Effects of lactic acid-fermented soymilk on lipid metabolism-related gene expression in rat liver

We examined the effects of lactic acid fermentation of soymilk on the lipid profile and lipid metabolism-related gene expression in rat liver. Male Sprague-Dawley rats aged 7 weeks were fed a control diet (AIN-93), soymilk diet, or fermented soymilk diet for 1 week or 5 weeks. The hepatic triglyceride and cholesterol contents in the soymilk (SM) group and the fermented soymilk (FSM) group were significantly lower than those in the control group after 5 weeks, but these changes had not become apparent until after 1 week. The fatty acid synthesis-related genes were more markedly down-regulated after 1 week than after 5 weeks, whereas the cytochrome p450 family 7 subfamily a polypeptide 1 (CYP7al) gene related to cholesterol catabolism was more markedly up-regulated after 5 weeks than after 1 week. This up-regulation was higher in the FSM group than in the SM group. It is assumed that the bioactive components produced by lactic acid fermentation induced the up-regulation of CYP7a1.     

Effects of dietary incorporation of linseed oil with soybean isoflavone on fatty acid profiles and lipid metabolism-related gene expression in breast muscle of chickens

The meat quality of chicken is an important factor affecting the consumer’s health. It was hypothesized that n-3 polyunsaturated fatty acid (n-3 PUFA) could be effectively deposited in chicken, by incorporating antioxidation of soybean isoflavone (SI), which led to improved quality of chicken meat for good health of human beings. Effects of partial or complete dietary substitution of lard (LA) with linseed oil (LO), with or without SI on growth performance, biochemical indicators, meat quality, fatty acid profiles, lipid-related health indicators and gene expression of breast muscle were examined in chickens. A total of 900 males were fed a corn–soybean meal diet supplemented with 4% LA, 2% LA + 2% LO and 4% LO and the latter two including 30 mg SI/kg (2% LA + 2% LO + SI and 4% LO + SI) from 29 to 66 days of age; each of the five dietary treatments included six replicates of 30 birds. Compared with the 4% LA diet, dietary 4% LO significantly increased the feed efficiency and had no negative effect on objective indices related to meat quality; LO significantly decreased plasma triglycerides and total cholesterol (TCH); abdominal fat percentage was significantly decreased in birds fed the 4% LO and 4% LO + SI diets. Chickens with LO diets resulted in higher contents of α-linolenic acid (C18:3n-3), EPA (C20:5n-3) and total n-3 PUFA, together with a lower content of palmitic acid (C16:0), lignoceric acid (C24:0), saturated fatty acids and n-6:n-3 ratio in breast muscle compared to 4% LA diet (P < 0.05); they also significantly decreased atherogenic index, thrombogenic index and increased the hypocholesterolemic to hypercholesterolemic ratio. Adding SI to the LO diets enhanced the contents of EPA and DHA (C22:6n-3), plasma total superoxide dismutase, reduced glutathione (GSH)/oxidized glutathione and muscle GSH content, while decreased plasma total triglyceride and TCH and malondialdehyde content in plasma and breast muscle compared to its absence (P < 0.05). Expression in breast muscle of fatty acid desaturase 1 (FADS1), FADS2, elongase 2 (ELOVL2) and ELOVL5 genes were significantly higher with the LO diets including SI than with the 4% LA diet. Significant interactions existed between LO level and inclusion of SI on EPA and TCH contents. These findings indicate that diet supplemented with LO combined with SI is an effective alternative when optimizing the nutritional value of chicken meat for human consumers.     

The expression of serum steroid sex hormones and steroidogenic enzymes following intraperitoneal administration of dehydroepiandrosterone (DHEA) in male rats

