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PubMed2001

DHEA-S levels and depressive symptoms in a cohort of African American and Caucasian women in the late reproductive years.

BACKGROUND: The objective of this study was to elucidate the associations of dehydroepiandrosterone sulfate (DHEA-S) levels and depressive symptoms in African American and Caucasian women in the late reproductive years, a transitional age zone preceding the perimenopause, in which ovarian aging and associated endocrine changes begin. We had hypothesized that lower levels of DHEA-S would be associated with depressive symptoms and that, because DHEA-S levels decline with increasing age, older women would have an increased prevalence of depressive symptoms. METHODS: This cross-sectional study used a population-based urban sample recruited through random digit telephone dialing. The sample was 338 women between the ages of 35 and 47 years with regular menses. Half the sample was African American and half was Caucasian. RESULTS: Higher DHEA-S levels were associated with depressive symptoms in women in the younger half of this cohort. Lower DHEA-S levels were associated with depressive symptoms in the women in the older half of this cohort. The direction of the relationship of DHEA-S and depressive symptoms changes with age, being a positive relationship in younger women and an inverse relationship in the older women in this cohort. This change in the direction of the relationship appears to occur at a younger age in African American women. CONCLUSIONS: Our hypothesis of a relationship between low DHEA-S levels and elevated depressive symptoms was supported only in the older women in this cohort. Unexpectedly, younger women in this cohort demonstrated a positive association between DHEA-S levels and depressive symptoms. Changes in DHEA-S levels, depressive symptoms, and the relationship of other hormones in the hypothalamic-pituitary-adrenal axis need to be better understood in premenopausal women approaching perimenopause.

Adult↗

PubMed1997

Dehydroepiandrosterone (DHEA) treatment of depression.

Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basal plasma DHEA f1p4or DHEA-S levels were openly administered DHEA (30-90 mg/d x 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months: her depression ratings improved 48-72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients.

Aged↗

PubMed2002

[DHEA: desire and resistance].

DHEA is a prohormone that is secreted by the corticoadrenal glands on a nyctohemeral rhythm alike to that of testosterone. Its plasmatic level gets reduced with ageing in a great amount of individuals, but not in all. Moreover, DHEA is a neurosteroid synthesized by certain neurons. As shown by correlation studies, lowered levels of DHEA wre linked to a higher death rate, in part of the studied population. Besides, an improvement in well being as well as in some mental functions, after a 50 mg daily intake, was shown in preliminary studies. Many well-conducted studies followed which only partially confirmed the previous ones. Nowadays, it seems to be taken for granted that DHEA becomes estrogens and androgens and that its action on women is mainly an androgenic one. DHEA becomes active after intracellular transformation, which varies according to the enzymatic set of cells. Some effect on elderly women's libido, and improvement in erectile dysfunction in men without vascular pathology but a lowered DHEA level, has been observed. Thus, using DHEA in order to cure sexual troubles might be considered, although the possible negative effects of DHEA, especially on breast and prostate, have not been discarded yet. The conditions under which it could have a beneficial effect on mental functions remains to be discovered. Acknowledgement of those pathological situations, in which DHEA could prove useful, as well as the administration posology is, therefore, crucial.

Aged↗

PubMed1997

DHEA-S selectively impairs contextual-fear conditioning: support for the antiglucocorticoid hypothesis.

The authors had reported that glucocorticoids play a selective role in fear conditioning. The adrenal steroid dehydroepiandrosterone (DHEA) has been reported to act as a functional antiglucocorticoid. If DHEA has antiglucocorticoid properties, then its effects on fear conditioning might resemble those produced by adrenalectomy. The authors now report that chronic exposure to high levels of dehydroepiandrosterone sulfate (DHEA-S; converted in vivo to DHEA) produced the same pattern of results as adrenalectomy. Specifically, treatment with DHEA-S impaired contextual fear conditioning 24 hr after conditioning but not immediately after conditioning, and like adrenalectomy, DHEA-S had no effect on auditory-cue fear conditioning. Preexposure to the context before drug treatment eliminated the amnestic effects of DHEA-S, suggesting that, like adrenalectomy, DHEA-S exerted its effect by interfering with the construction of a contextual memory representation. Thus, DHEA appears to act as a functional antiglucocorticoid in the processes that mediate learning and memory.

