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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-2504
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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 8 4777-4783
Copyright © 2005 by The Endocrine Society

Effects of Dehydroepiandrosterone and Alprazolam on Hypothalamic-Pituitary Responses to Exercise

Patricia A. Deuster, Martha M. Faraday, George P. Chrousos and Merrily A. Poth

Departments of Military and Emergency Medicine (P.A.D.), Medical and Clinical Psychology (M.M.F.), and Pediatrics (M.A.P.), Uniformed Services University of the Health Sciences; Bethesda, Maryland 20814; and Pediatric and Reproductive Endocrinology Branch (G.P.C.), National Institute of Child Health and Human Development, Bethesda Maryland 20892

Address all correspondence and requests for reprints to: Patricia A. Deuster, Ph.D., MPH, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799. E-mail: pdeuster{at}usuhs.mil.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: The hypothalamic-pituitary-adrenal axis (HPA) is restrained by activation of {gamma}-amino-butyric acid receptors. Alprazolam (APZ) and dehydroepiandrosterone (DHEA) are purported to be {gamma}-amino-butyric acid agonists and antagonists, respectively.

Objective: Our objective was to examine the effects of APZ and DHEA alone and in combination on HPA axis activity.

Design: This was a double-blind, crossover, placebo-controlled study.

Setting: The study setting was the general community.

Participants: Subjects consisted of 15 men (age, 20–45 yr) with a body mass index of 20–25 kg/m2.

Interventions: DHEA (100 mg/d) or placebo was given for 4 wk, followed by a 2-wk washout; participants ingested 0.5 mg APZ or placebo 10 and 2 h before high-intensity exercise.

Outcome Measures: We measured basal and exercise-induced ACTH, arginine vasopressin (AVP), cortisol, DHEA, and GH responses. It was hypothesized that DHEA would enhance and APZ would blunt exercise-induced ACTH and cortisol release.

Results: DHEA significantly increased the AVP response to exercise (P < 0.01). APZ treatment significantly increased basal GH and blunted plasma cortisol, ACTH, AVP, and DHEA responses to exercise (P < 0.05). DHEA and APZ in combination significantly increased the GH response to exercise (P < 0.01).

Conclusions: DHEA may alter a subset of receptors involved in AVP release. Together DHEA and APZ may up-regulate GH during exercise by blunting a suppressive (HPA axis) and potentiating an excitatory (glutamate receptor) system.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
DEHYDROEPIANDROSTERONE (DHEA), A MAJOR adrenal hormone, and its conjugate, DHEA sulfate (DHEAS), are the most abundant adrenal steroid hormones in blood (1, 2, 3). Despite their abundance, all of their actions and functions have not been identified. It has become clear, however, that DHEA and DHEAS are active as neurosteroids and serve a variety of functions in the brain (1, 2, 3). Interestingly, these neurosteroids appear to act through both classic steroid hormone nuclear and nonnuclear receptor mechanisms (1). With respect to nonnuclear receptor actions, both DHEA and DHEAS have been reported to act at {gamma}-amino-butyric acid A (GABAA), N-methyl-D-aspartate (NMDA) and/or sigma receptors (1). In addition, DHEA and/or DHEAS may act as antagonists of glucocorticoids (4, 5).

We previously demonstrated that persons classified by their ACTH-releasing hormone and cortisol responses to exercise as high stress reactors exhibit significantly higher baseline concentrations of DHEA and DHEAS, compared with those classified as low stress reactors (6, 7). This finding suggested that DHEA might enhance the hypothalamic-pituitary-adrenal (HPA) axis response to exercise. One potential mechanism for increased HPA reactivity might be antagonism of the GABAA receptor because GABAergic activation restrains HPA axis activity (8, 9). In addition, GH and arginine vasopressin (AVP) secretions are markedly stimulated by exercise, and the literature also suggests GABAergic regulation of these hormones (10, 11, 12, 13, 14). In contrast to DHEA, alprazolam (APZ), a GABAA agonist, potentiates restraint of the HPA axis (15, 16, 17, 18, 19, 20, 21, 22).

