SEARCH · PubMed Health

Results for “DHEAS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources

PubMed1991

Differential effects of dehydroepiandrosterone (DHEA) on murine lymphopoiesis and myelopoiesis.

Dehydroepiandrosterone (DHEA) inhibits murine lymphopoiesis, especially after sublethal irradiation, without affecting mature lymphocyte function. We demonstrate here that dietary DHEA differentially affected myelopoiesis and lymphopoiesis in sublethally irradiated mice. Erythropoietic progenitor cell and stem cell function was not affected by DHEA although the magnitude of granulopoiesis was slightly reduced. Regeneration of marrow B220+ B cells, natural killer (NK) function, and thymus repopulation were significantly delayed in DHEA-fed mice. Interleukin 2 (IL-2) failed to restore NK activity of DHEA-fed mice to normal levels. Marrow from DHEA-fed mice contained competent thymocyte progenitors capable of repopulating thymi of irradiated hosts fed a control diet but not those fed the DHEA diet. Thus DHEA inhibits lymphopoiesis while sparing myelopoiesis, affecting the growth and maturation of T, B, and NK cells by a mechanism other than the inhibition of IL-2 production.

Animals↗

PubMed1996

Studies of dehydroepiandrosterone (DHEA) as a therapeutic agent in systemic lupus erythematosus.

Several lines of investigation led to the consideration of dehydroepiandrosterone (DHEA) as a candidate for hormonal therapy in systemic lupus erythematosus, including DHEA deficiency in patients with SLE, the effects of sex steroids on SLE, the immunomodulatory effects of DHEA, and the results of DHEA in animal models of SLE. Uncontrolled observations in 50 patients suggested that DHEA has overall benefits for lupus activity, alleviating specific lupus symptoms as well the systemic manifestations of lupus, with incremental benefits over 3 to 12 months of treatment. DHEA, which was very well tolerated and safe, appeared to decrease the number of lupus flares and to have a steroid sparing effect. These results were confirmed in a small placebo-controlled trial, although the results were of borderline statistical significance. Currently, a number of additional trials with DHEA are underway, and it is anticipated that DHEA will find its place as a useful agent in the treatment of SLE.

Dehydroepiandrosterone↗

PubMedDate not supplied

DHEA attenuates catecholamine secretion from bovine adrenal chromaffin cells.

Dehydroepiandrosterone (DHEA) is a putative anti-stress agent and stress is associated with the secretion of catecholamine from the adrenal gland, but the effects of DHEA on catecholamine secretion are not fully understood. Using bovine chromaffin cells, we found that DHEA inhibited catecholamine secretion and cytosolic Ca(2+) ([Ca(2+)](i)) rise coupled with nicotinic acetylcholine receptor (nAChR) without exerting an effect on (3)H-nicotine binding. In the case of high K(+) stimulation, DHEA effectively suppressed secretion without affecting [Ca(2+)](i) rise. Trifluoperazine (TFP), a calmodulin inhibitor, was capable of counteracting the inhibition of DHEA on high K(+)-induced secretions. In permeabilized cells, DHEA suppressed the Ca(2+)-induced secretion. These results suggest that DHEA (a) acts as a channel blocker that suppresses Ca(2+) influx and subsequent secretions associated with nAChR, or (b) affects the intracellular secretion machinery to suppress high K(+)-induced secretions without affecting the high K(+)-induced [Ca(2+)](i) rise.

Adrenal Medulla↗

PubMed1999

Modulation of chemical carcinogen-induced unscheduled DNA synthesis by dehydroepiandrosterone (DHEA) in the primary rat hepatocytes.

