Title: Replacement Therapy with Dhea Plus Corticosteroids in Patients with Chronic Inflammatory Diseases–Substitutes of Adrenal and Sex Hormones
Author: Straub, R. H.; Scholmerich, J.; Zietz, B.; 2000)
Journal: Z Rheumatol; V. 59 Suppl 2; Pages: II/108-18
Abstract: 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.
Notes: Journal Article
Review
Review, Tutorial
Author Address: Laboratory of Neuroendocrinoimmunology, Department of Internal Medicine I, University Hospital, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg, Germany.
Title: Interactions between the Hypothalamic-Pituitary-Adrenal Axis and Allergic Inflammation
Author: Schleimer, R. P.; (Date: Nov, 2000)
Journal: J Allergy Clin Immunol; V. 106; Issue: 5 Suppl; Pages: S270-4
Abstract: It is undeniable that glucocorticoids are remarkably effective in the therapeutic management of allergic diseases such as rhinitis, atopic dermatitis, and asthma. The potent synthetic drugs used clinically are analogues of the endogenous adrenal hormone cortisol. A growing body of evidence now suggests that endogenous cortisol, which is produced in significant quantities by the body in a diurnal rhythm, is an important regulator of allergic disease expression and allergic inflammatory responses: lung function varies along with plasma cortisol levels; the number of circulating inflammatory cells varies with plasma cortisol levels; and low levels of endogenous cortisol may be associated with risk for asthma. Treatment studies suggest that the administration of inhaled or oral steroids is probably more effective when given in the evening when endogenous cortisol levels are low. Conversely, challenge studies show clearly that antigen-induced late-phase responses occur less readily if the challenge is performed in the morning at a time when endogenous cortisol levels are high. Finally, inflammatory responses may induce the production of cortisol by the hypothalamic-pituitary-adrenal axis as a feedback mechanism. Paradoxically, some inflammatory cytokines may induce resistance of inflammatory cells to glucocorticoids. The available information describes a complex yet balanced interplay between adrenal cortisol production and allergic inflammation.
Notes: Journal Article
Review
Review, Tutorial
URL: http://www.mosby.com/scripts/om.dll/serve?action=searchDB&searchDBfor=art&artType=abs&id=a110162&target=
Author Address: Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224-6801, USA.
Title: Endogenous Glucocorticoids and Antigen-Induced Acute and Late Phase Pulmonary Responses
Author: Peebles, R. S., Jr.; Togias, A.; Bickel, C. A.; Diemer, F. B.; Hubbard, W. C.; Schleimer, R. P.; (Date: Sep, 2000)
Journal: Clin Exp Allergy; V. 30; Issue: 9; Pages: 1257-65
Abstract: BACKGROUND: Several studies suggest that endogenous glucocorticoids can dampen the severity of experimental allergic reactions in animals. OBJECTIVE: To investigate the influence that endogenous glucocorticoids have on the course of IgE-mediated pulmonary early and late phase reactions. METHODS: Twenty-one allergic asthmatic and six healthy control subjects underwent inhaled antigen challenge with measurements of plasma cortisol and cortisone by gas chromatography-mass spectrometry. RESULTS: There were no differences between the asthmatic and control groups in the baseline levels of cortisol or cortisone. However, the asthmatic subjects had significantly higher cortisol levels (67.2 +/- 8.6 vs 35.1 +/- 4.5 ng/mL; P = 0.04) and had higher cortisol/cortisone ratios (4.8 +/- 0. 6 vs 3.0 +/- 0.2; P = 0.01) 8 h after challenge compared to the control subjects. Among the asthmatic subjects, those whose FEV1 recovered rapidly had higher baseline levels of cortisol and those who displayed a late phase reaction had lower levels of cortisol during the late phase period. CONCLUSION: The results suggest that endogenous glucocorticoids may play a significant role in the modulation of airway responses to antigen challenge, and that antigen challenge may induce cortisol production in allergic subjects.
