonstrate that the veterans differed significantly from the control group in the level of neurosteroids. This fact apparently cannot be linked to PTSD symptoms. Thus there is an urgent need for further examination of clinical and psychological components correlated with altered levels of DHEAS and cortisol in combat veterans.