Modulation of unscheduled DNA synthesis by dehydroepiandrosterone (DHEA) after exposure to various chemical carcinogens was investigated in the primary rat hepatocytes. Unscheduled DNA synthesis was induced by treatment of such direct acting carcinogens as methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) or procarcinogens including benzo(a)pyrene (BaP) and 7,12-dimethylbenz(a)anthracene (DMBA). Unscheduled DNA synthesis was determined by measuring [methyl-3H]thymidine radioactivity incorporated into nuclear DNA of hepatocytes treated with carcinogens in the presence or absence of DHEA. Hydroxyurea (5x10(-3) M) was added to growth medium to selectively suppress normal replication. DHEA at concentrations ranging from 1x10(-6) M to 5x10(-4) M did not significantly inhibit unscheduled DNA synthesis induced by either MMS (1x10(-4) M) or EMS (1x10(-2) M). In contrast, DHEA significantly inhibited unscheduled DNA synthesis induced by BaP (6.5x10(-5) M) and DMBA (2x10(-5) M). DHEA-induced hepatotoxicity in rats was examined using lactate dehydrogenase (LDH) release as an indicator of cytotoxicity. DHEA exhibit no significant increase in LDH release compared with the solvent control at 18 h. These data suggest that nontoxic concentration of DHEA does not affect the DNA excision repair process, but it probably influence the enzymatic system responsible for the metabolic activation of procarcinogens and thereby decreases the amount of the effective DNA adducts formed by the ultimate reactive carcinogenic species.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

Serum DHEAS levels correlate with platelet cGMP in normal women.

Several studies suggest that DHEAS is a protective factor against atherosclerosis and coronary artery disease in man, but the mechanism of its biological role is unclear. Recently, it has been suggested that DHEAS can retard atherosclerosis formation through an increase in nitric oxide (NO) production by increasing E2 synthesis. The aim of the study was to evaluate the platelet cGMP concentrations (i.e. a marker of NO production) and the serum levels of DHEAS and E2 in normal females. Blood samples were taken from 51 normal women (age 42.3+/-1.9 yr, range: 22-67 yr, BMI 23.0+/-0.6 kg/m2) to evaluate platelet cGMP concentrations and serum levels of DHEAS and E2. To determine the platelet cGMP content, platelet rich plasma (PRP) was incubated at 37 C (30 min) in the presence of IBMX. The amount of platelet cGMP was measured by a cGMP (3H) assay kit. In all subjects the mean of platelet cGMP was 536.2+/-45.3 fmol/10(6) platelets and the mean of serum DHEAS and E2 was 151.4+/-13.9 microg/dl and 34.7+/-6.1 pg/ml, respectively. In all subjects DHEAS positively correlates with cGMP (p<0.001, r=0.513) and with E2 (p<0.001, r=0.650); furthermore E2 positively correlates with cGMP (p<0.001, r=0.663). In conclusion our data support the hypothesis that DHEAS exerts its antiatherogenic effect by increasing the NO production directly and/or by increasing the E2 synthesis.

Adult↗

PubMed2006

Evaluation of CD detection in an HPLC system for analysis of DHEA and related steroids.

The biological importance of dehydroepiandrosterone (DHEA) is reflected by the fact that DHEA is a crucial precursor of the biosynthesis of the steroidal sex hormones. Simultaneous separation of DHEA, dehydroepiandrosterone sulfate (DHEA-S), pregnenolone, androstenedione and testosterone has been accomplished by reversed-phase ion-pair high-performance liquid chromatography (RP-IP-HPLC) based on isocratic elution applying circular dichroism (CD) detection at 295 nm. Addition of tetrabutylammonium hydrogensulfate to the mobile phase increases the retention of DHEA-S on the C8-silica column by an apparent ion-pairing mechanism without affecting the retention of the other (non-ionic) steroids. CD spectroscopy provides highly selective detection of compounds possessing optically active absorption bands and the separation is even more selective in the higher wavelength range applied. The linearity of the steroid concentration (c, mg mL(-1)) versus peak area was tested in the concentration range of 0.5-2 mg mL(-1) (injected quantities were 10-40 microg). The relative standard deviation (RSD) values for DHEA and DHEA-S indicated a good intra-assay and inter-assay precision of the method.

