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PubMedDate not supplied

Correlation between increased cortisol:DHEA ratio and malnutrition in HIV-positive men.

Malnutrition in HIV-infected patients is characterized by a loss of both fat-free mass (FFM) and fat mass (FM). Glucocorticoids and androgens change during the course of the infection and may play a key role in the protein balance. The serum concentrations of cortisol, adrenal (DHEA and DHEA sulfate) and gonadal androgens (androstenedione, testosterone, and dihydrotestosterone) of HIV-positive men were measured and compared with several parameters of body composition as a function of body weight loss (BWL). The patients were assigned to one of five groups according to their BWL: group I (controls, n = 10) < 5%, group II (n = 7) 5-10%, group III (n = 8) 10.1-16%, group IV (n = 9) 16.1-24%, and group V (n = 4) > 24.1%. Correlation analysis showed significant positive or negative relationships between several markers of malnutrition and adrenal androgens and the cortisol:DHEA ratio, but not with cortisol. BWL was negatively correlated with DHEA (r = -0.69, P < 0.0001), DHEA sulfate (r = -0.58, P < 0.0001) and testosterone (r = -0.34, P < 0.03), but positively with the cortisol:DHEA ratio (r = 0.61, P < 0.0001). In contrast, BCM was positively correlated with DHEA (r = 0.34, P < 0.04) and DHEA sulfate (r = 0.36, P < 0.03) and negatively with the cortisol:DHEA ratio (r = -0.58, P < 0.0001). The cortisol:DHEA ratio was also negatively correlated with BMI (body mass index) (r = -0.56, P < 0.01), fat-free mass (r = -0.48, P < 0.004), fat mass (r = -0.39, P < 0.02), and BCM:weight ratio (r = -0.47, P < 0.005) and positively with the extracellular:intracellular water ratio (r = 0.54, P < 0.001). These data indicate that the steroid hormone environment of patients, particularly their cortisol:DHEA ratio, is linked to the malnutrition associated with HIV infection. The decreased DHEA and increased cortisol in patients with the advanced stages of disease could be associated with increased protein catabolism.

Adult↗

PubMed2002

Longitudinal evolution of HIV-1-associated lipodystrophy is correlated to serum cortisol:DHEA ratio and IFN-alpha.

BACKGROUND: We have previously shown that lipid alterations in HIV-1-associated lipodystrophy (LD) are correlated with decreased serum dehydroepiandosterone (DHEA) and increased cortisol:DHEA ratio and IFN-alpha levels. OBJECTIVE: To evaluate in a longitudinal study whether steroid and cytokine modifications are associated with the evolution of physical changes and lipid alterations associated with LD. METHODS: Thirty-four HIV-1-positive men were followed during 32.5 +/- 4.0 months and tested at four time-points. The patients were subdivided into five groups according to physical changes and anthropometric measurements: LD-negative, initially LD-negative becoming LD-positive, LD-positive unchanged, aggravated or improved. Serum lipids, apolipoproteins, adrenal steroids and cytokines were measured and compared with baseline values. RESULTS: (1) LD aggravation is associated with persistent elevated lipids, a decrease in serum DHEA, an increase in cortisol:DHEA ratio and persistent high levels of IFN-alpha. (2) LD improvement is associated with normalization of serum lipids, an increase in serum DHEA leading to normalization in cortisol:DHEA ratio, and normalization of IFN-alpha levels. (3) In LD-positive men evolution of VLDL cholesterol is negatively correlated with DHEA (r = -0.56, P < 0.01) and positively with cortisol:DHEA ratio (r = 0.62, P < 0.004) and with IFN-alpha (r = 0.57, P < 0.01). (4) The switch to LD is associated with a decrease in serum DHEA. (5) Patients who remained LD-negative maintained normal lipids, elevated cortisol and DHEA, and normal cortisol:DHEA ratio and normal levels of IFN-alpha. CONCLUSIONS: This study indicates that cortisol:DHEA ratio and serum IFN-alpha levels are closely associated with clinical evolution and atherogenic lipid alterations in LD.

Adult↗

PubMed2002

Acute dehydroepiandrosterone (DHEA) effects on sexual arousal in postmenopausal women.

