Endocrine Abstracts

There is convincing evidence in animals suggesting a role for prenatal glucocorticoid overexposure in the programming of adult metabolic diseases. Evidence for glucocorticoid-mediated fetal programming in humans often comes from observational studies in preterm babies with variable disease courses, in whom it is difficult to distuinguish programming from other effects.

Preterm infants early in their neonatal course are subject to stressful and sometimes even critical events, including respiratory distress, intubation and mechanical ventilation, septicaemia, necrotizing enterocolitis, and insertion of venous lines. Obviously, during this period their chances for survival are strongly dependent on the effects of antenatal and/or postnatal glucocorticoid treatment.

However, recent studies have shown that once the neonatal threats are resolved, preterm survivors continue to show effects of increased glucocorticoid bioactivity, such as abdominal fat accumulation, glucose intolerance, and raised blood pressure. Several mechanisms with a central role for hypothalamus–pituitary–adrenal axis functioning may underpin these observations. First, subjects who are genetically more sensitive to the effects of endogenous or exogenous glucocorticoids may survive preterm birth easier but are predisposed later to metabolic diseases. Second, extremely stressful insults in early life may induce site-specific alterations in the epigenetic code of the glucocorticoid receptor gene promotor, leading to decreased central feedback suppression, and thus, enhanced stress responsivenss and disease. Third, exposure to glucorticoids may impact on the development of several organs, depending on the glucocorticoid receptor genotype.