Chromatography↗

PubMed1996

The neurosteroid dehydroepiandrosterone sulfate (DHEAS) enhances hippocampal primed burst, but not long-term, potentiation.

Dehydroepiandrosterone sulfate (DHEAS), which is synthesized in the brain and in the periphery, is known to affect the excitability of hippocampal neurons. However, its influence on electrophysiological plasticity has not been addressed. We have studied the effects of DHEAS on primed burst (PB) and long-term (LTP) potentiation, two electrophysiological models of memory. PB potentiation is a lasting increase in the amplitude of the CA1 population spike produced by minimal (threshold) electrical stimulation; LTP is produced by more extensive (supra-threshold) stimulation. Whereas intermediate doses (24 and 48 mg/kg, s.c.) of DHEAS given to rats enhanced PB potentiation, low (6 mg/kg) and high (96 mg/kg) doses were ineffective. LTP was not affected by any dose of DHEAS. The inverted-U relationship between DHEAS and PB potentiation is consistent with previous work demonstrating an inverted-U dose-dependent enhancement of memory by DHEAS. The present findings suggest that DHEAS could enhance memory by facilitating the induction of neural plasticity.

Animals↗

PubMed2004

DHEAS as a new diagnostic tool.

Dehydroepiandrosterone sulfate (DHEAS) is a 19-carbon steroid, situated along the steroid metabolic pathway. It is the most abundant circulating steroid hormone in the body and can be converted to either androgens or estrogens. Their physiological and pathological functions have not yet been fully identified. Serum DHEAS concentrations peak at around age 25 years and then decline steadily over the following decades. Due to its long half-life and high concentration in the blood, the levels of DHEAS remain the same 24 h a day. This makes DHEAS a very interesting new diagnostic tool for both scientific research and clinical diagnostics. Moreover, circulating concentrations of DHEAS can be changed by many factors, such as endogenous production, hormone supplementation, many kinds of drugs, and many types of disease states. As research moves forward to better understand the relationships of DHEAS with health and disease, it is essential that studies should be designed to control for the influence of many factors on serum DHEAS concentrations.

Animals↗

PubMed2005

Lowered DHEA-S plasma levels in adult individuals with autistic disorder.

The aim of this study was to determine for the first time neurosteroid levels, dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) in particular, in a group of adult patients with autistic disorder and compare these levels with normal healthy individuals. Levels of DHEA, DHEA-S and cortisol were compared between 15 adult drug-free patients with autistic disorder and 13 healthy controls. The Ritvo-Freeman Real-Life Rating Scale (RLRS) and the Overt Aggression Scale (OAS) were assessed as a measure of symptom severity. Significant lower DHEA-S levels were observed in the group with autistic disorder as compared to controls (p < 0.05). DHEA-S levels appear to be low in patients with autistic disorder and, while speculative, may play a role in the etiopathophysiology of the disorder.

Adult↗

PubMed2006

State and trait related predictors of serum cortisol to DHEA(S) molar ratios and hormone concentrations in schizophrenia patients.

