Glucocorticoid "programming" and PTSD risk.
Epidemiological data have linked an adverse fetal environment with increased risks of cardiovascular, metabolic, neuroendocrine, and psychiatric disorders in adulthood. Prenatal stress and/or glucocorticoid excess might underlie this link. In animal models, prenatal stress, glucocorticoid exposure or inhibition/knockout of 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD-2), the feto-placental barrier to maternal glucocorticoids, reduces birth weight and causes permanent hypertension, hyperglycemia, increased hypothalamic-pituitary-adrenal (HPA) axis activity and behavior resembling of anxiety. In humans, 11 beta-HSD-2 gene mutations cause low birth weight and placental 11 beta-HSD-2 activity correlates directly with birth weight and inversely with infant blood pressure. Low birth weight babies have higher plasma cortisol levels throughout adult life, indicating HPA programming. In human pregnancy, severe maternal stress affects the offspring HPA axis and associates with neuropsychiatric disorders. Posttraumatic stress disorder (PTSD) appears to be a variable in the effects. Intriguingly, some of these effects appear to be 'inherited' into a further generation, itself unexposed to exogenous glucocorticoids at any point in the lifespan from fertilization, implying epigenetic marks persist into subsequent generation(s). Overall, the data suggest that prenatal exposure to excess glucocorticoids programs peripheral and CNS functions in adult life, predisposing to some pathologies, perhaps protecting from others, and these may be transmitted perhaps to one or two subsequent generations.
Seckl
Jonathan R
JR
Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. J.Seckl@ed.ac.uk
Meaney
Michael J
MJ
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000502:physiology; D000818:Animals; D001724:Birth Weight; D001921:Brain / Q000254:growth & development / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012306:Risk; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology*
D005938:Glucocorticoids; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2