Notes: Journal Article
Author Address: Department of Medicine, Division of Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Title: Glucocorticoids and Immune Function
Author: Rook, G. A.; (Date: Dec, 1999)
Journal: Baillieres Best Pract Res Clin Endocrinol Metab; V. 13; Issue: 4; Pages: 567-81
Abstract: The prevailing notion has been that cytokines such as interleukin-1 released from sites of inflammation cross the blood-brain barrier and drive the hypothalamo-pituitary-adrenal (HPA) axis so that cortisol is released into the circulation to exert indiscriminate systemic anti-inflammatory effects. It is now clear that feedback from the HPA axis is subject to more subtle and localized regulation. The signal that activates cortisol release travels to the hypothalamus via vagal sensory afferents (so the brain ‘knows’ where the inflammation is), and the effects of the released cortisol are regulated within individual tissues via numerous mechanisms, including changes in the affinity of the cortisol receptors, and changes in the equilibrium point of the cortisol/cortisone shuttle (11 beta hydroxysteroid dehydrogenases 1 and 2). This equilibrium is locally regulated by cytokines. These mechanisms are central to the regulation of the balance of Th1 to Th2 cytokines within sites of inflammation, and to the appropriate or inappropriate termination of the inflammatory response in infections or autoimmunity.
Notes: Journal Article
Review
Review, Tutorial
Author Address: Department of Bacteriology, University College London Medical School, Windeyer Institute, UK.
Title: Glucocorticoid Regulation of Inflammation: The Plot Thickens
Author: Morand, E. F.; Leech, M.; (Date: Nov, 1999)
Journal: Inflamm Res; V. 48; Issue: 11; Pages: 557-60
Abstract: While glucocorticoids are widely used in the suppression of immune-inflammatory diseases, much remains unknown about the contribution of endogenous adrenal glucocorticoids to inflammatory regulation. It is now well understood that glucocorticoids are increased by inflammatory stress and provide for responsive limitation of inflammation. It is self-evident that the immune response in healthy animals takes place in a milieu characterised by background levels of glucocorticoids. It is less well appreciated, however, that basal levels of glucocorticoids may in fact be a requirement for a normal immune response. In fact, extensive data exist supporting the hypothesis that glucocorticoids interact with the immune-inflammatory system in a biphasic, concentration dependent fashion. No mechanistic explanation for this apparent paradox has previously existed. Recently, the cytokine macrophage migration inhibitory factor (MIF), while possessing pleiotropic pro-inflammatory properties, has been demonstrated to be glucocorticoid-inducible. This observation has the potential to explain key aspects of the biphasic regulation of inflammatory response by endogenous glucocorticoids.
Notes: Journal Article
Review
Review, Tutorial
Author Address: Centre for Inflammatory Diseases, Monash University, Dept of Medicine, Monash Medical Centre, Melbourne, Australia.
Title: Is Low Endogenous Cortisol a Risk Factor for Asthma?
Author: Kauffmann, F.; Guiochon-Mantel, A.; Neukirch, F.; (Date: Oct, 1999)
Journal: Am J Respir Crit Care Med; V. 160; Issue: 4; Pages: 1428
Notes: Comment
Letter
Title: Chronic Inflammatory Stress
Author: Harbuz, M. S.; (Date: Dec, 1999)
Journal: Baillieres Best Pract Res Clin Endocrinol Metab; V. 13; Issue: 4; Pages: 555-65
Abstract: A major mechanism involved in maintaining homeostasis in response to chronic inflammation is the hypothalamo-pituitary-adrenal (HPA) axis, resulting in the release of anti-inflammatory glucocorticoids from the adrenal cortex. An inadequate HPA axis response may result in the development of a pathology or an increase in susceptibility and/or severity of disease. Other neuroendocrine systems are also implicated. Increasingly considered important are circadian rhythms, not only of hormones, but also of components of the immune system. Recent evidence concerning changes in hypothalamic control of the HPA axis following development of disease, the implication of these for the response to stress and the use of the HPA axis as a predictor of susceptibility to disease will also be considered. Finally, the influence of stress on autoimmune disease will be discussed. This chapter will concentrate principally on rheumatoid arthritis, although other autoimmune diseases and animal models will be discussed.
Notes: Journal Article
Review
Review, Tutorial
Author Address: University Research Centre for Neuroendocrinology, University of Bristol, UK.