OBJECTIVE: In previous studies we have demonstrated high serum molar ratios of cortisol to dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) [together abbreviated DHEA(S)], and the value of both cortisol/DHEA(S) molar ratios for prediction of responsivity to antipsychotic treatment in schizophrenia patients. The present study aimed to examine the contribution of anxiety, and severity of symptoms to the prediction of serum cortisol, DHEA(S) levels and two molar ratios across three examinations. METHOD: Serum concentrations of cortisol and DHEA(S)were examined in 43 schizophrenia inpatients and in 20 age matched healthy controls at baseline, and after 2 and 4 weeks. The Positive and Negative Symptom Scale and the State-Trait Anxiety Inventory scores were used as independent variables for multiple regression analysis. RESULTS: Despite clinical improvement during the study period cortisol/DHEA(S) molar ratios were found persistently elevated as compared to healthy controls. Multiple regression analysis revealed that across three examinations cortisol/DHEA(S) molar ratios negatively associated with trait-anxiety (partial R(2)=7-14%) rather than with negative symptoms (partial R(2)=3-6%). Age and age of onset account for 12.7% for variability of cortisol/DHEAS ratio. Serum cortisol concentrations are predicted by trait and state-anxiety, activation symptoms and daily doses of antipsychotics. A small portion of variability in serum DHEA levels (R(2)=9%) is associated with symptom severity, while DHEAS levels were predicted by age at examination and age of onset. CONCLUSION: Elevated serum cortisol/DHEA(S) molar ratios were attributed to trait-anxiety and age rather than to clinical symptoms. The findings may indicate persistent dysfunction of the hypothalamic-pituitary-adrenal axis that is independent of the patients' clinical state.

Adult↗

PubMed2005

Blood DHEAS concentrations correlate with cognitive function in chronic schizophrenia patients: a pilot study.

There is evidence that neurosteroids such as DHEA and its sulfated form DHEAS can modulate cognitive function. We hypothesize that DHEA/S concentrations may be linked to cognitive impairment in schizophrenia. The aim of this pilot study was to test this hypothesis by examining the relationship between blood levels of DHEAS and cognitive function. The performance of 26 stable medicated chronic schizophrenia patients in a range of neuropsychological domains including verbal memory (Wechsler Memory Scale), executive function (AIM), memory of faces (PFMT), memory for objects (VOLT) and identification of facial emotional expressions (PEAT) was assessed. Single morning blood samples were assayed for levels of DHEAS and cortisol. Significant associations were found between DHEAS levels and DHEAS/Cortisol ratio and verbal memory, executive function and memory for faces. The relationship was independent of the age related reduction in DHEAS levels. These preliminary results suggest that DHEAS may be associated with cognitive impairment in schizophrenia.

Adult↗

PubMed2006

Dehydroepiandrosterone (DHEA) is an anabolic steroid like dihydrotestosterone (DHT), the most potent natural androgen, and tetrahydrogestrinone (THG).

We have recently taken advantage of the unique power of DNA microarrays to compare the genomic expression profile of tetrahydrogestrinone (THG) with that of dihydrotestosterone (DHT), the most potent natural androgen, thus clearly demonstrating that THG is an anabolic steroid. In 2004, the U.S. Controlled Substances Act has been modified to include androstenedione (4-dione) as an anabolic steroid. However, despite the common knowledge that dehydroepiandrosterone (DHEA) is the precursor of testosterone, DHEA has been excluded from the list of anabolic steroids. We thus used the same DNA microarray technology to analyze the expression profile of practically all the 30,000 genes of the mouse genome modulated by DHEA and DHT in classical androgen-sensitive tissues. Daily subcutaneous injections of DHT (0.1mg) or DHEA (3mg) for 1 month in gonadectomized C57BL6/129 SV mice increased ventral prostate, dorsal prostate, seminal vesicle and preputial gland weight (p<0.01 for all tissues). As early as 24h after single injection of the two steroids, 878, 2681 and 14 probe sets were commonly stimulated or inhibited (p<0.01, change> or =30%), in the prostate (ventral+dorsal), seminal vesicles and preputial glands, respectively, compared to tissues from gonadectomized control animals. After 7 days of daily treatment with DHEA and DHT, 629, 919 and 562 probe sets were commonly modulated in the same tissues while after 27 days of treatment, 1195, 5127 and 2883 probe sets were modulated, respectively. In analogy with the data obtained with THG, the present microarray data provide an extremely precise and unquestionable genomic signature and proof of the androgenic/anabolic activity of DHEA. Such data add to the literature showing that DHEA is transformed into androgens in the human peripheral tissues as well as in laboratory animal species, including the monkey, thus exerting potent androgenic/anabolic activity. The present microarray approach to identify anabolic compounds is applicable to all potential androgenic/anabolic compounds.

