Effects of Acrolein on the Production of Corticosterone in Male Rats.

Abstract

Acrolein, an a, β-unsaturated aldehyde, exits in a wide range of sources. Acrolein can be not only generated from all type of smoke ( including cigarette smoke) but also produced endogenously from the process of lipid peroxidation or anticancer drug (e.g. cyclophosphamide). The influence of acrolein at many cellular sites is due to its electrophilic character via binding to and depleting cellular nucleophiles such as glutathione. It has been demonstrated that acrolein may react directly with DNA, particularly guanine residues. Although the toxicity of acrolein has been extensively studied, there is little information about its impact on hormone release. This study aimed at the effect of acrolein on hypothalamic-pituitary-adrenal (H-P-A) axis, a part of neuroendocrine system that can regulate many body processes including immune system and energy storage. In an in vitro study, zona fasciculata-reticularis (ZFR) cells (5×105 cells/ml) isolated from male rat adrenal cortex were incubated with acrolein (10−11-10−7 M) for 1 h and the results showed that corticosterone concentrations in media were decreased in a dose-dependent manner. Acrolein also desensitized ZFR cells to adrenocorticotropic hormone (ACTH). In an in vivo study, male rats were administrated with acrolein (i.p., 2 mg/ml/kg) for 1 or 3 days. Venous blood were collected from right jugular catheter at 0, 15, 30, 60, 120 min after challenging with ACTH (5 μg/ml/kg). The plasma corticosterone in response to ACTH increased slower in acrolein-pretreated rats than in control rats. Further investigating the steroidogenic pathway in ZFR cells, the protein expressions of steroidogenic acute regulatory protein (StAR) and the upper receptor-melanocortin 2 receptor (MC2R) were attenuated by the administration of acrolein. These results suggest that acrolein decreased the release of corticosterone via an inhibition on the response of ZFR cells to ACTH and the reduction of protein expressions of StAR and MC2R.