814-4 Effect of Administration of Dehydroepiandrosterone on Cyclic-Guanidine-Monophosphate Plasma Levels in Men of Advancing Age

Abstract

Epidemiologic data suggest beneficial effects of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DS) in atherosclerosis and coronary artery disease. Aging is accompanied by a progressive decline in the secretion of DHEA and DS, paralleling that of growth hormone (GH) insulin like growth factor I (IGF-I) axis. Previous studies reported a significant increase of IGF-I serum levels after replacement therapy with DHEA in advancing age men and IGF-I has been shown to have a potent vasodilator effect in the forearm arterial blood flow in humans and the rat renal afferent microvasculature; an effect that can be blocked by inhibition of endothelial derived relaxing factor (EDRF), nitric oxide (NO). We investigated the effect of administration of DHEA on plasma levels of cyclic guanidine monophosphate (cGMP), the second messenger of NO activity and an indirect assay of NO release. We included 34 nonobese men, body mass index (BMI) 22–26 kg/m. age 47–74 years, normotensive and non insulin resistant in a double blind, placebo controlled, randomized study: 18 were treated with DHEA 150 mg daily for 12 days and 16 with placebo. DHEA increased from 3.7 ± 0.2 to 15.0 ± 1.4 μ m/L (p < 0.001) in the DHEA group. No changes were observed in the placebo group. cGMP plasma levels increased from 3.22 ± 0.2 to 6.05 ± 0.21 Pmol/ml(p < 0.005) after administration of DHEA. In the placebo group no significant changes were observed. BMI, fasting insulin, serum lipids and blood pressure did not change during the study. The increase of cGMP in the DHEA treated patients presumably occurs through increased NO production. We suspect that DHEA increases NO via IGF-I stimulation and this might be one of the mechanisms of the protective action of DHEA against coronary ischemic disease.