Anabolic Agents↗

PubMed2005

Different effect of hormone replacement therapy, DHEAS and tibolone on endothelial function in postmenopausal women with increased cardiovascular risk.

Menopause is associated with an increased cardiovascular risk and with a decrease in endothelial function. Hormone replacement therapy (HRT) improves endothelial function in post-menopausal women (PMW) without established atherosclerosis. New alternative treatments, among which tibolone (T) and DHEAS have been suggested to reduce postmenopausal cardiovascular risk. Although, in vitro animal studies have suggested that T and DHEAS improve endothelial function, their effect in humans has never been tested. The aim of the present study was to compare the effects of HRT (continuous combined 0.625 mg conjugated equine estrogen plus 2.5 mg/d medoxyprogesterone) DHEAS and T on endothelium-dependent flow-mediated vasodilatation (FMD), plasma nitrite, nitrate and endothelin-1 levels in 16 PMW with increased cardiovascular risk in a double-blinded, double-crossover study. Women were randomized and treated for 4 weeks with HRT, T or DHEAS. Brachial artery diameter, FMD, endothelin-1 and plasma nitrite and nitrate levels were measured at baseline and after each treatment phase. Brachial artery diameters remained unchanged after each treatment phase. HRT significantly improved FMD compared to both baseline and to T and DHEAS therapies while no effect of T or DHEAS on FMD was noted. In conclusion, HRT, but neither T nor DHEAS, improves endothelial function and reduces plasma levels of endothelin-1 in PMW at risk of CAD.

Brachial Artery↗

PubMed2001

Aggressive behavior induced by the steroid sulfatase inhibitor COUMATE and by DHEAS in CBA/H mice.

The steroid sulfatase enzyme (STS) regulates the formation of dehydroepiandrosterone (DHEA) from dehydroepiandrosterone-sulfate (DHEAS). DHEAS is a well-known negative allosteric modulator of the GABA(A) receptor-gated chloride channels. It is classified as an excitatory neurosteroid. The implication of GABA(A) receptor activity in aggressive behavior in rodents is well-documented. In addition a genetic correlation between STS level in the liver and aggressive behavior across 12 strains of mice suggest that STS activity could be involved in aggression in mice. We assessed herein whether COUMATE (an STS inhibitor) and DHEAS modulate aggression in CBA/H mice. We hypothesized that inhibiting STS activity in vivo followed by DHEAS injections which increase the level of sulfated steroid that cross the blood-brain barrier and then modulate neurotransmitter receptors could modify the attack behavior in mice. COUMATE (10 mg/kg) was administrated p.o. alone or in combination with the neurosteroid DHEAS (0-50 mg/kg) i.p. Animals were thereafter tested for aggression. A single dose of COUMATE significantly inhibited STS activity both in the brain (70.57%) and in the liver (87%) 24 h following administration. Behavioral tests showed that the inhibitor and DHEAS enhanced aggressive behavior when animals were simultaneously subjected to both molecules. These results confirm the correlation between aggressive behavior and STS concentration in mice. In addition, we confirm that the steroid metabolism can modulate the behavior in rodents.

Aggression↗

PubMed2002

Chemoprevention of precursors to colon cancer by dehydroepiandrosterone (DHEA).

Although dehydroepiandrosterone (DHEA) is recognized as one of the major adrenal androgens, its precise physiological role in the human endocrine system remains to be elucidated. In particular, the effect of DHEA on carcinogenesis has not been fully characterized. We undertook this study to determine whether DHEA has a chemopreventative effect on the precursors of colon cancer in a murine model of azoxymethane (AOM)-induced aberrant crypt foci (ACF). The number of ACF was significantly decreased in mice treated with 0.4% (p < 0.001) and 0.8% DHEA (p < 0.001), but there were no significant differences between DHEA-treated and control mice in terms of the ACF size, 3-catenin expression or level of dysplasia. This is the first study of colon cancer carcinogenesis demonstrating that DHEA treatment can decrease the number of ACF without apparently modifying their malignant potential. These data strongly suggest that DHEA might be a potential chemopreventative agent against human colon cancer.