Acoustic Stimulation↗

PubMed1997

Dehydroepiandrosterone-sulfate (DHEAS) reduces adipocyte hyperplasia associated with feeding rats a high-fat diet.

OBJECTIVE: To determine if chronic administration of a low level of dehydroepiandrosterone-sulfate (DHEAS) (10 micrograms/ml drinking water) attenuates adiposity in male Osborne-Mendel rats fed low-fat (11% of kcals) vs high fat (46% of kcals) diets. DESIGN: Rats were randomly assigned to one of four treatment groups for 6 wk in this 2 x 2 factorial study. The main effects tested were diet (low vs high fat) and DHEAS (- or +). SUBJECTS: Male Osborne-Mendel rats (initial body wt approximately 265 g). MEASUREMENTS: Adipocyte mass, size and number from two major fat depots (retroperitoneal, epididymal); mass of one subcutaneous adipose depot (inguinal); serum levels of triglycerides, insulin, glucose and DHEAS; brown adipose tissue (BAT) mass; body weight gain, food and water consumption, and residual carcass composition. RESULTS: DHEAS treatment had no effect on weight gain, food consumption or water intake. DHEAS-treated rats fed the high-fat diet had smaller fat pads containing fewer adipocytes and less carcass lipid than the non DHEAS-treated rats fed the high-fat diet. In contrast, DHEAS-treated rats fed the low-fat diet had similar levels of adipose tissue mass and cellularity compared to control animals fed the low-fat diet. CONCLUSION: Administration of a low dose of DHEAS (10 micrograms/ml or 0.8 mg/kg body wt/d) in the drinking water of young male Osborne-Mendel rats fed a high-fat diet for 6 wk reduced carcass lipid, fat depot mass and retroperitoneal and epididymal adipocyte number compared to their high-fat-fed cohorts. In this study, the antiobesity effects of DHEAS were specific to the level of dietary fat used.

Adipocytes↗

PubMed1997

Hepatic zonation of the induction of cytochrome P450 IVA, peroxisomal lipid beta-oxidation enzymes and peroxisome proliferation in rats treated with dehydroepiandrosterone (DHEA). Evidence of distinct zonal and sex-specific differences.

Dehydroepiandrosterone (DHEA) is an intermediate product in the synthesis of male and female sex hormones in the adrenal cortex of man. In livers of rats and mice DHEA increases the levels of cytochrome P450 IVA and peroxisomal beta-oxidation enzymes associated with peroxisome proliferation. Prolonged treatment of rats with DHEA induces liver tumors that are more frequent in females arising mainly in the periportal regions of the liver lobule (Metzger et al., Toxicol. Pathol. 23, 591-605, 1995). Because of paucity of information on hepatic zonation of peroxisomal response to DHEA and controversial reports on gender-specific differences of its effects the present study was undertaken using qualitative immunohistochemical and quantitative immunoelectron microscopical techniques in addition to Western blotting. Rats were treated for 24 weeks with 0.6% DHEA supplied with diet. Immunoblot analysis revealed marked induction of peroxisomal beta-oxidation enzymes, which by quantitative analysis was equally strong in male and female animals, whilst catalase and urate-oxidase were not increased. Cytochrome P450 IVA, in contrast, was induced significantly stronger in male than in female rats. Immunohistochemistry confirmed the induction of cytochrome P450 IVA showing a marked lobular gradient in female animals with strong induction in pericentral and almost no induction in periportal regions of the liver lobule. In male animals cytochrome P450 IVA was expressed more uniformly across the liver lobule. A similar sex specific zone-dependent response was observed for peroxisomes. DHEA induced in females a significant zonal gradient with marked peroxisome proliferation and a strong induction of peroxisomal hydratase/dehydrogenase in pericentral hepatocytes and a much smaller response in periportal regions. Livers of male animals, in contrast, showed a uniform peroxisomal proliferation to DHEA with only slight zonal differences. The striking homologies of the induction patterns of cytochrome P450 IVA and the peroxisome proliferation in both sexes support the notion of a functional relationship. In view of the almost exclusive periportal localization of DHEA-induced tumors in female rats in contrast to the pericentral localization of the peroxisomal proliferation shown by this study, it seems likely that other factors in addition to peroxisome proliferation may contribute to the hepatocarcinogenic effect of DHEA.