Title: Relationship of Dehydroepiandrosterone and Cortisol in Disease
Author: Hechter, O.; Grossman, A.; Chatterton, R. T., Jr.; (Date: Jul, 1997)
Journal: Med Hypotheses; V. 49; Issue: 1; Pages: 85-91
Abstract: Does dehydroepiandrosterone act as an adrenal hormone in humans to maintain cortisol homeostasis by serving as a cortisol antagonist? If so, dehydroepiandrosterone might block the development of the diverse pathological processes potentiated by prolonged cortisol hyperactivity. And the plasma concentrations of total dehydroepiandrosterone and total cortisol, expressed as a C/D ratio, would have an important influence on the development of age-related pathology in diseases exacerbated by cortisol hyperactivity. Several major age-related diseases, designated as cortisol-potentiated diseases, belong in this category. The C/D concept predicts, other factors being equal, that the risk of initiation and progression of these diseases at all ages is directly related to the C/D ratio, individuals with elevated C/D ratios being at high risk.
Notes: Journal Article
Author Address: Department of Physiology, Northwestern University Medical School, Chicago, IL 60615, USA.
Title: Hypothalamic-Pituitary-Adrenal Axis in Corticosteroid-Resistant Bronchial Asthma
Author: Lane, S. J.; Atkinson, B. A.; Swaminathan, R.; Lee, T. H.; (Date: Feb, 1996)
Journal: Am J Respir Crit Care Med; V. 153; Issue: 2; Pages: 557-60
Abstract: We have examined whether the lack of clinical response to corticosteroids seen in corticosteroid resistant (CR) bronchial asthma is reflected in abnormalities of endogenous cortisol secretion and in the sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis in CR subjects by using a modification of the standard dexamethasone suppression test (DST) in response to 0.25 and 1 mg oral dexamethasone. Five corticosteroid-sensitive (CS) and five CR asthmatic subjects were studied on two occasions 1 mo apart. In the first limb of the study subjects received 0.25 mg of oral dexamethasone, and in the second limb they received 1 mg. Urinary cortisol was measured by fluorimetry after extraction, and plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations were estimated by enzyme-linked immunosorbent assay (ELISA) and immunoradiometric assays, respectively. On Day 1, a 24-h urine sample was collected for estimation of urinary free cortisol. On Day 2, a fasting blood sample was taken at 9:00 A.M. for estimation of plasma cortisol and ACTH. At 11:00 P.M., 0.25 mg (1 mg) of dexamethasone was taken orally by each subject. On Day 3, blood was taken at 9:00 A.M. and 3:00 P.M. for similar estimations. The levels of urinary free cortisol (nmol/24 h) and predose plasma ACTH (ng/L) and cortisol (nmol/L) were 199 +/- 42, 27.4 +/- 5.7, and 300 +/- 48 (mean +/- SEM), respectively, in the CS group, and 210 +/- 74, 23.4 +/- 6.7, and 263 +/- 32 (mean +/- SEM), respectively, in the CR group (p > 0.05 for all comparisons). Plasma ACTH and cortisol concentrations were not significantly suppressed in either group after 0.25 mg dexamethasone, but were equally suppressed in both groups to undetectable levels by 1 mg dexamethasone. We conclude that CR asthma is not reflected in an altered secretory rate of endogenous cortisol or in an altered sensitivity of the HPA axis to dexamethasone suppression.
Notes: Journal Article
Author Address: Department of Allergy and Respiratory Medicine, Guy’s Hospital, London, United Kingdom.
Title: Low Serum Levels of Dehydroepiandrosterone May Cause Deficient Il-2 Production by Lymphocytes in Patients with Systemic Lupus Erythematosus (Sle)
Author: Suzuki, T.; Suzuki, N.; Engleman, E. G.; Mizushima, Y.; Sakane, T.; (Date: Feb, 1995)
Journal: Clin Exp Immunol; V. 99; Issue: 2; Pages: 251-5
Abstract: The principal cause of IL-2 deficiency, a common feature of both murine lupus and human SLE, remains obscure. Recent studies of our own as well as others have shown that dehydroepiandrosterone (DHEA), an intermediate compound in testosterone synthesis, significantly up-regulates IL-2 production of T cells, and that administration of exogenous DHEA or IL-2 via a vaccinia construct to murine lupus dramatically reverses their clinical autoimmune diseases. Thus, we have examined serum levels of DHEA in patients with SLE to test whether abnormal DHEA activity is associated with IL-2 deficiency of the patients. We found that nearly all of the patients examined have very low levels of serum DHEA. The decreased DHEA levels were not simply a reflection of a long term corticosteroid treatment which may cause adrenal atrophy, since serum samples drawn at the onset of disease, which are devoid of corticosteroid treatment, also contained low levels of DHEA. In addition, exogenous DHEA restored impaired IL-2 production of T cells from patients with SLE in vitro. These results indicate that defects of IL-2 synthesis of patients with SLE are at least in part due to the low DHEA activity in the serum.