Adjuvants, Immunologic↗

PubMed2001

Memory-enhancing effects of DHEAS in aged mice on a win-shift water escape task.

The steroid hormone, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been implicated in age-associated deficits in memory. Numerous studies have demonstrated the effectiveness of these neurosteroids to enhance retention and ameliorate the effects of various memory-blocking agents, but few studies have directly assayed their effects on memory in aged animals. The present study investigated the memory-enhancing effects of DHEAS in a win-shift (nonmatching-to-sample) task in aged mice using water escape motivation. Sixteen CD-1 mice, 18-20 months old, were trained to a moderate criterion of 7/10 correct trials and were then divided into two equal groups based on acquisition performance. One group received oral administration of DHEAS (1.5 mg/mouse/day) in a vehicle solution (0.0015% methyl salicylate) while the other group received the vehicle alone. DHEAS effects were assessed using a procedure in which delay intervals (0, 120, and 240 s) were interposed between sample and comparison trials over the course of three test sessions. The group receiving DHEAS recorded significantly higher retention scores across 3 days of testing, particularly at the 120-s delay interval, indicating that DHEAS enhanced working memory in these aged animals.

Aging↗

PubMed1998

The steroid hormone dehydroepiandrosterone (DHEA) breaks intranasally induced tolerance, when administered at time of systemic immunization.

The induction of intranasal tolerance might be dependent on specific characteristics of mucosal, nose-draining lymph nodes. Such a specific characteristic might lie in the metabolism of the steroid hormone DHEA. Conversion of the prohormone DHEAS into DHEA is dependent on DHEAS-sulphatase activity in lymph nodes. This activity is low in mucosa-draining lymph nodes compared to peripheral lymph nodes, leading to differences in microenvironment. However, administration of DHEA before the induction of intranasal tolerance, could not change tolerance induction. We next determined the effect of DHEA after the induction of intranasally induced tolerance and demonstrated that the steroid hormone and some of its derivatives are able to break tolerance, when administered at time of systemic immunization. These findings might have implications for the regulation of intranasal tolerance and the use of DHEA.

Administration, Intranasal↗

PubMed2000

DHEA treatment for HIV+ patients: effects on mood, androgenic and anabolic parameters.

The goal of this pilot study was to evaluate the effect of dehydroepiandrosterone (DHEA) on depressed mood and fatigue in HIV+ men and women, unselected for baseline DHEA level. Secondary questions concerned treatment effects on libido and body cell mass, on serum testosterone levels, and elicitation of short-term side effects. Treatment consisted of an open-label 8-week trial using DHEA doses from 200 to 500 mg/day. Mood responders were maintained for another 4 weeks, then randomized to a double blind placebo controlled 4-week discontinuation trial. Forty-five patients, including six women, entered the trial. Of 32 week 8 completers, mood was much improved in 72%, and 81% were rated responders with respect to fatigue. Response on either parameter was unrelated to baseline serum DHEA level. Twenty-one patients entered the double blind discontinuation phase. No differences in relapse rate between placebo and DHEA groups were observed for either mood or fatigue. Body cell mass increased significantly by week 8, and this improvement was maintained throughout the double blind phase for patients in both treatment conditions. Libido increased significantly as well. DHEA therapy did not have an effect on CD4 cell count or on serum testosterone levels in men. In conclusion, DHEA may be a promising treatment for HIV+ patients with depressed mood and fatigue, although persistence of response even in placebo-treated patients during the discontinuation phase leaves unresolved questions. A parallel group double blind clinical trial is indicated as the next step to more clearly identify therapeutic efficacy.

Adult↗