BACKGROUND: The age-related decline of dehydroepiandrosterone (DHEA) has prompted research on its experimental replacement in women. Although no relationship to sexual functioning in healthy women has been shown to date, DHEA replacement has potential for affecting sexual response. METHODS: To investigate DHEA effects, 16 sexually functional postmenopausal women participated in a randomized, double-blind, crossover protocol in which oral administration of DHEA (300 mg) or placebo occurred 60 minutes before the presentation of an erotic video segment. Blood DHEA sulfate (DHEAS) changes, subjective and physiological sexual responses, as well as affective responses were measured in response to videotaped neutral and erotic video segments. RESULTS: The concentration of DHEAS increased 2-5-fold following DHEA administration in all 16 women. Subjective ratings across DHEA and placebo conditions showed significantly greater mental (p < 0.016) and physical (p < 0.036) sexual arousal to the erotic video with DHEA vs. placebo. Positive affect also increased during the erotic video across drug conditions. Vaginal pulse amplitude (VPA) and vaginal blood volume (VBV) demonstrated a significant increase (p < 0.001) between neutral and erotic film segments within both conditions (DHEA and placebo) but did not differentiate drug conditions. CONCLUSION: In sum, increases in mental and physical sexual arousal ratings significantly increased in response to an acute dose of DHEA in postmenopausal women.

Administration, Oral↗

PubMed1993

Vitamin E alters hepatic antioxidant enzymes in rats treated with dehydroepiandrosterone (DHEA).

The effects of vitamin E on hepatic antioxidant enzymes and plasma indicators of tissue damage were studied in rats treated with dehydroepiandrosterone (DHEA). Thirty-two male Sprague-Dawley rats were randomly allotted to one of four groups of eight rats each. Rats were treated with DHEA [100 mg/(kg body wt.d), i.p.], vitamin E (1 g/kg diet), or DHEA+vitamin E, or were untreated (controls) for 5 wk. Treatment with DHEA reduced (P < 0.05) weight gain, fat pad weight and carcass lipid concentration and increased carcass protein and ash concentration compared with control rats. The DHEA-treated rats had significantly lower concentrations of serum triglycerides and total cholesterol, yet greater amounts of liver lipid, than did control rats. Supplementation of DHEA-treated rats with vitamin E had no significant effect on weight gain, carcass composition or plasma metabolites compared with rats treated with DHEA alone. The rate of hepatic peroxisomal fatty acid oxidation in DHEA-treated rats was approximately 240% of that in control or vitamin E-supplemented rats. The specific activities of enzymes that defend against oxidative stress (e.g., glutathione reductase, glutathione transferase, catalase) or are indicators of tissue damage (e.g., alanine and aspartate aminotransferases) were all significantly higher in DHEA-treated rats compared with control rats. Supplementation of DHEA-treated rats with vitamin E generally reduced these indices of oxidative stress compared with rats treated with DHEA alone, suggesting that vitamin E may have a protective effect against potential oxidative damage associated with DHEA treatment.

Animals↗

PubMed1997

The effect of DHEAS on influenza vaccination in aging adults.