The adrenals of humans and primates could secrete large amounts of dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA-S) in the circulation, which act as precursors of active steroid hormones in a long series of peripheral target intracrine tissues. The marked decline of serum DHEA and DHEA-S concentrations with age in humans has been incriminated in the development of various pathologies. Therefore, this study aims to provide detailed information on the effects of the intraperitoneal injection of DHEA on circulating steroid hormones and their metabolites and their trade-off relationship over 24 h in male rats. In this study, 100 healthy adult male Sprague-Dawley (SD) rats were randomly divided into three groups: control, 25 mg kg⁻¹ DHEA-treated and 100 mg kg⁻¹ DHEA-treated. The animals were sacrificed at 0, 1.5, 3, 6, 12 or 24 h, and the samples were collected for subsequent analysis. Total cholesterol (TC) markedly decreased 3 h after the administration of 100 mg kg⁻¹ DHEA, but markedly increased 12 h after administration. The DHEA-S, progesterone (P), testosterone (T), oestradiol (E₂), cortisol (Cor) and aldosterone (Ald) concentrations also markedly increased after DHEA administration, with serum DHEA-S, T, E₂ and Cor levels peaking at 1.5 h. Over time, steroid hormone levels were depressed, but serum Cor and Ald levels were markedly elevated relative to the control group at 24 h. Furthermore, DHEA treatment produced a significant increase in P450scc, 17β-HSDIII, CYP17α and 3β-HSD mRNA expression at 1.5 h, but a decided decrease in P450scc and StAR mRNA expression at 12 and 24 h, and CYP17α and 17β-HSDIII expression at 12 h in the 100 mg kg⁻¹ DHEA group. In total, the results of the present study indicate that DHEA at high pharmacological doses may affect steroid through an effect on steroidogenic enzymes.     

Antioxidant activity of dioscorea and dehydroepiandrosterone (DHEA) in older humans

Dioscorea is a yam steroid extract used in commercial steroid synthesis and consumed by people. DHEA is a steroid which declines with age, but without known activity. This study was designed to determine whether dioscorea supplementation could increase serum dehydroepiandrosterone sulfate (DHEAS) in humans and modulate lipid levels in older people. The subjects were selected volunteers aged 65–82 years. The serum DHEAS level, lipid peroxidation and lipid profile were assessed. Three weeks of dioscorea supplementation had no affect on serum DHEAS level. However DHEA intake of 85 mg/day increased serum DHEA levels 100.3 %. DHEA and dioscorea significantly reduced serum lipid peroxidation, lowered serum triglycerides, phospholipid and increased HDL levels. Both DHEA and the steroid yam extract, dioscorea, have significant activities as antioxidant to modify serum lipid levels.     

In vivo activation of the constitutive androstane receptor beta (CARbeta) by treatment with dehydroepiandrosterone (DHEA) or DHEA sulfate (DHEA-S)

We investigated whether dehydroepiandrosterone (DHEA) or DHEA-sulfate (S) affected the activities of nuclear receptors, with special reference to constitutive androstane receptor beta (CARbeta). Administration of DHEA or DHEA-S enhanced the DNA binding of hepatic nuclear extracts to responsive elements for the retinoic acid receptor, the retinoic acid receptor beta 2 and the peroxisome proliferator activated receptor. The bound complexes were shown to be the CARbeta-RXR heterodimer by antibody-supershift assays. The expression of a target gene of CARbeta, Cyp2b10, was increased in liver by DHEA or DHEA-S treatment, suggesting that DHEA or DHEA-S actually activated CARbeta in vivo. It was suggested that the metabolic conversion of DHEA, DHEA-S to CARbeta ligands could occur in vivo and the metabolites could regulate the expression of CARbeta target gene expression. Our results provide new insights into the in vivo relationship between DHEA/DHEA-S and CARbeta activation.     

Pharmacokinetics of oral dehydroepiandrosterone (DHEA) in the ovariectomised cynomolgus monkey

Humans and primates are unique in having adrenals that secrete large amounts of DHEA and DHEA-S in the circulation. These steroids act as precursors of active androgens and estrogen's in a long series of peripheral target intracrine tissues. The marked decline of serum DHEA and DHEA-S concentrations with age in men and women has been incriminated in the development of various pathologies. This study provides detailed information on the effect of a single 50mg oral dose of DHEA on circulating estrogen's as well as androgens and their metabolites over 10h in adult ovariectomised (OVX) Cynomolgus monkeys. Serum DHEA, DHEA-S, testosterone (Testo) and androstenedione (4-dione) concentrations increased rapidly with a maximal value at approximately 1h after DHEA administration followed by a 60-80% decrease during the next 2-6h. An important sulfatation of DHEA occurs through first hepatic pass, thus, leading to a marked increase in serum DHEA-S. Serum androst-5-ene-3beta,17beta-diol and androsterone glucuronide (ADT-G) levels remained elevated on a plateau for 6h. Androstan-3alpha,17beta-diol-glucuronide, estradiol and estrone levels remained unchanged. The present data indicate the predominant transformation of the adrenal precursor DHEA into active androgens in peripheral tissues and support the importance of measurement of circulating glucuronide derivatives as index of peripheral or intracrine androgen formation and action.     

