Journal of Clinical and Diagnostic Research. 2023 Feb, Vol-17(2): CC01-CC04 1 1 DOI: 10.7860/JCDR/2023/61231.17535 Original Article Physiology Section Dehydroepiandrosterone and Acute Stress Attenuation: An Interventional Rodent Study INTRODUCTION The maintenance of internal balance (homeostasis) at times of real or perceived stress is made possible by the evolution of stress response that brings about adaptive changes through the activation of autoregulated neural and hormonal systems. Of the two mechanisms, the hormonal mechanism serves as the key regulator in mediating the Hypothalamic-Pituitary-Adrenal (HPA) axis. By the activation of HPA axis glucocorticoid is ultimately released from adrenal cortex and mediates the adaptive response to stress [1]. Glucocorticoids are primarily concerned with ensuring energy availability by mobilisation and distribution of energy to various organ systems in appropriation to demands, both at basal and stressed states thus rendering adaptive response at times of stress an efficient mechanism to meet the demands of the dire moments [2]. Glucocorticoids exert action via both non genomic and genomic mechanisms and its effects could be observed almost on all tissues in the body as its receptors are widely distributed in all body systems [3,4]. These neuroendocrine mediated metabolic, physiological and behavioural adaptations that ensures improved survival in the face of temporary stressors by establishing stability through changes, is referred as allostasis [5,6]. Such adaptations if persistent for prolonged periods or repeated can often lead to physiologic dysregulation with poor health outcomes like increased susceptibility to infections, cardiovascular disease, metabolic syndrome, obesity, cancer, and mental health disorders that constitutes the allostatic load [1]. Stress affects mental health and on the long-term impairs the quality of life. Therefore, in the recent past many research endeavours in the field of mental health have revealed various endogenous biomolecules to possess efficient stress buffering capacity. In this vein, DHEA and its sulphated derivative DHEA-Sulfate (DHEAS) which were previously considered to serve only as a precursor of potent androgen and oestrogens on peripheral conversion, were recently found to have a plethora of beneficial effects that includes stress attenuation as it has anti-glucocorticoid properties [7]. DHEA is observed to modulate endothelial function, improve insulin sensitivity, reduce inflammation, improve blood flow, regulate body composition, bone metabolism, sexual function, enhance neuroprotection, improve cognition and memory as well counteract the immunosuppressive actions of corticosteroid [8,9]. Age related metabolic derangement, cognitive decline, neurodegenerative disorders as well as the aetiopathology of many psychiatric illness lie with derangement in endogenous DHEA levels [10-12]. DHEA, as an anti-stress agent, is observed to prevent the stress induced inhibition in body weight gain, increase in adrenal weight, and concentration of glucocorticoid receptor levels in liver, thymus, and spleen when administered to stress male Sprague-Dawley rats and it also reduces the lipid peroxidation levels in the liver and heart [13]. Similarly, DHEA is also observed to inhibit the stress induced corticosterone mediated inhibition of testosterone in experimentally stressed adult Sprague-Dawley rats [14]. Previous research reported a contradictory observation where the administration of sulphated TAMILSELVAN KUPPUSAMY 1 , GAYATHRI VEERARAGHAVAN 2 , SANTHI SILAMBANAN 3 , MURALISWARAN PERUMAL 4 , PADMAVATHI RAMASWAMY 5 Keywords: Adrenal androgen, Anxiety, Immobilisation, Psychological stress, Serum corticosterone ABSTRACT Introduction: Stress activates hypothalamo-pituitary-adrenal axis leading to the release of glucocorticoid that mediates the stress response. This adaptive response is self-limited but if persistent for prolonged periods can lead to disease states. Nature has endowed the body with efficient buffer systems to attenuate the stress effects and Dehydroepiandrosterone (DHEA), a steroid hormone with neuromodulatory functions is implicated as an efficient candidate to buffer stress. Aim: To assess the effect of prophylactic administration of DHEA in the attenuation of acute stress in male Wistar rats. Materials and Methods: This interventional study was carried out at centre for Toxicology and Developmental Research, Sri Ramachandra Institute of Higher Education and Research, Chennai, between June 2021 and August 2021, in compliance with the animal welfare guidelines of CPCSEA, and in accordance to the protocol approved by Institutional animal ethics committee. The 18 male Wistar rats approved for the study were segregated into 3 groups with 6 animals in control (no stress) group, 6 in stress group and 6 in intervention group that received DHEA prophylactically 30 min before stress procedure. Animals in stress and intervention groups were subjected to one hour immobilisation stress. Blood samples were collected from all animals after the stress period and serum corticosterone, the stress marker, was estimated. The data were expressed as mean±standard error of mean (mean±SEM) and Mann-Whitney U test was used to test the significant difference between the: (i) control & stress groups; (ii) stress & study groups; and (iii) control & study groups. The p-value<0.05 was considered significant. The analysis was done using SPSS version 23.0. Results: The values of corticosterone in control, stress and intervention groups were 26.6±4.4 ng/mL, 51.6±3.9 ng/mL and 23.4±3.6 ng/mL, respectively. Significant difference in the mean serum corticosterone levels with p-value 0.013 between control and stress groups and with p-value 0.008 between stress and DHEA groups were observed. Conclusion: It could be observed from the findings that prophylactic DHEA administration attenuated acute stress efficiently in male Wistar rats as reflected by the significant decrease in serum corticosterone levels in the group that received DHEA intervention, thus inferring the efficiency of DHEA in stress buffering.