OBJECTIVE: To determine whether simultaneous administration of dehydroepiandrosterone sulfate (DHEAS) exhibits adjuvant activity in the immune response of aging humans by supplementing influenza vaccination with the maximum single dose of DHEAS that could be practically injected subcutaneously (approximately 7.5 mg). DESIGN: A randomized, double-blind, placebo-controlled trial of DHEAS injection with 1993-94 and 1994-95 influenza vaccine in older subjects. In addition, initial safety, tolerability, and control testing with 1993-94 influenza vaccine was conducted in young subjects. SETTING: An urban primary care geriatrics clinic. PARTICIPANTS: Seventy-eight older adult volunteers (mean age 78.61 +/- 3.43 years, range 73-90 years) and 20 younger controls (< 40 years, means age 32.76 +/- 5.39 years) were recruited from clinic and community advertising. Subjects were free of disease or medication known to affect immune function. MEASUREMENTS: Immune responses to vaccine at 0, 2, and 4 weeks were measured by vaccine antigen-induced lymphoproliferation in peripheral blood mononuclear cells (PBMC) and serum antibody response by hemagglutination inhibition (HI). RESULTS: The maximum DHEAS dose that could be practically administered subcutaneously was 7.5 mg. Baseline DHEAS levels were significantly lower in older adults (52.1 vs 236.4 micrograms/dL, P < .001). The 1993 old adult DHEAS group HI response tended to be higher for the H3N2 Beijing antigen but not for the H1N1 or B antigen. In subjects with HI titers less then 1:40 for the H3N2 Beijing antigen (n = 29), the post-vaccination titer response tended to be higher among the 16 subjects who received DHEAS (P = .06). The peak response for the H3N2 antigen was associated with the initial DHEAS serum concentration in the DHEAS and placebo groups (R2 = .22, P = .04 and R2 = .21, P = .06, respectively). No significant differences were found for antibody responses to the H1N1 and B antigens or vaccine-antigen induced lymphoproliferation. CONCLUSION: A one-time supplemental dose of DHEAS with influenza vaccination appeared to enhance the specific HI antibody response to the 1993-94 H3N2 antigen in a small group of older adults. These findings were limited to those with lower prevaccination titers and lower DHEAS concentrations. Although clinical implications of these findings for influenza vaccine are uncertain, these results suggest additional detailed immunologic investigations on the role of DHEAS in the aging human immune response are warranted.

Adult↗

PubMed2004

Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial.

CONTEXT: Dehydroepiandrosterone (DHEA) administration has been shown to reduce accumulation of abdominal visceral fat and protect against insulin resistance in laboratory animals, but it is not known whether DHEA decreases abdominal obesity in humans. DHEA is widely available as a dietary supplement without a prescription. OBJECTIVE: To determine whether DHEA replacement therapy decreases abdominal fat and improves insulin action in elderly persons. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted in a US university-based research center from June 2001 to February 2004. PARTICIPANTS: Fifty-six elderly persons (28 women and 28 men aged 71 [range, 65-78] years) with age-related decrease in DHEA level. INTERVENTION: Participants were randomly assigned to receive 50 mg/d of DHEA or matching placebo for 6 months. MAIN OUTCOME MEASURES: The primary outcome measures were 6-month change in visceral and subcutaneous abdominal fat measured by magnetic resonance imaging and glucose and insulin responses to an oral glucose tolerance test (OGTT). RESULTS: Of the 56 men and women enrolled, 52 underwent follow-up evaluations. Compliance with the intervention was 97% in the DHEA group and 95% in the placebo group. Based on intention-to-treat analyses, DHEA therapy compared with placebo induced significant decreases in visceral fat area (-13 cm2 vs +3 cm2, respectively; P = .001) and subcutaneous fat (-13 cm2 vs +2 cm2, P = .003). The insulin area under the curve (AUC) during the OGTT was significantly reduced after 6 months of DHEA therapy compared with placebo (-1119 muU/mL per 2 hours vs +818 muU/mL per 2 hours, P = .007). Despite the lower insulin levels, the glucose AUC was unchanged, resulting in a significant increase in an insulin sensitivity index in response to DHEA compared with placebo (+1.4 vs -0.7, P = .005). CONCLUSION: DHEA replacement could play a role in prevention and treatment of the metabolic syndrome associated with abdominal obesity.

Abdomen↗

PubMed1996

Serum dehydroepiandrosterone and DHEA-sulfate in patients with adult T-cell leukemia and human T-lymphotropic virus type I carriers.

The serum levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) were determined by radioimmunoassay in 38 patients with adult T-cell leukemia (ATL). Levels of serum DHEA and DHEA-S were also measured in 60 human T-lymphotropic virus type I (HTLV-I) carriers, and did not differ from those in 60 healthy control subjects. Serum levels in patients with ATL were lower than those in the age- and sex-matched healthy controls and in HTLV-I carriers with statistical significance. Serum DHEA and DHEA-S in male patients with acute and lymphoma-type ATL were 1.06 +/- 0.77 ng/ml and 245.8 +/- 192.9 ng/ml, respectively. Levels in male patients with chronic and smoldering-type ATL were 1.69 +/- 0.68 ng/ml and 477.6 +/- 251.5 ng/ml, respectively. Serum levels of DHEA and DHEA-S in patients with acute and lymphoma-type ATL were significantly lower than those in patients with chronic and smoldering-type ATL (P < 0.05). These data suggest that a decrease in serum levels of DHEA and DHEA-S may be associated with patients who have some clinical subtypes of ATL. Moreover, androgens may have a therapeutic role in patients with ATL, as administered in patients with hairy-cell leukemia. Because there is at present no curative chemotherapy for ATL, a trial combination of androgens and standard chemotherapy may be a reasonable therapeutic option in such patients.