Acyl-CoA Oxidase↗

PubMed1998

DHEA treatment reduces fat accumulation and protects against insulin resistance in male rats.

The purpose of this study was to determine whether administration of dehydroepiandrosterone (DHEA) protects male rats against the accumulation of body fat the development of insulin resistance with advancing age. We found that supplementation of the diet with 0.3% DHEA between the ages of 5 months and approximately 25 months resulted in a significantly lower final body weight (DHEA, 593 +/- 18 g vs control, 668 +/- 12 g, p < 0.02), despite no decrease in food intake. Lean body mass was unaffected by the DHEA, and the lower body weight was due to a approximately 25% reduction in body fat. The rate of glucose disposal during a euglycemic, hyperinsulinemic clamp was 30% higher in the DHEA group than in the sedentary controls due to a greater insulin responsiveness. The DHEA administration was as effective in reducing body fat content and maintaining insulin responsiveness as exercise in the form of voluntary wheel running. The DHEA had no significant effect on muscle GLUT4 content. A preliminary experiment provided evidence suggesting that muscle insulin signaling, as reflected in binding of phosphatidylinositol 3-kinase to the insulin receptor substrate-1, was enhanced in the DHEA-treated and wheel running groups as compared to controls. These results provide evidence that DHEA, like exercise, protects against excess fat accumulation and development of insulin resistance in rats.

Adipose Tissue↗

PubMed2002

Dehydroepiandrosterone (DHEA) modulates the activity and the expression of lymphocyte subpopulations induced by cecal ligation and puncture.

Dehydroepiandrosterone (DHEA) exerts a variety of positive effects on the immunologic alterations after trauma and sepsis. We therefore measured the therapeutic efficacy of DHEA after cecal ligation and puncture (CLP) on the expression of lymphocyte subpopulations and on the delayed type hypersensitivity (DTH) reaction. Male NMRI-mice were randomly assigned to four different treatment groups. Treatment consisted of DHEA or saline (S) administration after CLP or laparotomy only. Flow cytometry was performed (CD4+, CD8+, and CD56 lymphocytes) after 96 hours. DTH-reaction, activity and mortality rate were documented. The CLP-induced reduction in activity and survival (mortality: 34/40) was significantly (p < 0.03) less sustained in CLP-DHEA (mortality: 22/40). The DTH-ratio (before vs. after secondary challenge) was significantly lowered in CLP-S (1.01 +/- 0.15) compared to CLP-DHEA (1.35 +/- 0.1) after 48 hours (p < 0.01). CLP-DHEA (22.2 +/- 7.9%) was associated with a statistically significant less sustained increase of CD56+ cells (p < 0.01) compared with CLP-S (49.0 +/- 6.9%). DHEA-treatment after CLP was associated with less reduction in the CD8+ T-lymphocyte subsets (p < 0.01 vs. all other groups). DHEA treatment after CLP was associated with fewer alterations in the changes of CD8+ and CD56, cells, and the DTH reaction compared with animals submitted to CLP without any treatment. This difference was associated with improved outcome (reactivity, mortality). These results suggest a modulation at specific immune reactions by DHEA treatment.

