Failure of Dehydroepiandrosterone to Influence Energy and Protein Metabolism in Humans*

Welle, Stephen; Józefowicz, Ralph F.; Statt, Marcia

doi:10.1210/jcem-71-5-1259

Cited by 123 publications

(43 citation statements)

References 6 publications

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“…DHEA was administered to humans and mammals in high doses with only minor adverse effects, and it is devoid of the harmful immunosuppressive effects of GC (37). Its efficacy in the protection from endotoxemic shock as well as in protection from lethal viral infections warrants further investigations on its mechanisms of action, its activities on the immune system, and on the possibility of treating various infections and other pathologic states of the immune system with DHEA.…”

Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production

Danenberg

Alpert

Lustig

et al. 1992

Antimicrob Agents Chemother

120

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Recent reports have demonstrated an immunomodulating activity of dehydroepiandrosterone (DHEA) different from that described for glucocorticoids. The present study was designed to test DHEA's activity in endotoxic shock and to investigate its effect on endotoxin-induced production of tumor necrosis factor (TNF).Mortality of CD-1 mice exposed to a lethal dose of lipopolysaccharide (LPS; 800 ,ug per mouse) was reduced from 95 to 24% by treatment with a single dose of DHEA, given 5 min before LPS. LPS administration resulted in high levels of TNF, a response that was significantly blocked by DHEA, both in vivo and in vitro. DHEA treatment also reduced LPS-induced increments in serum corticosterone levels, a parameter considered not to be mediated by TNF. In another experimental model, mice sensitized with D-galactosamine, followed by administration of recombinant human TNF, were subjected to 89% mortality rate, which was reduced to 55% in DHEA-treated mice. These data show that DHEA protects mice from endotoxin lethality. The protective effect is probably mediated by reduction of TNF production as well as by effecting both TNF-induced and non-TNF-induced phenomena.Dehydroepiandrosterone (DHEA) is an abundantly secreted, weak androgenic, adrenocortical steroid hormone that is an intermediate in the biosynthesis of other hormones including testosterone and estradiol-171. Concentrations of DHEA in plasma gradually decline after the third decade of life, reaching 10 to 20% of the peak level in the e!derly (20,24).The precise biological functions of DHEA are uncertain. A growing body of evidence, both experimental and epidemiological, suggests an inverse relationship between low levels of DHEA in serum and morbidity from atherosclerotic cardiovascular disease (1, 9), cancer (10,11,26) and human immunodeficiency virus (HIV) infection (31). Moreover, low levels of DHEA were found to be independently predictive of death from any cause (1).Recent reports proposed an immunomodulating activity of DHEA. It was found to prevent dexamethasone-induced thymic involution in mice (19), increase interleukin-2 production both in vitro and in vivo (6), and prevent the development of systemic lupus erythematosus in a mouse model (18). Lymphopoiesis, but not myelopoiesis or erythropoiesis, was inhibited in irradiated mice fed with DHEA (28, 29). Although lacking an in vitro antiviral activity, DHEA was effective in protecting mice from a variety of lethal viral infections (2, 17).During the course of gram-negative infections, bacterial cell wall products, such as endotoxin (lipopolysaccharide [LPS]), are released, inducing intense pathophysiologic alterations (22). It is not LPS alone that causes the damage, but rather the host response, which may be described as an "overshoot" of the immune system. One of the major responses to LPS in vivo is the rapid production and secretion of cytokines, the soluble mediators of inflammation, like tumor necrosis factor (TNF) (3,5).LPS toxicity can be reduced by administration of potent immunosuppresi...