Adrenal Cortex↗

PubMed2002

Dehydroepiandrosterone (DHEA) increases territorial song and the size of an associated brain region in a male songbird.

In many species, male territorial aggression is tightly coupled with gonadal secretion of testosterone (T). In contrast, in song sparrows (Melospiza melodia morphna), males are highly aggressive during the breeding (spring) and nonbreeding (autumn and early winter) seasons, but not during molt (late summer). In aggressive nonbreeding song sparrows, plasma T levels are basal (< or = 0.10 ng/ml), and castration has no effect on aggression. However, aromatase inhibitors reduce nonbreeding aggression, indicating a role for estrogen in wintering males. In the nonbreeding season, the substrate for brain aromatase is unclear, because plasma T and androstenedione levels are basal. Aromatizable androgen may be derived from plasma dehydroepiandrosterone (DHEA), an androgen precursor. DHEA circulates at elevated levels in wintering males (approximately 0.8 ng/ml) and might be locally converted to T in the brain. Moreover, plasma DHEA is reduced during molt, as is aggression. Here, we experimentally increased DHEA in wild nonbreeding male song sparrows and examined territorial behaviors (e.g., singing) and discrete neural regions controlling the production of song. A physiological dose of DHEA for 15 days increased singing in response to simulated territorial intrusions. In addition, DHEA treatment increased the volume of a telencephalic brain region (the HVc) controlling song, indicating that DHEA can have large-scale neuroanatomical effects in adult animals. The DHEA treatment also caused a slight increase in plasma T. Exogenous DHEA may have been metabolized to sex steroids within the brain to exert these behavioral and neural effects, and it is also possible that peripheral metabolism contributed to these effects. These are the first results to suggest that exogenous DHEA increases male-male aggression and the size of an entire brain region in adults. The data are consistent with the hypothesis that DHEA regulates territorial behavior, especially in the nonbreeding season, when plasma T is basal.

Aggression↗

PubMed2004

IGF-I signaling prevents dehydroepiandrosterone (DHEA)-induced apoptosis in hypothalamic neurons.

Dehydroepiandrosterone (DHEA) is synthesized in the brain, but whether DHEA is involved in modulating neuronal cell survival is not yet fully understood. Herein we show that when deprived of trophic support, GT1-7 hypothalamic neurons undergo apoptosis following exposure to DHEA, as demonstrated both by morphological and biochemical criteria. This proapoptotic effect appeared to be specific to DHEA itself, and not through conversion of DHEA to other steroids such as androgen or estrogen. Importantly, we determined that IGF-I protects GT1-7 neurons from DHEA-induced cell death. DHEA-induced apoptosis was associated with increased activation of caspase 3 and decreased PARP, which were both attenuated with addition of IGF-I. Addition of DHEA prevented phosphorylation of both Akt and glycogen synthase kinase-3 beta (GSK-3beta), downstream effector molecules of the phosphatidylinositol 3-kinase (PI3K) pathway. Further IGF-I was able to sustain Akt activity and thus preventing GSK-3beta activation in the presence of DHEA. On the other hand, the MAP kinases, ERK, p38, and JNK, were not affected by DHEA. These findings suggest that in GT1-7 hypothalamic neurons, DHEA acts detrimentally to induce cell death and IGF-I is able to rescue the neurons by preserving the activity of Akt, and therefore maintaining the proapoptotic kinase GSK-3beta, in a phosphorylated catalytically inactive state.

Animals↗

PubMed2003

Evidence that dehydroepiandrosterone, DHEA, directly inhibits GnRH gene expression in GT1-7 hypothalamic neurons.