Adjuvants, Immunologic↗

PubMed2003

Dehydroepiandrosterone (DHEA) and the aging brain: flipping a coin in the "fountain of youth".

The physiological role of dehydroepiandrosterone (DHEA) and its sulphated ester DHEA(S) has been studied for nearly 2 decades and still eludes final clarification. The major interest in DHEA derives from its unique pattern of activity. Its levels exhibit a dramatic age-related decline that supports significant involvement of DHEA(S) in the aging process. Particularly relevant to the aging process is the functional decline that involves memory and cognitive abilities. DHEA is derived mainly from synthesis in the adrenal glands and gonads. It can also be detected in the brain where it is derived from a synthesis that is independent from peripheral steroid sources. For this reason DHEA and other steroid molecules have been named "neurosteroids." Pharmacological studies on animals provided evidence that neurosteroids could be involved in learning and memory processes because they can display memory-enhancing properties in aged rodents. However, human studies have reported contradictory results that so far do not directly support the use of DHEA in aging-related conditions. As such, it is important to remember that plasma levels of DHEA(S) may not reflect levels in the central nervous system (CNS), due to intrinsic ability of the brain to produce neurosteroids. Thus, the importance of neurosteroids in the memory process and in age-related cognitive impairment should not be dismissed. Furthermore, the fact that the compound is sold in most countries as a health food supplement is hampering the rigorous scientific evaluation of its potential. We will describe the effect of neurosteroids, in particular DHEA, on neurochemical mechanism involved in memory and learning. We will focus on a novel effect on a signal transduction mechanism involving a classical "cognitive kinase" such as protein kinase C. The final objective is to provide additional tools to understand the physiological role and therapeutic potentials of neurosteroids in normal and/or pathological aging, such as Alzheimer's disease.

Administration, Oral↗

PubMed1999

Lifelong treatment with oral DHEA sulfate does not preserve immune function, prevent disease, or improve survival in genetically heterogeneous mice.

OBJECTIVES: To determine whether lifelong exposure to dehydroepiandrosterone sulfate extends the lifespan or retards immune senescence in mice. DESIGN: Double-blind, placebo-controlled intervention trial. SETTING: A specific pathogen-free rodent vivarium. PARTICIPANTS: 120 mice bred as a cross between CB6F1 females and C3D2F1 males. INTERVENTION: DHEAS at 100 microg/mL in drinking water from weaning until death. MEASUREMENT: Age at death, cause of death, antibody production after erythrocyte immunization, and T cell subset profiles in peripheral blood at ages 8 and 18 months. RESULTS: DHEAS ingestion did not lead to a significant increase in mean or maximal longevity: the 95% confidence interval for DHEAS effect on mean lifespan ranged from +35 days to -80 days. There were no significant effects of DHEAS on incidence of lethal illnesses, except for a trend toward higher levels of mammary adenocarcinoma in DHEAS-treated females and mouse urinary syndrome in DHEAS-treated males. DHEAS treatment did not improve the ability of middle-aged mice to produce antibody to a foreign particulate antigen, and it did not alter the proportions of age-sensitive T cell subsets in middle-aged animals. CONCLUSION: Although differences among species in pharmacokinetics complicate interpretation of studies in which DHEA or DHEAS is administered to rodents, our data provide no support for the idea that chronic exposure to this steroid retards immune senescence or prevents late life illness.

Adenocarcinoma↗

PubMed2006

Clinical correlates of DHEA associated with post-traumatic stress disorder.