Notes: Journal Article
Author Address: Department of Immunology, St. Marianna University School of Medicine, Kanagawa, Japan.
Title: Mechanism of Mast Cell Activation
Author: Peters, SP
Year: 1995
Series Editor: Holgate, Busse and
Series Title: Blackwell Scientific Publications
Volume: Asthma and Rhinitis
Number of Pages: 221-230
Title: Dehydroepiandrosterone (Dhea)–the “Mother Steroid”. I. Immunologic Action
Author: Regelson, W.; Loria, R.; Kalimi, M.; (Date: May 31, 1994)
Journal: Ann N Y Acad Sci; V. 719; Pages: 553-63
Notes: Journal Article
Review
Review, Tutorial
Author Address: Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Title: Case Report: Amelioration of Insulin Resistance in Diabetes with Dehydroepiandrosterone
Author: Buffington, C. K.; Pourmotabbed, G.; Kitabchi, A. E.; (Date: Nov, 1993)
Journal: Am J Med Sci; V. 306; Issue: 5; Pages: 320-4
Abstract: In hyperandrogenic females, the ratio of dehydroepiandrosterone (DHEA) to testosterone may be an important determinant of insulin sensitivity. This study involved changes in insulin sensitivity and glucose metabolism with therapeutic manipulation of DHEA (S)/testosterone in a female patient with non-insulin-dependent diabetes and hyperandrogenism. Therapeutic intervention included 1-month treatment with 0.25 mg dexamethasone at bedtime and 1-month dexamethasone + DHEA. Insulin sensitivity and glucose tolerance were assessed before and after each treatment regimen by examining: 1) fasting and oral glucose tolerance test glucose and insulin levels, 2) hypoglycemic response to intravenous insulin, and 3) erythrocyte insulin receptor binding. With dexamethasone alone, DHEAS, testosterone, and their ratio were reduced with a concomitant increase (30%) in oral glucose tolerance test insulin levels and a decrease (33%) in erythrocyte insulin binding. With DHEA + dexamethasone, the ratio of DHEAS/testosterone increased 16-fold along with a marked improvement in insulin sensitivity, as determined by a more than 30% reduction in fasting and oral glucose tolerance test insulin levels, a threefold stimulation of the rate of glucose disappearance with intravenous insulin, and a 30% increase in insulin binding. DHEA improved insulin sensitivity and reduced fasting and oral glucose tolerance test glucose levels and ameliorated the diabetic state. The ratio of DHEAS/testosterone is an important regulator of insulin sensitivity and glucose tolerance and that DHEA therapy may be beneficial in the treatment of certain forms of insulin resistance.
Notes: Journal Article
Author Address: Department of Medicine, University of Tennessee, Memphis.
Title: Elevated Serum Dehydroepiandrosterone Sulfate Levels in Practitioners of the Transcendental Meditation (Tm) and Tm-Sidhi Programs
Author: Glaser, J. L.; Brind, J. L.; Vogelman, J. H.; Eisner, M. J.; Dillbeck, M. C.; Wallace, R. K.; Chopra, D.; Orentreich, N.; (Date: Aug, 1992)
Journal: J Behav Med; V. 15; Issue: 4; Pages: 327-41
Abstract: Serum dehydroepiandrosterone sulfate (DHEA-S) levels were measured in 270 men and 153 women who were experienced practitioners of the Transcendental Meditation (TM) and TM-Sidhi programs, mental techniques practiced twice daily, sitting quietly with the eyes closed. These were compared according to sex and 5-year age grouping to 799 male and 453 female nonmeditators. The mean DHEA-S levels in the TM group were higher in all 11 of the age groups measured in women and in 6 of 7 5-year age groups over 40 in men. There were no systematic differences in younger men. Simple regression using TM-group data revealed that this effect was independent of diet, body mass index, and exercise. The mean TM-group levels measured in all women and in the older men were generally comparable to those of nonmeditator groups 5 to 10 years younger. These findings suggest that some characteristics of TM practitioners are modifying the age-related deterioration in DHEA-S secretion by the adrenal cortex.