Dehydroepiandrosterone (DHEA) has been reported to have diverse effects on overall physiology, although its mechanism of action and specific receptor are not yet known. We have used the immortalized, clonal GT1-7 hypothalamic neurons to study DHEA effects on gonadotropin-releasing hormone (GnRH) gene expression. DHEA (10(-4) M) downregulates GnRH transcription by 39, 70 and 83% at 24, 36, and 48 h, respectively, while DHEA-sulphate had no effect. Hydroxyflutamide a specific androgen receptor (AR) antagonist, and cyproterone acetate or trilostane, both inhibitors of 3 beta-hydroxysteroid dehydrogenase/delta 4,5 isomerase, the rate-limiting enzyme for the conversion of DHEA to sex steroids, did not affect the ability of DHEA to downregulate GnRH gene expression. We found that GT1-7 cells did not express aromatase, thereby precluding conversion to estrogen. Analysis of [(14)C] DHEA metabolism by thin layer chromatography indicates that the main metabolites produced are 7 alpha- and 7 beta-hydroxy DHEA, and 7-oxo DHEA, although these steroids were not able to repress GnRH gene expression alone. Cell viability studies indicated that the transcriptional repression observed is not due to GT1-7 cell death. Interestingly, SV40 T-antigen mRNA levels, under the control of 2.3 kb of the rat GnRH gene 5' regulatory region, are also repressed by DHEA. Our studies indicate that DHEA has direct effects on GnRH transcription that appear to be unique from those observed after conversion to other steroidogenic compounds.

5' Untranslated Regions↗

PubMed1998

Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal women.

OBJECTIVES: A progressive decline of plasma dehydroepiandrosterone (DHEA) levels occurs in women during aging related to the reduction of adrenocortical secretion. A specific action of DHEA on the central nervous system (CNS) is suggested by the improvement of psychological and physical well-being in postmenopausal women after DHEA supplementation. The aim of the present study was to investigate the neuroendocrine effects of short-term DHEA supplementation in postmenopausal women, evaluating changes of plasma beta-endorphin (beta-EP) and growth hormone (GH) before and after oral DHEA (100 mg/day) for 7 days in postmenopausal women (n = 6). METHODS: Before and after 7 days of DHEA supplementation, postmenopausal women underwent a neuroendocrine test with clonidine, an alpha 2 presinaptic agonist for adrenergic system (1.25 mg i.v.). Basal plasma DHEA, androstenedione (A), testosterone (T), estrone (E1) and estradiol (E2) levels were evaluated before and after treatment, while plasma beta-EP and GH levels were measured before and 15, 30, 45, 60 and 90 min after clonidine injection. RESULTS: Basal plasma beta-EP and GH levels did not show a significant difference before and after short-term DHEA administration, while circulating A, T, E1 and E2 significantly increased after treatment. The clonidine test induced a significant increase of plasma beta-EP levels in women after receiving DHEA supplementation but not before; conversely, plasma GM levels increased both before and after treatment. CONCLUSIONS: The present study indicates that short-term DHEA supplementation in postmenopausal women is able to restore the impaired response of pituitary beta-EP to clonidine, an alpha 2 presinaptic agonist. According to these data it is possible to hypothesize that DHEA could play a role in the psychological and physical well-being of postmenopausal women acting via a restoration of neuroendocrine control of antero-pituitary beta-EP secretion.

Administration, Oral↗

PubMed2002

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.

Administration, Oral↗

PubMed2000

Oral dehydroepiandrosterone (DHEA) replacement therapy in women with Addison's disease.