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Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production

Danenberg

Alpert

Lustig

et al. 1992

Antimicrob Agents Chemother

120

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“…The study by Nestler et al (6) reported a 31% decrease in underwater weighingmeasured percent body fat after only 4 weeks of DHEA treatment at 1600 mg/day (6). However, these results were not repeated in obese or normal men following similar protocols (136,140). The study by Flynn et al (132) reported a trend for a decrease in body weight, with no changes in body composition after 12 weeks of 100 mg/day oral DHEA in 39 healthy older men (132).…”

Section: Exogenous Dheamentioning

confidence: 97%

Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of human studies

Tchernof

Labrie

2004

European Journal of Endocrinology

152

100

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The age-related decline in serum dehydroepiandrosterone (DHEA) and its sulfated ester (DHEA-S) has suggested that a relative deficiency of these steroids may be causally related to the development of chronic diseases generally associated with aging, including insulin resistance, obesity, cardiovascular disease, cancer, reductions of the immune defense, depression and a general deterioration in the sensation of well-being. The numerous studies which have focused on the link between DHEA and cardiovascular disease have generally been inconsistent, generating much debate and controversy on this issue. The present article is an analysis of studies on the relationship between endogenous DHEA or DHEA-S, obesity and cardiovascular disease risk, as well as DHEA treatment studies. Elevated plasma levels of free DHEA are associated with reduced obesity in both men and women, and with smaller abdominal body fat accumulations in men. However, contradictory results have been reported regarding the relationships between the sulfate ester DHEA-S and adiposity. Age differences in the populations studied may have been a confounding factor in these associations. On the other hand, DHEA-S level is not a predictor of cardiovascular disease endpoints in women, and appears to be a relatively weak one in men. DHEA intervention studies suggest that the effects of DHEA on serum lipids are, at best, modest or non-significant. The uncertainty as to whether endogenous and exogenous DHEA should be considered cardioprotective is related to discrepancies in the literature on this topic. Several studies may have been plagued by methodological problems such as low power, unreliable analytical methods, confounding factors or other differences in the populations studied. As a consequence, the original reports demonstrating dramatic effects of either endogenous or exogenous DHEA on cardiovascular disease risk have never been replicated. We propose that the effects of DHEA on cardiovascular disease risk (either favorable or unfavorable) should be considered to be much more modest than previously believed.

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“…9 Nevertheless, the relationship of DHEAS and DHEA to lipids and lipoproteins in men is still debated; some studies show either signi®cant inverse correlation 9,10 or no correlation with lipids, particularly triglycerides. 11,12 Studies evaluating the impact of DHEA replacement on lipids and lipoproteins in men have reported either no modi®cation, 13,14 or signi®cant decrease in total and HDL cholesterol 15 or in total and LDL cholesterol. 16 Physical exercise can be effective for controlling diabetes and reducing serum lipid levels and other CHD risk factors.…”

Section: Introductionmentioning

confidence: 99%

Exercise training-induced triglyceride lowering negatively correlates with DHEA levels in men with type 2 diabetes

et al. 2001

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OBJECTIVE:To investigate the effect of an exercise training program on lipid pro®le in correlation with DHEA level and body weight and body composition in type 2 diabetic men. DESIGN: Longitudinal, controlled clinical intervention study with exercise training consisting of an 8 week supervised program of aerobic exercise (75% VO 2 peak, 45 min), twice a week and intermittent exercise, once a week, on a bicyle ergometer. SUBJECTS: Sixteen men (age 45.4 AE 7.2 y (mean AE s.d.), HbA1c 8.15 AE 1.7%, body mass index (BMI) 29.6 AE 4.6 kgam 2 ) were randomly divided into two groups: trained group (n 8) and control group (n 8 P`0.001), and DHEA levels (11.00 AE 3.10 vs 14.25 AE 4.10 nmolal, P`0.05) with no modi®cation in body weight. Changes in triglycerides were negatively correlated with changes in DHEA (r À0.81, P 0.03). This correlation was independent of changes in abdominal fat distribution. CONCLUSION: Training decreases abdominal fat depots, improves muscular mass and affects favourably triglyceride and DHEA levels. Changes in triglycerides and DHEA were inversely related.

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Failure of Dehydroepiandrosterone to Influence Energy and Protein Metabolism in Humans*

Cited by 123 publications

References 6 publications

Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production

Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production

Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of human studies

Exercise training-induced triglyceride lowering negatively correlates with DHEA levels in men with type 2 diabetes

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