The present study was designed to examine potential actions and interactions between GABAergic pathways and the hypothalamic response to exercise, using DHEA as a GABAergic antagonist and APZ as a GABAergic agonist. We addressed the following questions: 1) will chronic supplementation with DHEA alter the ACTH, cortisol, AVP, and GH responses to exercise; and 2) will acute pretreatment with APZ alone or in combination with DHEA restrain neuroendocrine responses to exercise?


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Participants

The Institutional Review Board of the Uniformed Services University of the Health Sciences approved the study, and all participants signed an informed consent document before participation. Healthy, nonsmoking, low to highly physically fit men (n = 15) between the ages of 20 and 45 yr and within 90–110% of their ideal weight and/or a body mass index between 20 and 25 kg/m2 were recruited to participate in the experiments outlined below. Participants were carefully screened (medical history, physical exam) by a physician before participation to rule out diabetes, chronic fatigue, fibromyalgia, a history of clinical depression, thyroid or other endocrine diseases, hypertension, cardiac disease, liver disease, and obesity. Subjects on chronic medications (including steroid inhalants or nasal sprays), those with any serious medical illness, or those already taking DHEA were excluded. In addition, all participants underwent a modified version of the structured psychiatric diagnostic interview to rule out depression and other psychiatric disorders. Participants refrained from prescription medications and vitamin-mineral supplements over the course of the study and from caffeine, alcohol, and tobacco for at least 24 h before each test period. Table 1Go presents the general characteristics of the participants.


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  		TABLE 1. Characteristics (mean ± SEM) of participants (n = 15)

 
Design

The study was a randomized, double blind, placebo-controlled, crossover design. There were two major factors: a supplementation phase with DHEA and placebo and acute treatments with APZ and placebo as well as a time factor (Fig. 1Go). Before the experiment conditions, participants underwent a maximal exercise treadmill test to determine maximal oxygen uptake (VO2Max). Subjects then began a period of DHEA (or placebo) supplementation. All participants took the supplement for a minimum of 2 wk before undergoing exercise challenge tests under conditions of APZ and placebo; each challenge test bout was separated by at least 72 h. After completing the first set of challenge tests, the subjects began a 2-wk washout period, after which they were given the other supplement; As before, after a minimum of 2 wk on the other supplement (DHEA or placebo), participants started a second round of exercise challenge tests under conditions of APZ and placebo. The supplementation phases were terminated when all testing was completed.



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  		FIG. 1. Time line and design for experimental sessions. SEES, Subjective exercise experience scale; VAS, visual analog scale.

 
Ingestion of DHEA or placebo

DHEA (100 mg/d) or placebo (lactose) was provided and coded by a local pharmacy (Pathways, Bethesda, MD). The supplements were prepared in capsules and labeled as A or B. None of the researchers was aware of the content of the capsules. Participants were instructed to take their supplements each morning and were given the pills in packets on a weekly basis.

Acute ingestion of APZ or placebo

APZ (0.5 mg) or placebo (lactose) was also provided as identical capsules and labeled as 1 or 2 by a local pharmacy (Pathways). The participants were given one capsule the day before the exercise challenge tests and asked to take it at 2300 h that night; they reported to the laboratory the following morning at 0700 h for testing. On arrival at the laboratory for testing, the participants were given another capsule (also containing either 0.5 mg APZ or placebo) and testing began 2 h after taking the second dose of APZ/placebo. For both supplements and treatments, the pharmacist kept the code until data collection was completed to maintain double-blinded status of the study.

Exercise testing

Maximal exercise test. The maximal exercise test was conducted on a motorized treadmill (Quinton Medtrack ST65, Quinton Instruments, Bothell, WA). Thirty minutes before beginning the test, a peripheral catheter was inserted in the antecubital fossa of a forearm for blood sampling; the catheter was kept patent with a heparin lock. The test began with a 5-min walk at 3.0 mph and 2% grade after which the speed was increased to between 5.0 and 8 mph, depending on the participants’ heart rate at the end of the warm-up; the grade was set to 0% incline. The grade was then increased by 2.5% increments every 3 min; exercise continued until volitional exhaustion (23). Oxygen uptake and CO2 production during all exercise tests was determined by the K4b2 (CosMed, Rome, Italy).