OBJECTIVE: Patients with primary adrenocortical failure (Addison's disease) have abnormally low levels of DHEA and androgens relative to age. To define a suitable dose, the effect of oral dehydroepiandrosterone (DHEA) replacement therapy in women with Addison's disease (n = 9) was evaluated. DESIGN AND MEASUREMENTS: DHEA was administered as a daily oral dose of either 50 mg (n = 5) or 200 mg (n = 4). Blood sampling and measurements of insulin sensitivity (as measured with euglycemic insulin clamp technique) and body composition (as measured by dual energy X-ray absorptiometry) were performed before and during DHEA treatment and at a 3-month follow up. RESULTS: DHEA and DHEA(S) levels were restored to normal in those patients receiving 50 mg whereas DHEA(S) level was slightly above the normal reference value in those receiving 200 mg. Circulating levels of androgens (androstenedione, testosterone and testosterone/SHBG ratio) were normalized in all patients. A slight rise in IGF-1 levels was seen in both groups as was a decrease in the levels of low and high density lipoproteins. No effect on blood glucose levels or insulin sensitivity was seen and no change of body composition was observed. No serious side-effects were seen, but some of the patients experienced increased apocrine sweat secretion (n = 7), itchy scalp (n = 2) and acne (n = 7), all of which were reversed when DHEA was discontinued. CONCLUSION: A daily replacement dose of 50 mg of DHEA results in near physiological levels of DHEA, DHEA(S) androstenedione and testosterone in women with Addison's disease, without severe side-effects.

Addison Disease↗

PubMed2006

DHEAS levels and mortality in disabled older women: the Women's Health and Aging Study I.

BACKGROUND: Dehydroepiandrosterone sulfate (DHEAS) is an endogenously produced sex steroid that has been hypothesized to have anti-aging effects. Low DHEAS levels are associated with mortality in older men, but the relationship between DHEAS levels and mortality in women is not clearly defined. METHODS: The relationship between serum DHEAS level and 5-year mortality was analyzed in a cohort of 539 disabled women aged 65-100 years enrolled in the Women's Health and Aging Study I (WHAS I). Using Cox proportional hazard models, we calculated multivariate-adjusted mortality risks by DHEAS quartiles and by DHEAS continuously, allowing for a nonlinear relationship. We also examined cause-specific mortality. RESULTS: We found a U-shaped relationship between DHEAS level and mortality. After adjusting for multiple covariates, women in the top and bottom DHEAS quartiles had a more than 2-fold higher 5-year mortality than did those in the middle quartiles (hazard ratio, 2.15; 95% confidence interval [CI], 1.17-3.98 for the top quartile and 2.05; 95% CI, 1.27-3.32 for the bottom quartile, each compared to the third quartile). Women with higher DHEAS levels tended to have greater cancer mortality, whereas those with lower DHEAS tended to have greater cardiovascular mortality. CONCLUSION: Disabled older women with either low or high levels of DHEAS are at greater risk for death than are those with intermediate levels. More research is needed to determine if targeted dehydroepiandrosterone supplementation would provide clinical benefit to disabled older women.

Aged↗

PubMed2003

Influence of DHEA administration on 24-hour cortisol concentrations.

DHEA is marketed and readily available as a daily nutritional supplement to counteract the effects of aging. The effect of DHEA administration on 24-hour plasma cortisol profiles has not been investigated. In this single-blind placebo-controlled crossover study, the effect of DHEA administration on cortisol concentrations was evaluated in healthy older women and men. Once each morning, subjects took either placebo (Days 1 to 7, and 23 to 29) or oral DHEA 200 mg (Days 8 to 22: doses 1 to 15). Twenty-four hour DHEA and cortisol concentrations were measured on Day 1 (placebo), Day 8 (DHEA dose 1), Day 15 (DHEA dose 8), Day 22 (DHEA dose 15), and Day 29 (placebo washout dose 7). DHEA administration resulted in a decrease in plasma cortisol concentrations (mean, peak, and/or AUC) in healthy older women and men. The cortisol-lowering effect of DHEA was more pronounced in women than in men in our study; pairwise differences in concentrations between days showed that relative to Day 1, cortisol was lower on Days 15, 22, and 29 in women (p = 0.0001) and on Day 15 in men (p = 0.002). The mechanism by which DHEA lowers plasma cortisol concentrations merits further investigation.

Aged↗

PubMedDate not supplied

Hormonal profile effects following dehydroepiandrosterone (DHEA) administration to schizophrenic patients.