OBJECTIVE: Increased plasma dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) have been demonstrated in post-traumatic stress disorder (PTSD), but the documented beneficial effects of these steroids in enhancing mood and cognition, as well as neuroprotection, suggest their presence in PTSD may be associated with defensive rather than maladaptive effects. METHOD: We, therefore, examined plasma DHEA, DHEAS, cortisol, and the DHEA/cortisol ratio in 40 male veterans with or without PTSD, and determined their relationships to PTSD symptom severity and symptom improvement. RESULTS: The PTSD group showed significantly higher plasma DHEA and non-significantly higher DHEAS levels as well as a significantly lower cortisol/DHEA ratio, controlling for age. Regression analyses demonstrated that DHEA and DHEAS levels could be predicted by symptom improvement and coping, whereas the cortisol/DHEA ratio was predicted by severity of childhood trauma and current symptom severity. CONCLUSION: That greater symptom improvement was related to DHEA levels may suggest for a role for these hormones in modulating recovery from PTSD.

Adaptation, Psychological↗

PubMed2004

Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells.

Serum levels of the adrenal androgen dehydroepiandrosterone (DHEA) peak in men and women in the third decade of life and decrease progressively with age. Increasing numbers of middle-aged and older individuals consume over-the-counter preparations of DHEA, hoping it will retard aging by increasing muscle and bone mass and strength, decreasing fat, and improving immunologic and neurobehavioral functions. Because DHEA can serve as a precursor to more potent androgens and estrogens, like testosterone (T), dihydrotestosterone (DHT), and 17beta-estradiol (E2), supplemental DHEA use may pose a cancer risk in patients with nascent or occult prostate cancer. The steroid-responsive human LNCaP prostate cancer cells, containing a functional but mutated androgen receptor (AR), were used to compare effects of DHEA with those of T, DHT, and E2 on cell proliferation and protein and/or gene expression of AR, prostate-specific antigen (PSA), IGF-I, IGF-I receptor (IGF-IR), IGF-II, IGF-binding proteins-2, -3, and -5, (IGFBPs-2, -3, and -5), and estrogen receptor-beta (ERbeta). Cell proliferation assays revealed significant stimulation by all four steroids. DHEA- and E2-induced responses were similar but delayed and reduced compared with that of T and DHT. All four hormones increased gene and/or protein expression of PSA, IGF-IR, IGF-I, and IGFBP-2 and decreased that of AR, ERbeta, IGF-II, and IGFBP-3. There were no significant effects of hormone treatment on IGFBP-5 mRNA. DHEA and E2 responses were similar, and distinct from those of DHT and T, in time- and dose-dependent studies. Further studies of the mechanisms of DHEA effects on prostate cancer epithelial cells of varying AR status, as well as on prostate stromal cells, will be required to discern the implications of DHEA supplementation on prostatic health.

Blotting, Western↗

PubMed2006

DHEA reduces NGF-mediated cell survival in serum-deprived PC12 cells.

Adrenocortical androgens, including dehydroepiandrosterone (DHEA), are produced in the inner zone of the adrenal cortex that is in direct contact with the neural crest-derived catecholamine-producing chromaffin cells. DHEA has recently been identified as a crucial regulator of neuronal stem cell proliferation. Thus, DHEA might play a hitherto unknown role in intra-adrenal tissue formation. In the present study, we examined the influence of DHEA on nerve growth factor (NGF)-mediated survival in serum-deprived PC12 cells and analyzed the influence of DHEA on NGF-induced ERK1/2 mitogen-activated protein (MAP) kinase activation by enzyme-linked immunosorbent assay (ELISA). Cell survival promoted by NGF in serum-deprived PC12 cells and neurite outgrowth was reduced by DHEA, pointing toward a role of DHEA in the differentiation process of chromaffin cells. Furthermore, NGF-induced ERK 1/2 activation was significantly inhibited by DHEA. Hence, we speculate that DHEA might influence NGF-mediated chromaffin differentiation processes using the ERK1/2 MAP kinase pathway during adrenal tissue development.

Animals↗

PubMed2005

Dehydroepiandrosterone (DHEA) modulates GHRH, somatostatin and angiotensin II action at the pituitary level.