Challenge exercise test. This test entailed a 20-min treadmill exercise protocol in which subjects underwent a 5-min warm-up at 50%, followed by 10 min at 70%, and then 5 min at 90% of their previously determined VO2Max. The 90% exercise was followed by a 5-min cool-down (3 mph, 2% grade) and then walking at 3.5 mph at a 2.5% grade for 5 min. Metabolic data, heart rate, blood samples, and participant responses to subjective exercise experience scales and 100-mm visual analog scale were obtained before, during, and after exercise.

Biochemical assays

Hematocrit and hemoglobin were measured in blood samples collected before exercise and after exercise to adjust for changes in plasma volume. Samples were maintained on a rocker and analyzed within 15 min (System 9000 cell counter; Baker, Phillipsburg, NJ). Plasma lactate and glucose were used to document exercise intensity and metabolic status: lactate and glucose were collected in prechilled, sodium fluoride tubes, centrifuged, and measured within 24 h by a lactate/glucose analyzer (YSI, Yellow Springs, OH). Blood for hormones was collected in EDTA, immediately placed on ice, and centrifuged within 30 min for separation of plasma from the red cells. Hormones were measured by standard RIA procedures: cortisol, GH, DHEAS (Diagnostic Systems Laboratories, Inc., Webster, TX), DHEA (ICN Biomedicals, Inc., Costa Mesa, CA), and ACTH (Nichols Institute, San Juan Capistrano, CA). Plasma AVP was extracted and assayed by RIA as previously described by Rittmaster et al. (24). The recovery using this procedure was greater than 90%. GH levels were measured by specific RIA techniques by Covance Laboratories (Vienna, VA). All plasma was stored at –70 C and assayed in batch to minimize interassay variability. Detection limits for cortisol, ACTH, DHEAS, DHEA, and GH were 8.3 nmol/liter, 0.22 pmol/liter, 10.3 nmol/liter, 0.031 nmol/liter, and 0.2 µg/liter, respectively. Intraassay coefficients of variation (CVs) were less than 6, and 8%, and interassay CVs were less than 10 and 15% for cortisol and ACTH, respectively; intraassay CVs for DHEAS, DHEA, and GH were 8.5, 1.6, and 3.3%,and interassay CVs were 7.6, 8.4, and 5.1%, respectively. Intra- and interassay CVs for AVP were 7.5 and 12%, respectively.

Statistical analysis

The data were analyzed as a multivariate analysis of variance to control for type I errors. If overall significance was achieved, general linear models repeated-measures ANOVA with subjects as a random effect and within-subject factors of supplement and treatment and the interaction of supplement and treatment was used. Specifically, for the biochemical measures, baseline values, areas under the time curves (calculated by the trapezoidal method), and peak changes (peak to baseline) were used to reduce hormonal data to single points. The statistical package SAS (SAS Institute, Cary, NC) was used for all analyses. Standard procedures were used to calculated means and SEs of the mean.


   Results
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 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Effects of DHEA supplementation

Supplementation with DHEA had several effects on baseline and exercise-induced responses. As expected, supplementation with DHEA resulted in significant increases in plasma levels of both DHEA and DHEAS. Basal values for DHEA were 15.7 ± 0.8 and 24.6 ± 1.7 nmol/liter under placebo and DHEA conditions, respectively, and plasma DHEAS were 4.7 ± 0.4 and 12.5 ± 1.2 mmol/liter under placebo and DHEA conditions, respectively. In contrast, DHEA had no effect on plasma testosterone (placebo: 19.6 ± 1.0; DHEA: 19.4 ± 1.2 nmol/liter).

Interestingly, administration of DHEA significantly increased the AVP response to exercise. Peak AVP responses (Table 2Go) and patterns of AVP (Fig. 2Go) in response to exercise after treatment with DHEA were significantly higher than under placebo conditions. Similar trends were noted for ACTH and cortisol because peak ACTH and cortisol concentrations were consistently higher with DHEA supplementation, but the marked variability precluded significance. Table 2Go presents peak levels of ACTH, AVP, cortisol, DHEA, and GH across all treatment conditions.


