The expression of serum steroid sex hormones and steroidogenic enzymes following intraperitoneal administration of dehydroepiandrosterone (DHEA) in male rats

Abstract

The adrenals of humans and primates could secrete large amounts of dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA-S) in the circulation, which act as precursors of active steroid hormones in a long series of peripheral target intracrine tissues. The marked decline of serum DHEA and DHEA-S concentrations with age in humans has been incriminated in the development of various pathologies. Therefore, this study aims to provide detailed information on the effects of the intraperitoneal injection of DHEA on circulating steroid hormones and their metabolites and their trade-off relationship over 24 h in male rats. In this study, 100 healthy adult male Sprague-Dawley (SD) rats were randomly divided into three groups: control, 25 mg kg(-1) DHEA-treated and 100 mg kg(-1) DHEA-treated. The animals were sacrificed at 0, 1.5, 3, 6, 12 or 24 h, and the samples were collected for subsequent analysis. Total cholesterol (TC) markedly decreased 3h after the administration of 100 mg kg(-1) DHEA, but markedly increased 12h after administration. The DHEA-S, progesterone (P), testosterone (T), oestradiol (E(2)), cortisol (Cor) and aldosterone (Ald) concentrations also markedly increased after DHEA administration, with serum DHEA-S, T, E(2) and Cor levels peaking at 1.5 h. Over time, steroid hormone levels were depressed, but serum Cor and Ald levels were markedly elevated relative to the control group at 24 h. Furthermore, DHEA treatment produced a significant increase in P450scc, 17beta-HSDIII, CYP17alpha and 3beta-HSD mRNA expression at 1.5 h, but a decided decrease in P450scc and StAR mRNA expression at 12 and 24 h, and CYP17alpha and 17beta-HSDIII expression at 12 h in the 100 mg kg(-1) DHEA group. In total, the results of the present study indicate that DHEA at high pharmacological doses may affect steroid through an effect on steroidogenic enzymes.