The effects of dexamethasone and dehydroepiandrosterone (DHEA) on cytokines and receptor expression in a human osteoblastic cell line: potential steroid-sparing role for DHEA

Osteoporosis and associated fractures are the most common and debilitating complication of glucocorticoid use. The use of alternative anti-inflammatory agents without the deleterious skeletal effects of glucocorticoids is needed. Dehydroepiandrosterone (DHEA) may have immunomodulatory as well as positive effects on bone. For our further understanding of the mechanisms of action of DHEA, as a steroid-sparing agent, we investigated and compared the effects of dexamethasone (DEX) and DHEA on the regulation of the downstream effector pathway of osteoclastogenesis; RANKL/OPG and a range of inflammatory/pro-resorbing cytokines and receptors using a human clonal osteoblastic cell line. The cells were treated with DEX, DHEA, and androstenedione (ANDI). The mRNA expression of RANKL and OPG was determined by real-time PCR after overnight incubation. The regulation of a broad spectrum of cytokines by DEX and DHEA was also investigated using a human cytokine/growth factor and receptor gene array consisting of 268 cytokine-related cDNAs. To confirm some of the gene expression changes, protein production was measured by ELISA. RANKL expression and RANKL/OPG ratio were increased by DEX. This effect was reversed by co-treatment with both DHEA or ANDI. Several pro-inflammatory/resorptive cytokines including IL-6, IL-4, IFN-gamma, macrophage inhibitory factor (MIF) were down-regulated not only by DEX but also by DHEA. In contrast to DEX, DHEA did not lead to suppression of growth factors including vascular endothelial growth factor (VEGF), fibroblast growth factor-5 (FGF-5), insulin-like growth factor-binding protein3 (IGF-BP3). Several new target genes previously documented to influence bone formation were up-regulated by DHEA such as Notch 2, insulin receptor, thrombin receptor (PAR1). The data suggest that DHEA has immunomodulatory properties without the catabolic effects on bone remodeling, observed with glucocorticoid use. DHEA may thus prove useful as a steroid-sparing agent in the management of inflammatory disorders such as SLE or rheumatoid arthritis. Further in vivo studies are indicated.     

Oxidative metabolism of dehydroepiandrosterone (DHEA) and biologically active oxygenated metabolites of DHEA and epiandrosterone (EpiA)--recent reports

Dehydroepiandrosterone (DHEA) is a multifunctional steroid with a broad range of biological effects in humans and animals. DHEA can be converted to multiple oxygenated metabolites in the brain and peripheral tissues. The mechanisms by which DHEA exerts its effects are not well understood. However, evidence that the effects of DHEA are mediated by its oxygenated metabolites has accumulated. This paper will review the panel of oxygenated DHEA metabolites (7, 16 and 17-hydroxylated derivatives) including a number of 5α-androstane derivatives, such as epiandrosterone (EpiA) metabolites. The most important aspects of the oxidative metabolism of DHEA in the liver, intestine and brain are described. Then, this article reviews the reported biological effects of oxygenated DHEA metabolites from recent findings with a specific focus on cancer, inflammatory and immune processes, osteoporosis, thermogenesis, adipogenesis, the cardiovascular system, the brain and the estrogen and androgen receptors.     

Synthesis and application of a photoaffinity analog of dehydroepiandrosterone (DHEA)

We have synthesized an analog of dehydroepiandrosterone (DHEA, 1) containing both a benzophenone (BP) and a biotin (Bt) group (DHEA–BP–Bt, 8). Compound 8 was prepared by functionalization on C-17 of 1. Biocytin was reacted with 4-benzoylbenzoic acid and the product was condensed with 1 containing a diamine–hexane linker. We detected specific protein bands of approximately 55, 80, and 150 kDa by SDS–PAGE analysis of vascular endothelial cell plasma membranes which had been photoirradiated in the presence of 8.     