Notes: Journal Article
Author Address: Department of Physiological and Biological Sciences, Maharishi International University, Fairfield, Iowa 52556.
Title: Natural Regulators of T-Cell Lymphokine Production in Vivo
Author: Daynes, R. A.; Araneo, B. A.; (Date: Oct, 1992)
Journal: J Immunother; V. 12; Issue: 3; Pages: 174-9
Abstract: The mammalian immune system possesses the intrinsic capacity to evoke a wide variety of functionally distinct effector mechanisms following stimulation by a particular antigenic substance. Such diversity in available responses is absolutely essential to the immunocompetent host, which must continually deal with a diverse set of potential pathogens within its ever-changing environment. The development of appropriate types of immune responses, therefore, represents a highly dynamic process that requires that an equivalent consideration be given to a large array of components, any one of which is capable of modulating the final outcome. While the nature and complexity of the antigen(s), plus the intracellular or extracellular mode of presentation, provide specificity and some selection to the developing process, the route of antigen entry, as well as the physiological status of the host at the time of antigen insult, also contribute significantly to the formation of any immune response. The overall objective of this article is to introduce the concept that platelet-derived growth factor (PDGF) (either preformed or synthesized in response to stimulation), plus a number of steroid hormones (some of which are end-organ metabolized at local tissue sites), can all play significant roles in the genesis of immunologic responses in vivo.
Notes: Journal Article
Author Address: Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132.
Title: Dehydroepiandrosterone Enhances Il2 Production and Cytotoxic Effector Function of Human T Cells
Author: Suzuki, T.; Suzuki, N.; Daynes, R. A.; Engleman, E. G.; (Date: Nov, 1991)
Journal: Clin Immunol Immunopathol; V. 61; Issue: 2 Pt 1; Pages: 202-11
Abstract: Dehydroepiandrosterone (DHEA) is the most abundant adrenal steroid hormone in humans. Although it is well established that DHEA serves as an intermediate in sex steroid synthesis, recent studies in mice suggest that DHEA may also be a physiologic regulator of IL2 secretion. To explore the effect of DHEA on the human immune system, T lymphocytes from healthy adults were exposed to DHEA followed by stimulation with mitogens or antigen. Upon activation with a variety of stimuli, T cells pretreated with 10(-8) to 10(-11) M DHEA produced significantly greater amounts of IL2 and mediated more potent cytotoxicity than T cells activated in the absence of this steroid hormone. The peak effect of DHEA was observed at 10(-9) M, the concentration of hormone present in the blood of normal adults. In contrast to its effect on murine T cells, the IL2 enhancing effect of DHEA on human lymphocytes was limited to fresh CD4+ T cells and CD4+ clones; neither fresh CD8+ cells nor CD8+ clones were directly affected by DHEA treatment, although CD8+ cells stimulated in the presence of CD4+ cells and DHEA demonstrated enhanced cytotoxicity. The enhancing effect of DHEA was also detected at the level of IL2 mRNA, suggesting that DHEA may act as a transcriptional enhancer of the IL2 gene in CD4+ T cells. These results corroborate and extend earlier studies in mice and suggest a physiologic role for DHEA in regulating the human immune response.
Notes: Journal Article
Author Address: Department of Pathology, Stanford University School of Medicine, California 94305.
Title: Cortisol and Immunity
Author: Jefferies, W. M.; (Date: Mar, 1991)
Journal: Med Hypotheses; V. 34; Issue: 3; Pages: 198-208
Abstract: The relationship between adrenocortical function and immunity is a complex one. In addition to the well-known detrimental effects of large, pharmacologic dosages of glucocorticoids upon the immune process, there is impressive evidence that physiologic amounts of cortisol, the chief glucocorticoid normally produced by the human adrenal cortex, is necessary for the development and maintenance of normal immunity. This evidence is reviewed, and the importance of differentiating between physiologic and pharmacologic dosages and effects is discussed. The popular use of synthetic derivatives of cortisol, which differ greatly from the natural hormone in strength, and the dynamic nature of the normal adrenocortical response, which varies with the degree of stress being experienced, have contributed to the confusion. Further studies of the nature of the beneficial effect of cortisol, and possibly of other normal adrenocortical hormones, upon immunity in humans are needed, especially in view of recent evidence of a feedback relationship between the immune system and the hypothalamic-pituitary-adrenal axis, and with the increasing awareness not only that the immune process provides protection against infection, but also that its impairment seems to be involved in the development of autoimmune disorders, malignancies and the acquired immunodeficiency syndrome (AIDS).
