Effects of dehydroepiandrosterone and alprazolam on hypothalamic-pituitary responses to exercise.
BACKGROUND
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.


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


METHODS
The study setting was the general community.


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


METHODS
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.


METHODS
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.
Deuster
Patricia A
PA
MPH, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799, USA. pdeuster@usuhs.mil
Faraday
Martha M
MM
Chrousos
George P
GP
Poth
Merrily A
MA
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000525:Alprazolam / Q000008:administration & dosage*; D001127:Arginine Vasopressin / Q000097:blood; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000008:administration & dosage*; D015444:Exercise; D018757:GABA Modulators / Q000008:administration & dosage*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology
D000276:Adjuvants, Immunologic; D018757:GABA Modulators; D011963:Receptors, GABA-A; D001127:Arginine Vasopressin; D003687:Dehydroepiandrosterone; D000525:Alprazolam