The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats

Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10 mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β₁ (TGF-β₁) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β₁, as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β₁ and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood.     

Influence of oral dehydroepiandrosterone (DHEA) on urinary steroid metabolites in males and females

Oral dehydroepiandrosterone (DHEA) replacement therapy may have a multitude of potential beneficial effects and exerts its action mainly via peripheral bioconversion to androgens (and estrogens). A daily dose of 50-mg DHEA has been shown by us and others to restore low endogenous serum DHEA concentrations to normal youthful levels followed by an increase in circulating androgens and estrogens. As the hepatic first-pass effect may lead to a non physiological metabolism of DHEA after oral ingestion we studied the influence of two single DHEA doses (50 and 100 mg) on the excretion of steroid metabolites in 14 elderly males [age 58.8+/-5.1 years (mean +/- SEM)] with endogenous DHEAS levels <1500 ng/ml and in 9 healthy females (age 23.3+/-4.1 years) with transient suppression of endogenous DHEA secretion induced by dexamethasone (dex) pretreatment (4x0.5 mg/day/4 days). Urinary steroid profiles in the elderly males were compared to the steroid patterns found in 15 healthy young men (age 28.9+/-5.1 years). In the females the results were compared to their individual baseline excretion without dex pretreatment. Urinary steroid determinations were carried out by semiautomatic capillary gas-liquid chromatography. In both genders DHEA administration induced significant increases in urinary DHEA (females: baseline vs. 50 mg vs. 100 mg: 361+/-131 vs. 510+/-264 vs. 1541+/-587 microg/day; males: placebo vs. 50 mg vs. 100 mg: 434+/-154 vs. 1174+/-309 vs. 4751+/-1059 microg/day) as well as in the major DHEA metabolites androsterone (A) and etiocholanolone (Et). Fifty mg DHEA led to an excretion of DHEA and its metabolites only slightly above baseline levels found in young females and in young men, respectively, whereas 100 mg induced clearly supraphysiological values. After 50 mg DHEA the ratios of urinary DHEA metabolites (A/DHEA, Et/DHEA) were not significantly different between elderly males vs. young male volunteers and young healthy females versus their individual baseline levels. In conclusion, an oral dose of 30 to 50 mg DHEA restores a physiological urinary steroid profile in subjects with DHEA deficiency without evidence for a relevant hepatic first-pass effect on urinary metabolites.     

Effects of Japanese Torreya (Torreya nucifera) seed oil on the activities and mRNA expression of lipid metabolism-related enzymes in rats

The mechanism for the plasma and liver triacylglycerol-reducing effects of Japanese torreya (Torreya nucifera) seed oil containing sciadonic acid (all-cis-5, 11, 14-eicosatrienoic acid) is reported. Male SD rats were fed experimental diets containing 10% torreya, corn, or soybean oil for 4 weeks, and the activities and mRNA expression of the enzymes involved in lipid metabolism were measured in the liver. The activities of some hepatic enzymes involved in fatty acid synthesis were lower in the rats fed torreya oil.     

Neuroprotective effects of dehydroepiandrosterone (DHEA) in rat model of Alzheimer's disease

The current study was undertaken to elucidate a possible neuroprotective role of dehydroepiandrosterone (DHEA) against the development of Alzheimer's disease in experimental rat model. Alzheimer's disease was produced in young female ovariectomized rats by intraperitoneal administration of AlCl(3) (4.2 mg/kg body weight) daily for 12 weeks. Half of these animals also received orally DHEA (250 mg/kg body weight, three times weekly) for 18 weeks. Control groups of animals received either DHAE alone, or no DHEA, or were not ovariectomized. After such treatment the animals were analyzed for oxidative stress biomarkers such as hydrogen peroxide, nitric oxide and malondialdehyde, total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activities, antiapoptotic marker Bcl-2 and brain derived neurotrophic factor. Also brain cholinergic markers (acetylcholinesterase and acetylcholine) were determined. The results revealed significant increase in oxidative stress parameters associated with significant decrease in the antioxidant enzyme activities in Al-intoxicated ovariectomized rats. Significant depletion in brain Bcl-2 and brain-derived neurotrophic factor levels were also detected. Moreover, significant elevations in brain acetylcholinesterase activity accompanied with significant reduction in acetylcholine level were recorded. Significant amelioration in all investigated parameters was detected as a result of treatment of Al-intoxicated ovariectomized rats with DHEA. These results were confirmed by histological examination of brain sections. These results clearly indicate a neuroprotective effect of DHEA against Alzheimer's disease.     