In view of the present controversy related to the potential beneficial effects of clinical dehydroepiandrosterone (DHEA) treatments, and considering our own previous results that reveal an influence of this steroid in pituitary hyperplasia development in vivo in rats, we decided to evaluate the role of DHEA in prolactin and GH secretion, as well as in second messengers involved, in cultured rat anterior pituitary cells. DHEA (1 x 10(-5) to 1 x 10(-7) M) did not modify basal GH or prolactin release, and a prolactin inhibitory effect was observed only for androstenediol, a metabolite of DHEA. DHEA partially prevented dopamine (1 x 10(-6) M)-induced prolactin inhibition and facilitated the prolactin-releasing effect of 10(-8) M Ang II, without modifying the resulting Ca2+(i) mobilization. Furthermore, DHEA potentiated the GH release and cAMP production induced by 1 x 10(-8) M GHRH. Finally, DHEA partially reversed the inhibitory effect of 1 x 10(-8) M somatostatin on GH, but not prolactin, release. We conclude that DHEA in vitro, directly or indirectly through conversion into metabolites, is able to modulate the hormonal response of the pituitary to hypothalamic regulators. It can enhance pituitary prolactin release and induce GH secretion. These effects could help explain some of the side effects observed in prolonged DHEA treatments in vivo and should be taken into account when considering its use in human clinical trials.

Angiotensin II↗

PubMed2000

Replacement therapy with DHEA plus corticosteroids in patients with chronic inflammatory diseases--substitutes of adrenal and sex hormones.

A dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis was found in animal models of chronic inflammatory diseases, and the defect was located in more central portions of the HPA axis. This defect of neuroendocrine regulatory mechanisms contributes to the onset of the model disease. Since these first observations in animal models were made, evidence has accumulated that the possible defect in the HPA axis in humans is more distal to the hypothalamus or pituitary gland: In chronic inflammatory diseases, such as rheumatoid arthritis, an alteration of the HPA stress response results in inappropriately low cortisol secretion in relation to adrenocorticotropic hormone (ACTH) secretion. Furthermore, it has recently been shown that the serum levels of another adrenal hormone, dehydroepiandrosterone (DHEA), were significantly lower after ACTH stimulation in patients with rheumatoid arthritis without prior corticosteroids than in healthy controls. These studies clearly indicate that chronic inflammation alters, particularly, the adrenal response. However, at this point, the reason for the specific alteration of adrenal function in relation to pituitary function remains to be determined. Since one of the down-regulated adrenal hormones, DHEA, is an inhibitor of cytokines due to an inhibition of nuclear factor-kappa B (NF-kappa B) activation, low levels of this hormone may be deleterious in chronic inflammatory diseases. We have recently demonstrated that DHEA is a potent inhibitor of IL-6, which confirmed an earlier study in mice. Since IL-6 is an important factor for B lymphocyte differentiation, the missing down-regulation of this cytokine, and others such as TNF, may be a significant risk factor in rheumatic diseases. Since in these patients, administration of prednisolone or the chronic inflammatory process itself alters adrenal function, endogenous adrenal hormones in relation to proinflammatory cytokines change. Furthermore, these mechanisms may also lead to shifts in steroidogenesis which have been demonstrated in chronic inflammatory diseases. It was repeatedly demonstrated that the serum level of the sulphated form of DHEA (DHEAS) was significantly lower in patients with chronic inflammatory diseases. Since DHEAS is the pool for peripheral sex steroids, such as testosterone and 17 beta-estradiol, lack of this hormone leads to a significant sex hormone deficiency in the periphery. This overview will demonstrate mechanisms why DHEAS is reduced in chronic inflammatory diseases. The importance of DHEAS deficiency will be demonstrated with respect to osteoporosis. As a consequence, we suggest a combined therapy with corticosteroids plus DHEA in chronic inflammatory diseases.

Adrenal Cortex Hormones↗

PubMed2001

[DHEA: orthodox or alternative medicine?].