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  		TABLE 2. Mean (± SEM) peak exercise-induced concentrations of plasma ACTH, AVP, cortisol, DHEA, and GH across all treatment conditions

 


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  		FIG. 2. Patterns of change in plasma AVP concentrations before, during, and after exercise across all treatment conditions: placebo/placebo (solid line and closed squares); placebo/APZ (dashed line and closed squares); DHEA/placebo (solid line and closed circles); and DHEA/APZ (dashed line and closed circles). *, Significantly different from other placebo (P ≤ 0.05).

 
Effects of APZ administration

Significant effects of APZ were noted with respect to both basal and exercise-induced responses. First, APZ induced significant increases in basal plasma GH concentrations: basal plasma GH values were 0.53 ± 0.7 and 0.97 ± 0.2 µg/liter under placebo and APZ treatments, respectively. With respect to exercise, in contrast to DHEA, which significantly increased peak exercise AVP, administration of APZ significantly blunted exercise-induced increases in AVP. Figure 1Go present the time course for exercise-induced changes in AVP under all treatment conditions. In addition to its effects on AVP, administration of AZP significantly reduced the overall exercise responses of plasma cortisol, ACTH (Fig. 3Go), and DHEA (Fig. 4Go).



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  		FIG. 3. Patterns of change in plasma cortisol and ACTH concentrations before, during, and after exercise for placebo (solid line and closed squares) and APZ (solid line and closed circles); treatments and integrated cortisol and ACTH or AUCs for placebo and APZ treatments. *, Significantly different from other time points (P ≤ 0.05). **, AUC significantly different from other treatment conditions (P ≤ 0.05).

 


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  		FIG. 4. Patterns of change in plasma DHEA concentrations before, during, and after exercise for placebo (solid line and closed squares) and APZ (solid line and closed circles); treatments and integrated DHEA or AUCs for placebo and APZ treatments.*, Significantly different from other time points (P ≤ 0.05). **, AUC significantly different from other treatment conditions (P ≤ 0.05).

 
DHEA and APZ interactions

Two significant interactions were noted. First, the combination of DHEA and APZ resulted in significant increases in the GH response to exercise. The interaction is presented in Fig. 5Go in which the time course and areas under the curve (AUCs) for GH under all conditions are presented. In addition, the glucose response to exercise was markedly affected when DHEA and APZ were taken in combination. Although DHEA alone enhanced the glucose response to exercise, the combination of DHEA and APZ attenuated the response such that the AUC for plasma glucose was significantly lower under this, compared with other conditions (Fig. 6Go).



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  		FIG. 5. Patterns of change in plasma GH concentrations before, during, and after exercise across all treatment conditions: placebo/placebo (solid line and closed squares); placebo/APZ (dashed line and closed squares); DHEA/placebo (solid line and closed circles); DHEA/APZ (dashed line and closed circles), and integrated GH or AUCs across all conditions. *, Significantly different from other time points (P ≤ 0.05). **, AUC significantly different from other treatment conditions (P ≤ 0.05).

 


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  		FIG. 6. Patterns of change in plasma glucose concentrations before, during, and after exercise across all treatment conditions: placebo/placebo (solid line and closed squares); placebo/APZ (dashed line and closed squares); DHEA/placebo (solid line and closed circles); DHEA/APZ (dashed line and closed circles), and integrated glucose or AUCs across all conditions. **, AUC significantly different from other treatment conditions (P ≤ 0.05).

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The activity of the HPA axis is regulated primarily by parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) that express CRH, AVP, or both CRH and AVP (8, 24). These neurons in turn are regulated by other neuronal projections, which coordinate and integrate excitatory and inhibitory signals (8). GABAergic neuronal activity is one mechanism regulating the HPA axis: enhanced GABAergic activity restrains the HPA axis (8). The present study was conducted to further examine the role of GABAergic activity on HPA axis functioning under both basal and stress conditions using two purported GABAergic modulators: DHEA, a GABA antagonist (1), and APZ, a GABA agonist (1, 8). Exercise was used as the stress paradigm because as a natural physiologic stressor, we have shown that it can be used to quantitatively and reproducibly activate the HPA axis (6, 7, 26, 27, 28). The results of this study suggest that acute administration of APZ restrains stress-induced HPA axis activation, as indicated by decreased exercise-induced secretion of ACTH, AVP, cortisol, and DHEA, whereas chronic use of DHEA increases exercise-induced release of AVP. Moreover, when APZ is administered acutely in combination with DHEA, exercise-induced release of GH is significantly enhanced.