Influence of maternal lipid profile on placental protein expression of LDLr and SR-BI

Maternal hyperlipidemia is a characteristic feature during pregnancy, it has been reported that modification of the maternal lipid profile can induce disturbance during pregnancy. In this study, we evaluated the impact of maternal lipid profile on the placental protein expression of two major receptors in cholesterol metabolism, the low density lipoprotein receptor (LDLr) and the scavenger receptor type B1 (SR-B1). We demonstrate an increase in the level of maternal total circulating cholesterol leads to a significant decrease in the level of the LDLr protein expression, while the level of the SR-BI expression remains unchanged. A similar change, for LDLr, is observed in association with the maternal pre-pregnancy body mass index and weight gain. Our data suggest that the LDLr plays a role in regulating cholesterol delivered to the baby from the placenta.     

Fecal dehydroepiandrosterone (DHEA) immunoreactivity as a noninvasive index of circulating DHEA activity in young male laboratory rats

Evidence suggests that dehydroepiandrosterone (DHEA) plays a key role in stress and coping responses. Fecal sampling permits assessment of hormone-behavior interactions reliably and effectively, but no previous study has compared circadian- or stress-dependent alterations between serum DHEA and its fecal metabolites. In the current study, young (28 d of age) male rats were assigned to either an experimental (n = 6) or control (n = 6) group. Rats in the experimental group were exposed to a forced swim test to assess their behavioral and physiologic response to an environmental stressor; blood samples were drawn before the test (baseline), immediately after the test, and at 2 later time points. Only fecal samples were collected from control animals. Fecal DHEA and corticosterone metabolites were monitored in all animals for 24 h. DHEA metabolites in control rats exhibited significant diurnal variation, showing a similar temporal pattern as that of corticosterone metabolites. In addition, fecal and serum DHEA levels were highly correlated. Significant peaks in both DHEA and corticosterone metabolite levels were detected. These data suggest that measures of fecal DHEA can provide a complementary, noninvasive method of assessing adrenal gland function in rats.     

Urine volume dependency of specific dehydroepiandrosterone (DHEA) and cortisol metabolites in healthy children

Urine volume should be considered as a confounder when using urinary free cortisol (UFF) and cortisone (UFE) to assess glucocorticoid (GC) status. We aimed to examine whether adrenal androgen (AA) metabolites may be also affected by urine volume in healthy children. To compare the flow dependence of GC and AA metabolites, specific GC metabolites were examined. In 24-h urine samples of 120 (60 boys) healthy children (4-10 yr), steroid profiles were determined by GC-MS analysis, UFF and UFE by radioimmunoassay. To assess daily AA and GC secretion rates, 7 quantitatively most important AA (∑C19) and GC (∑C21) metabolites were summed. Sum of DHEA and its 16α-hydroxylated metabolites were denoted as DHEA&M. Association of urine volume with AA (∑C19, DHEA&M, DHEA, 16α-hydroxy-DHEA, 3β,16α,17β-androstenetriol) and GC (∑C21, UFF, UFE, 6β-hydroxycortisol, 20α-dihydrocortisol) were examined in linear regression models. Among the examined AA metabolites, 16α-hydroxy-DHEA (β=0.56, p<0.0001) and DHEA (β=0.43, p=0.05) showed relatively strong association with urine volume. A trend was seen for ∑C19 (β=0.23, p=0.08), but not for DHEA&M (p>0.1). Regarding GC metabolites, urine volume showed a stronger association with cortisol's direct metabolites, i.e., cortisone, 6β-hydroxycortisol and 20α-dihydrocortisol (β=0.4-0.6, p<0.01) than with cortisol itself (β=0.28, p<0.05). ∑C21 was not associated with urine volume. In conclusion, like UFF and UFE, renal excretion of DHEA, 16α-hydroxy-DHEA, 6β-hydroxycortisol, and 20α-dihydrocortisol may also depend on urine volume. The intrarenal production of the latter three and cortisone might explain their relative strong water-flow-dependency. Total AA or GC secretion marker appears not to be relevantly confounded by urine volume.     