Notes: Journal Article
Review
Review, Tutorial
Title: Regulation of Murine Lymphokine Production in Vivo. Ii. Dehydroepiandrosterone Is a Natural Enhancer of Interleukin 2 Synthesis by Helper T Cells
Author: Daynes, R. A.; Dudley, D. J.; Araneo, B. A.; (Date: Apr, 1990)
Journal: Eur J Immunol; V. 20; Issue: 4; Pages: 793-802
Abstract: Dehydroepiandrosterone (DHEA) is an adrenal steroid hormone produced in abundance by humans and most other warm-blooded animals, is uniquely sulfated (DHEAS) prior to export into the plasma, and exhibits an age-related decline in production with progressive age. No major physiological functions have been ascribed to the activity of this steroid, although DHEA is known to serve as an intermediary in sex steroid synthesis. Studies on the effects of glucocorticoids (GCS) on the immune system led us to question whether DHEA had effects on the ability of activated lymphocytes to produce interleukin 2 (IL 2). We determined that (a) lymphocytes from DHEA- or DHEAS-treated mice consistently produced much greater levels of IL 2 than normals in response to stimulation, (b) direct lymphocyte exposure to DHEA at low doses (10(-10)-10(-7) M) caused an enhanced capacity to secrete IL 2 following activation, (c) IL 2 production by activated cloned T cell lines could be augmented by DHEA treatment, and (d) GCS-induced depressions in IL 2 synthesis by T cells or T cell clones could be overcome in vitro and in vivo by exposure to the effects of DHEA. These findings suggest that DHEA, presumably through receptor-mediated mechanisms similar to other types of steroid hormones, may represent a natural and important regulator of IL 2 production in both normal and pathologic conditions.
Notes: Journal Article
Author Address: Division of Cell Biology and Immunology, University of Utah School of Medicine, Salt Lake City 84132.
Title: Dehydroepiandrosterone Reduces Serum Low Density Lipoprotein Levels and Body Fat but Does Not Alter Insulin Sensitivity in Normal Men
Author: Nestler, J. E.; Barlascini, C. O.; Clore, J. N.; Blackard, W. G.; (Date: Jan, 1988)
Journal: J Clin Endocrinol Metab; V. 66; Issue: 1; Pages: 57-61
Abstract: To assess the effects of dehydroepiandrosterone (DHEA) on body fat mass, serum lipid levels, and tissue sensitivity to insulin, five normal men were given placebo and five normal men were given oral DHEA [1600 mg/day (554.7 mmol/day)] for 28 days in a randomized, double blind study. In the DHEA group serum DHEA-S levels rose 2.5- to 3.5-fold, and mean (+/- SEM) serum androstenedione rose from 4.3 +/- 0.6 to 8.6 +/- 1.2 nmol/L (P less than 0.004, by paired t test), but serum total testosterone, free testosterone, sex hormone-binding globulin, estradiol, and estrone levels did not change. In the DHEA group the mean percent body fat decreased by 31%, with no change in weight. This suggests that the reduction in fat mass was coupled with an increase in muscle mass. DHEA administration also resulted in a fall in mean serum total cholesterol concentration (4.82 +/- 0.21 vs. 4.48 +/- 0.29 nmol/L; P less than 0.05), which was due almost entirely to a fall of 7.5% in mean serum low density lipoprotein cholesterol (3.21 +/- 0.11 vs. 2.97 +/- 0.14 nmol/L; P less than 0.01). No changes in anthropometric parameters or serum lipid levels occurred in the placebo group. Tissue sensitivity to insulin, assessed by the hyperinsulinemic-euglycemic clamp technique, did not change in either the placebo or DHEA groups. These results suggest that in normal men DHEA administration reduces body fat, increases muscle mass, and reduces serum low density lipoprotein cholesterol levels. Tissue sensitivity to insulin was unaffected by short term DHEA administration.
Notes: Clinical Trial
Journal Article
Randomized Controlled Trial
Author Address: Division of Endocrinology and Metabolism, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.