Demirgoren et al. (29) have reported that DHEAS acts as a negative noncompetitive modulator of the GABAA receptor and, as such, may serve an important role in regulating neuronal excitability. The nonsignificant increases in exercise-induced ACTH and cortisol under DHEA, compared with placebo conditions, in the present study would suggest that the GABA antagonist activity of DHEA might be minimal. Alternatively, the lack of significance may indicate that withdrawal or antagonism of GABAergic tonic inhibitory activity serves a minor role in stress-induced HPA axis activity. Another possibility is that the response is gender specific because Kudilelka et al. (2) demonstrated the DHEA treatment for 2 wk significantly enhanced the ACTH response of women, but not men, to psychological stress.

In contrast to its relative lack of effect on ACTH and cortisol, DHEA significantly increased plasma AVP responses to exercise. Although this could be attributed to DHEA-induced withdrawal of GABA inhibitory actions on AVP secretion, it is also possible that DHEA-induced increases in AVP reflect enhanced NMDA excitatory activity. A number of investigators have shown in animals and animal preparations that DHEA affects NMDA receptors (30, 31, 32, 33, 34). For example, Wen et al. (30) reported that administration of DHEA to rats for 5 d significantly increased the number of NMDA binding sites in hippocampal areas. Yamaguchi and Watanabe (32) showed that plasma AVP rapidly increased when NMDA was applied to the median or medial preoptic nucleus and the PVN of rats and that prior administration of a selective NMDA antagonist significantly blocked the NMDA-induced rise in AVP. Furthermore, Orlowska-Majdak et al. (34) presented evidence that application of NMDA significantly increased AVP release from rabbit hippocampus. Thus, at least in animals, NMDA receptors are clearly important for AVP release. Finally, exercise may activate NMDA receptors in rodents. Kitamura et al. (35) found that hippocampal neurogenesis was enhanced in wild-type mice that ran for 3 wk but was unchanged in running mice that lacked the NMDA receptor epsilon-1 subunit. Further work in humans will be required to document that DHEA-NMDA-exercise interactions explain exercise-related augmentation of AVP release in association with DHEA treatment.

The effects of APZ on HPA axis activity have been studied by a number of investigators. Most studies have infused APZ and either quantified changes in ACTH and cortisol over time or have challenged the axis by injections of CRH, AVP, or ACTH. No one has examined responses to a physiologic challenge such as exercise. We found an attenuation of exercise-induced ACTH and cortisol, which is consistent with studies showing APZ attenuation of ACTH and cortisol induced by stress, naloxone, hexarelin, insulin-induced hypoglycemia, and AVP (15, 16, 17, 18, 19, 20, 21, 22). The only studies without attenuation of ACTH used CRH (36, 37). Based on their findings that the cortisol response to exogenous ACTH was blunted by APZ, Grottoli et al. (17, 18) postulated that APZ might directly inhibit the adrenal gland. In summary, the inhibitory action of APZ on ACTH and cortisol could be through CRH and/or AVP or through direct actions on the adrenals, but the precise mechanism cannot be conclusively determined from the available data.

In addition to blunting of cortisol and ACTH, we found that APZ attenuated the AVP and DHEA responses to exercise. The finding that acute administration of APZ significantly blunted stress-induced release of AVP is consistent with the literature, despite differences in the approaches (11). Chiodera et al. (11) demonstrated involvement of a GABAergic mechanism in regulating the AVP response to physical exercise in men when they showed that the GABA agonist, sodium valproate, completely abolished exercise-induced increases in plasma AVP. Moreover, Otake et al. (14) reported a time- and dose-dependent decrease in hypertonic saline-induced increases in plasma AVP of conscious rats in response to intracerebroventricular administration of GABA.