Feasibility of a liver transcriptomics approach to assess bovine treatment with the prohormone dehydroepiandrosterone (DHEA)

Background  

Within the European Union the use of growth promoting agents in animal production is prohibited. Illegal use of natural prohormones like dehydroepiandrosterone (DHEA) is hard to prove since prohormones are strongly metabolized in vivo. In the present study, we investigated the feasibility of a novel effect-based approach for monitoring abuse of DHEA. Changes in gene expression profiles were studied in livers of bull calves treated orally (PO) or intramuscularly (IM) with 1000 mg DHEA versus two control groups, using bovine 44K DNA microarrays. In contrast to controlled genomics studies, this work involved bovines purchased at the local market on three different occasions with ages ranging from 6 to 14 months, thereby reflecting the real life inter-animal variability due to differences in age, individual physiology, season and diet.     

Biotransformation of dehydroepiandrosterone (DHEA) with Penicillium griseopurpureum Smith and Penicillium glabrum (Wehmer) Westling

Microbial transformation of dehydroepiandrosterone (DHEA, 1) using Penicillium griseopurpureum Smith and Penicillium glabrum (Wehmer) Westling has been investigated. Neither fungi had been examined previously for steroid biotransformation. One novel metabolic product of DHEA (1) transformed with P. griseopurpureum Smith, 15α-hydroxy-17a-oxa-d-homo-androst-4-ene-3,17-dione (5), was reported for the first time. The steroid products were assigned by interpretation of their spectral data such as ¹H NMR, ¹³C NMR, IR, and HR-MS spectroscopy. P. griseopurpureum Smith was proven to be remarkably efficient in oxidation of the DHEA (1) into androst-4-en-3,17-dione (2). The strain was also observed to yield different monooxygenases to introduce hydroxyl groups at C-7α, -14α, and -15α positions of steroids. Preference for Baeyer–Villiger oxidation to lactonize D ring and oxidation of the 3β-alcohol to the 3-ketone were observed in both incubations. The strain of P. glabrum (Wehmer) Westling catalyzed the steroid 1 to generate both testololactone 3, and d-lactone product with 3β-hydroxy-5-en moiety 8. In addition, the strain promoted hydrogenation of the C-5 and C-6 positions, leading to the formation of 3β-hydroxy-17a-oxa-d-homo-5α-androstan-3,17-dione (9).The biotransformation pathways of DHEA (1) with P. glabrum (Wehmer) Westling and P. griseopurpureum Smith have been investigated, respectively. Possible metabolic pathways of DHEA (1) were proposed.     

Differential gene expression profile of glucocorticoids, testosterone, and dehydroepiandrosterone in human cells.

Glucocorticoids are the major immunomodulating hormones in the human body. Recently, increasing interest in androgens as immunomodulators has emerged. In particular, Dehydroepiandrosterone (DHEA) has been suggested as beneficial in the treatment of some autoimmune disorders. However, the action and role of testicular and adrenal androgens on human immune cells remains unclear. This is the first study to provide large-scale gene expression data on the action of different steroids (DHEA, glucocorticoids, and testosterone) on human peripheral blood mononuclear cells using the recently developed genomic-scale technology of microarrays. Novel computational tools and techniques such as Principal Component Analysis (PCA) were used for analysis, clustering and visualization. We have demonstrated that each steroid has its distinct gene expression profile, although DHEA and testosterone co-regulated most genes in a similar direction while glucocorticoids frequently regulated the same genes in an opposite direction. Our data suggest an important and a complex regulatory role for androgens on human immune cells that should be considered in androgen replacement or treatment strategies.