CONTEXT: Metabolic syndrome (MetS) shares several similarities with hypercortisolism. OBJECTIVES: To evaluate hypothalamic-pituitary-adrenal (HPA) axis sensitivity to dexamethasone (DEX), NR3C1 single nucleotide polymorphisms (SNPs), and expression of glucocorticoid receptor (GR) isoforms and cytokines in peripheral immune cells of MetS patients and controls. DESIGN: Prospective study with 40 MetS patients and 40 controls was conducted at the Ribeirão Preto Medical School University Hospital. METHODS: Plasma and salivary cortisol were measured in basal conditions and after 0.25, 0.5, and 1 mg of DEX given at 2300 h. In addition, p.N363S (rs6195), p.ER22/23EK (rs6189-6190), and BclI (rs41423247) SNPs were evaluated by quantitative polymerase chain reaction allelic discrimination. Exons 3 to 9 and exon/intron boundaries of NR3C1 were sequenced. GR isoforms and cytokines (IL1B, IL2, IL4, IL6, IL8, IL10, IFNγ, TNFα) expression were assessed by quantitative polymerase chain reaction. RESULTS: Plasma and salivary cortisol (nmol/L) after 1-mg DEX were higher in MetS patients compared with controls (PF: 70.2 ± 17.3 vs 37.9 ± 2.6, P = .02, and SF: 4.9 ± 1.7 vs 2.2 ± 0.3, P < .0001). After all DEX doses, a lower number of MetS patients suppressed plasma and salivary cortisol compared with controls. The BclI genotypic frequencies (%) differed between patients (CC:56/CG:44) and controls (CC:50/CG:32.5/GG:17.5) (P = .03). The GRβ was overexpressed (fold = 100.0; P = .002) and IL4 (fold = -265.0; P < .0001) was underexpressed in MetS. CONCLUSION: MetS patients exhibited decreased HPA sensitivity to glucocorticoid feedback. Moreover, the BclI polymorphism lower frequency, GRβ overexpression, and IL4 underexpression might underlie the molecular mechanism of glucocorticoid resistance in MetS. Thus, HPA axis dysregulation might contribute to MetS pathogenesis.
CONTEXT: Metabolic syndrome (MetS) shares several similarities with hypercortisolism. OBJECTIVES: To evaluate hypothalamic-pituitary-adrenal (HPA) axis sensitivity to dexamethasone (DEX), NR3C1 single nucleotide polymorphisms (SNPs), and expression of glucocorticoid receptor (GR) isoforms and cytokines in peripheral immune cells of MetS patients and controls. DESIGN: Prospective study with 40 MetS patients and 40 controls was conducted at the Ribeirão Preto Medical School University Hospital. METHODS: Plasma and salivary cortisol were measured in basal conditions and after 0.25, 0.5, and 1 mg of DEX given at 2300 h. In addition, p.N363S (rs6195), p.ER22/23EK (rs6189-6190), and BclI (rs41423247) SNPs were evaluated by quantitative polymerase chain reaction allelic discrimination. Exons 3 to 9 and exon/intron boundaries of NR3C1 were sequenced. GR isoforms and cytokines (IL1B, IL2, IL4, IL6, IL8, IL10, IFNγ, TNFα) expression were assessed by quantitative polymerase chain reaction. RESULTS: Plasma and salivary cortisol (nmol/L) after 1-mg DEX were higher in MetS patients compared with controls (PF: 70.2 ± 17.3 vs 37.9 ± 2.6, P = .02, and SF: 4.9 ± 1.7 vs 2.2 ± 0.3, P < .0001). After all DEX doses, a lower number of MetS patients suppressed plasma and salivary cortisol compared with controls. The BclI genotypic frequencies (%) differed between patients (CC:56/CG:44) and controls (CC:50/CG:32.5/GG:17.5) (P = .03). The GRβ was overexpressed (fold = 100.0; P = .002) and IL4 (fold = -265.0; P < .0001) was underexpressed in MetS. CONCLUSION: MetS patients exhibited decreased HPA sensitivity to glucocorticoid feedback. Moreover, the BclI polymorphism lower frequency, GRβ overexpression, and IL4 underexpression might underlie the molecular mechanism of glucocorticoid resistance in MetS. Thus, HPA axis dysregulation might contribute to MetS pathogenesis.
Authors: Amanda N Noroña-Zhou; Alyssa Morgan; Laura M Glynn; Curt A Sandman; Tallie Z Baram; Hal S Stern; Elysia Poggi Davis Journal: Dev Psychobiol Date: 2020-03-01 Impact factor: 3.038
Authors: Marieke J van Leijden; Brenda W J H Penninx; Charles Agyemang; Miranda Olff; Marcel C Adriaanse; Marieke B Snijder Journal: Soc Psychiatry Psychiatr Epidemiol Date: 2018-05-23 Impact factor: 4.328
Authors: Rocío D V Fernández; Ariana Díaz; Bettina Bongiovanni; Georgina Gallucci; Diego Bértola; Walter Gardeñez; Susana Lioi; Yésica Bertolin; Romina Galliano; María L Bay; Oscar Bottasso; Luciano D'Attilio Journal: Front Endocrinol (Lausanne) Date: 2020-03-20 Impact factor: 5.555
Authors: Alejandro F De Nicola; Maria Meyer; Rachida Guennoun; Michael Schumacher; Hazel Hunt; Joseph Belanoff; E Ronald de Kloet; Maria Claudia Gonzalez Deniselle Journal: Int J Mol Sci Date: 2020-03-20 Impact factor: 5.923