The effects of APZ on the DHEA response to exercise had not been previously reported. Grottoli et al. (17) reported that DHEA, as well as ACTH and cortisol, was significantly blunted when humans were given APZ in combination with canrenoate, a mineralocorticoid receptor antagonist that enhances both spontaneous and CRH-stimulated release of ACTH and cortisol. When Grottoli et al. (18) administered exogenous ACTH after pretreatment with APZ, DHEA was not reduced, despite a significant decrease in the cortisol response. However, the authors did note that APZ pretreatment significantly decreased basal plasma DHEA (18), which is in contrast to Kroboth et al. (38), who reported that administration of APZ significantly enhanced basal levels of DHEA but not DHEAS. In the present study, APZ had no observable effect on basal DHEA or DHEAS, but it did blunt exercise-induced responses. Thus, variable DHEA responses to APZ are noted in the literature. Reasons for the contradictory results are not clear but may reflect the dose of APZ, the specificity of the stimulus, and/or the timing of the blood sampling.

Lastly, whereas APZ blunted HPA axis activity, we found that it enhanced basal secretion of GH. This increase in the tonic release of GH has been shown by a number of investigators (15, 18, 20, 25) and is believed to reflect the stimulatory role of GABAA activity on GH. As early as 1980 Cavagnini et al. (10) showed that administering 5 g GABA orally to men caused a significant elevation in basal plasma GH. Despite our finding of increased basal levels, we saw no effect of APZ on exercise stress-induced increases in GH, which is in contrast to the findings of others (12, 16). Coiro et al. (12) reported that administration of sodium valproate, another GABAergic agonist, abolished the GH response to exercise in men. Others have also shown that APZ blunts the GH response when pharmacologic methods are used to stimulate GH secretion (15, 16). Giordano et al. (16) found an attenuation of GH in response to insulin-induced hypoglycemia, and Arvat et al. (15) observed a significant reduction in the GH response to hexarelin, a synthetic GH-releasing peptide that stimulates GH release, when APZ was provided before the provocations. It is intriguing to note that when Cavagnini et al. (10) administered 18 g GABA to men daily for 4 d, the GH response to insulin-induced hypoglycemia was significantly blunted, compared with placebo. Although further work will be required to unravel GABAergic effects on basal and stimulated GH release, differences noted in the literature may reflect the nature of the stimulus and/or the effects of APZ on other neural pathways that regulate GH release.

Unexpectedly we found that the combination of DHEA and APZ enhanced exercise-induced release of GH. Although the mechanism for this enhanced response is uncertain, it is likely to reflect interactions and/or crosstalk between GABAA and NMDA receptor activation and/or density. Pinilla et al. (25) have shown that the stimulatory effect of GABA on GH release in neonatal rats was abolished by pretreatment with an NMDA receptor antagonist and that GH release was enhanced after treatment with NMDA. This information coupled with the postulated effect of DHEA on NMDA receptors and glutamate release may possibly account for the DHEA and APZ interaction.

Finally, administration of APZ in combination with DHEA blocked the exercise-induced increase in plasma glucose. This observation is both new and unexpected. Because the same combination increased the GH response to exercise, one would anticipate the opposite effect, i.e. an increase in plasma glucose. Additional work will be required to identify this apparent anomalous finding.

In summary, the results of this study suggest that enhanced GABAA activity inhibits exercise-induced increases in ACTH, cortisol, AVP, and DHEA but that the specific sites in which GABA acts might be diverse. The sites to consider would be magnocellular and parvocellular neurons of the supraoptic nucleus and PVN, respectively, and perhaps even the adrenal cortex. In contrast, enhancement of GABAA activity promotes the tonic release of GH. That administration of DHEA increases plasma AVP, in the presence and absence of APZ, which significantly blunts AVP, suggests that DHEA alters a subset of receptors, possibly NMDA receptors, involved in AVP release.


   Footnotes
 
The opinions and assertions expressed herein are those of the authors and should not be construed as reflecting those of the Uniformed Services University of the Health Sciences (USUHS) or the Department of Defense.

This work was supported by USUHS Research Project RO9142.

First Published Online May 31, 2005

Abbreviations: APZ, Alprazolam; AUC, area under the curve; AVP, arginine vasopressin; CV, coefficient of variation; DHEA, dehydroepiandrosterone; DHEAS, DHEA sulfate; GABAA, {gamma}-amino-butyric acid A; HPA, hypothalamic-pituitary-adrenal; NMDA, N-methyl-D-aspartate; PVN, paraventricular nucleus; VO2Max, maximal oxygen uptake.

Received December 21, 2004.

Accepted May 20, 2005.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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