Human NR3C2 peptide

Thyroid hormones play key roles in cellular growth, development and metabolism. Although there is a strong genetic influence on thyroid hormone levels, the genes involved are widely unknown. The levels of circulating thyroid hormones are tightly regulated by thyrotropin (TSH), which also represents the most important diagnostic marker for thyroid function. Therefore, in order to identify genetic loci associated with TSH levels, we performed a discovery meta-analysis of two genome-wide association studies including two cohorts from Germany, KORA (n 1287) and SHIP (n 2449), resulting in a total sample size of 3736. Four genetic loci at 5q13.3, 1p36, 16q23 and 4q31 were associated with serum TSH levels. The lead single-nucleotide polymorphisms of these four loci were located within PDE8B encoding phosphodiesterase 8B, upstream of CAPZB that encodes the -subunit of the barbed-end F-actin-binding protein, in a former ogene desert' that was recently demonstrated to encode a functional gene (LOC440389) associated with thyroid volume, and upstream of NR3C2 encoding the mineralocorticoid receptor. The latter association for the first time suggests the modulation of thyroid function by mineral corticoids. All four loci were replicated in three additional cohorts: the HUNT study from Norway (n 1487) and the two German studies CARLA (CARLA, n 1357) and SHIP-TREND (n 883). Together, these four quantitative trait loci accounted for approximate to 3.3 of the variance in TSH serum levels. These results contribute to our understanding of genetic factors and physiological mechanisms mediating thyroid function.

Objective: Adolescence is a time of increased susceptibility to environmental stress and mood disorders, and girls are particularly at risk. Genes interacting with the environment (G x E) are implicated in hypothalamic-pituitary-adrenal axis dysregulation, hippocampal volume changes and risk or resilience to mood disorders. In this study, we assessed the effects of stress system G x E interactions on hippocampal volumes and cortisol secretion in adolescent girls. Methods: We recruited 229 girls aged 12-18 years, and scans were obtained from 202 girls. Of these, 76 had been exposed to higher emotional trauma (abuse or neglect). Hippocampal volumes were measured using Freesurfer and high-resolution structural magnetic resonance imaging scans. Saliva samples were collected for measurement of cortisol levels and genotyping of stress system genes: FKBP5, NR3C1 (both N = 194) and NR3C2 (N = 193). Results: Among girls with the 'G' allelic variant of the NR3C1 gene, those who had been exposed to higher emotional trauma had significantly smaller left hippocampal volumes (N = 44; mean = 4069.58 mm(3), standard deviation = 376.99) than girls who had been exposed to minimal emotional trauma with the same allelic variant (N = 69; mean = 4222.34 mm(3), standard deviation = 366.74). Conclusion: In healthy adolescents, interactions between emotional trauma and the 'protective' NR3C1 'GG' variant seem to induce reductions in left hippocampal volumes. These G x E interactions suggest that vulnerability to mood disorders is perhaps driven by reduced 'protection' that may be specific to emotional trauma. This novel but preliminary evidence has implications for targeted prevention of mood disorders and prospective multimodal neuroimaging and longitudinal studies are now needed to investigate this possibility.