Dehydroepiandrosterone (DHEA) is an important neurosteroid and has demonstrated efficacy in the improvement of mood and energy. The authors previously reported the efficacy of DHEA augmentation in the management of negative, depressive, and anxiety symptoms of schizophrenia. To characterize further the effects of DHEA administration and to describe any hormonal effects following DHEA augmentation of antipsychotic medication, several hormones were measured (TSH, prolactin, testosterone, insulin, and estradiol) in 27 chronic schizophrenic inpatients receiving DHEA or placebo augmentation for 6 weeks. No significant changes in hormonal blood measures were noted. At the study end point, an association was noted between DHEA-S and TSH levels (P < 0.05) as well as a change in DHEA-S and insulin levels (P < 0.001). A modest nonsignificant decrease in plasma testosterone was observed following DHEA treatment. In subjects receiving DHEA, change in testosterone levels was associated with improvement in anxiety (P < 0.05) and illness severity (P < 0.05). Findings in this preliminary study demonstrate minimal effects on hormonal profiles despite the theoretic possibility that DHEA may elevate various hormones (eg, testosterone) with potential long-term adverse effects. DHEA's clinical efficacy appears to be mediated by other mechanisms, including direct effects on membrane channel-coupled receptors.

Adjuvants, Immunologic↗

PubMed1988

Effect of short-term DHEA administration on liver metabolism of lean and obese rats.

Lean and obese Zucker rats, 7-8 wk of age, were treated with dehydroepiandrosterone (DHEA) for either 3 or 7 days to determine the initial cellular event(s) that might be responsible for the antiobesity activity of DHEA. Epididymal, retroperitoneal, and brown adipose tissue weights were unaltered by either 3 or 7 days of DHEA treatment. Liver weight was not affected by 3 days of treatment but was 13 and 18% higher in 7-day DHEA-treated lean and obese rats, respectively, compared with their corresponding control group. Mitochondrial state 3 respiration rates with glutamate-malate and succinate as substrates were elevated by an average of 35% in 3- and 7-day DHEA-treated obese rats and by 15-20% in 7-day DHEA-treated lean rats compared with rates obtained in the corresponding control groups. State 3 respiration was not affected in 3-day DHEA-treated lean rats compared with control lean rats. The specific activities of long-chain fatty acyl-coenzyme A synthase and hydrolase and the levels of free CoA were increased by severalfold in cellular fractions of both DHEA-treated lean and obese rats compared with their respective control group. Hepatic malic enzyme activity, which was shown earlier to be elevated with long-term DHEA treatment, was unaltered by either 3 or 7 days of DHEA administration. The above results suggest the involvement of mitochondrial respiration and fatty acid deacylation/reacylation in the antiobesity mechanism of action of DHEA.

Adipose Tissue↗

PubMed1999

DHEA improves glucose uptake via activations of protein kinase C and phosphatidylinositol 3-kinase.

We have examined the effect of adrenal androgen, dehydroepiandrosterone (DHEA), on glucose uptake, phosphatidylinositol (PI) 3-kinase, and protein kinase C (PKC) activity in rat adipocytes. DHEA (1 microM) provoked a twofold increase in 2-[3H]deoxyglucose (DG) uptake for 30 min. Pretreatment with DHEA increased insulin-induced 2-[3H]DG uptake without alterations of insulin specific binding and autophosphorylation of insulin receptor. DHEA also stimulated PI 3-kinase activity. [3H]DHEA bound to purified PKC containing PKC-alpha, -beta, and -gamma. DHEA provoked the translocation of PKC-beta and -zeta from the cytosol to the membrane in rat adipocytes. These results suggest that DHEA stimulates both PI 3-kinase and PKCs and subsequently stimulates glucose uptake. Moreover, to clarify the in vivo effect of DHEA on Goto-Kakizaki (GK) and Otsuka Long-Evans fatty (OLETF) rats, animal models of non-insulin-dependent diabetes mellitus (NIDDM) were treated with 0.4% DHEA for 2 wk. Insulin- and 12-O-tetradecanoyl phorbol-13-acetate-induced 2-[3H]DG uptakes of adipocytes were significantly increased, but there was no significant increase in the soleus muscles in DHEA-treated GK/Wistar or OLETF/Long-Evans Tokushima (LETO) rats when compared with untreated GK/Wistar or OLETF/LETO rats. These results indicate that in vivo DHEA treatment can result in increased insulin-induced glucose uptake in two different NIDDM rat models.

Adipocytes↗