GR gene haplotypes and hypothalamus-pituitary-adrenal (HPA) axis responses to stress

The hypothalamus–pituitary–adrenal (HPA) axis is vital for an organism’s response to physical or psychosocial stimulation. Chronic dysregulation of HPA axis activity is related to several psychiatric and psychosomatic disorders. Cortisol, the end product of this endocrine system, affects a multitude of systems in the body, including the HPA axis itself and it also has an impact on behavior. The effects of cortisol are primarily mediated by the glucocorticoid receptor (GR). A number of findings document the functional relevance of several GR gene polymorphisms with regard to HPA axis regulation and we recently demonstrated an association between common GR gene polymorphisms and cortisol responses to a psychosocial stressor. In order to further characterize the effects of genetic variation of the GR on HPA axis regulation, 600 subjects were screened for common GR gene haplotypes. Subsequently, 220 subjects were extensively phenotyped. Basal HPA axis function, cortisol and ACTH responses to psychosocial and pharmacological stimulation, several indices of GC sensitivity of different target tissues as well as memory performance were assessed. Results will be presented at the conference.