The exact physiological role of DHEA remains unknown but DHEA supplementation has recently been proven beneficial in typical deficient states like adrenal insufficiency or major depressive illlnesses. The putative favorable effects of DHEA in other conditions remain controversial. However, recent studies confirmed positive effects of DHEA administration in healthy elderly people, mostly more than 70 years old women, on skin, bone density, muscle strength and several neuropsychological symptoms. Positive effects on sexual interest and satisfaction and sense of well-being are more consistent in elderly women than in men. The recommended administered dose is 25 mg to 50 mg once a day in women and 100 mg in men. Androgenic side effects (greasy skin, acne, increased growth of body hair) are frequent but reversible side effects. Dose adaptation is recommended in these conditions. It is justifiable to prescribe DHEA in patients with adrenal insufficiency. Other possible indications are depression and prolonged glucocorticoid therapy. In elderly people, DHEA administration might be considered in DHEA depleted-patients with skin dryness or atrophy, muscle weakness, low bone density or neuropsychological symptoms. The treatment should be taken under close medical supervision in order to detect a possible hormone-dependent cancer such as breast cancer in women and prostatic cancer in men. The patients should be informed on the potential risks of DHEA administration and on the lack of definitive proven beneficial effects of DHEA, waiting the results of well-conducted controlled double blind prospective studies.

Adjuvants, Immunologic↗

PubMed2003

[DHEA and aging].

DHEA and its ester sulfate metabolite, DHEAS, are steroids mainly secreted by the adrenal cortex, but also within the brain where they are considered as neurosteroids. No receptor was identified for DHEA or DHEAS. Their putative effects are mediated by their conversion into active sexual streroids, estradiol and testosterone, but their role is not clarified. Decreased serum levels of DHEA\DHEAS are associated with aging and have also been found in age-associated diseases. However, the results of epidemiological studies are contradictory and few therapeutic trials were published. A positive effect was found on the libido, bone status and skin in women over 70 years of age. No clear effect was evidenced on the cognitive status. Some studies showed a beneficial effect on thymic disorders, but this effect remains to be confirmed. We don't know the possible negative consequences of long-term administration of DHEA\DHEAS on cardiovascular disease and hormone-dependent cancers. Therefore, DHEA administration should not be recommended for aged people.

Adjuvants, Immunologic↗

PubMedDate not supplied

Comparative effects of DHEA and DHT on gene expression in human LNCaP prostate cancer cells.

BACKGROUND: DHEA is widely used as a dietary supplement in older men. Because DHEA can be converted to androgens or estrogens, such use may promote prostate cancer. In this study, the effects of DHEA were compared with those of DHT using gene expression array profiles in human LNCaP prostate cancer cells. MATERIALS AND METHODS: LNCaP cells were exposed to DHEA (300 nM), DHT (300 nM), or vehicle for 48 h, and mRNA expression was measured using Affymetrix HU-95 gene chips. Gene expression values were sorted in ascending order on the p-values corresponding to the extent of differential RNA expression between control and either hormone treatment. RESULTS: S100 calcium binding protein, neurotensin, 24-dehydrocholesterol reductase, and anterior-gradient 2 homologue were the four most differentially expressed genes (p-values all < 3 x 10(-5)). Nested tests of differential expression revealed lesser effects of DHEA versus DHT treatment (p < 0.01) for the S100 calcium binding protein and neurotensin genes. Microarray findings were confirmed by QRT-PCR. The top 83 genes exhibiting differential expression after DHEA or DHT were used for pathway analysis. DHT decreased expression of more genes involved in intercellular communication, signal transduction, nucleic acid binding and transport, and in structural components, such as myosin and golgin, than DHEA. CONCLUSION: These data revealed consistent, measurable changes in gene expression patterns following treatment of LNCaP prostate cancer cells with DHEA and DHT. Understanding the mechanisms of DHEA versus DHT actions in the prostate may help clarify the separate and interactive effects of androgenic and estrogenic actions in prostate cancer progression.

Adjuvants, Immunologic↗