Ceyda N. Ilhan1, Robin Lengton1, Carlijn A. Hoekx2,3, Lisa B.D. Brinkman2, Patrick C.N. Rensen2,3, Elisabeth F.C. van Rossum1, Johanneke E. Oosterman1, Mariëtte R. Boon1
1 Obesity Center CGG, Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;
2 Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands;
3 Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
South Asians (SA) have an increased risk of developing cardiometabolic diseases compared with Europids (EUR), despite having lower plasma cortisol levels. This may be the result of increased glucocorticoid receptor (GR) sensitivity, which we aimed to study by comparing glucocorticoid regulation between SA and EUR.
Anthropometric measures, perceived stress score-14 (PSS-14), corticosteroid-binding globulin (CBG), and glucocorticoids (in plasma and hair) were determined in healthy lean SA and EUR women (n=12/group). In a subset of the population (n=9/group), GR sensitivity was determined based on the dexamethasone-induced up- and downregulation of glucocorticoid target genes and monocyte markers, as well as the relative expression of GR isoforms (GR-α, GR-β, GR-P) in peripheral blood mononuclear cells (PBMCs).
SA had significantly higher fat percentage than EUR (31.5%±5.9 vs. 24.1%±6.5) despite comparable body mass index, and tended to have a higher waist-to-height ratio, suggesting central adiposity. SA also tended to have a higher PSS-14 score, but significantly lower plasma cortisol levels than EUR (447.8 µmol/l [324.0–543.5] vs. 638.4 µmol/l [549.9–715.8]), which was not explained by differences in CBG levels, or reflected in long-term glucocorticoids in hair. There were no significant differences in the dexamethasone-mediated change in glucocorticoid-target gene expression between ethnicities. Interestingly, SA had significantly higher GR-P expression (0.215 [0.186–0.235] vs. 0.175 [0.163–0.181]), and a stronger dexamethasone-induced downregulation and weaker upregulation of several monocyte markers. Overall, our data show evidence for ethnic differences between SA and EUR in glucocorticoid regulation and response. Future research will focus on inclusion of male participants.