Endocrine Abstracts

It is well documented that inappropriate exposure to glucocorticoids (GCs) in early life stunts growth and predisposes the individual to metabolic disorders, including type 2 diabetes. Evidence suggests that these programming actions involve alterations in GC receptor expression. However, the precise mechanisms remain to be determined. As GCs are known to modify both the neuroendocrine control of growth hormone (GH) secretion and the peripheral effects of GH on growth and metabolism, we hypothesize that the deleterious consequences of GC programming may involve permanent alterations in the GC-sensitive facets of the GH axis. In order to test this hypothesis, Sprague-Dawley rats were treated with dexamethasone (DEX) neonatally (1mg/kg body weight on postnatal days 3, 5 and 7, controls received saline) or prenatally via the mother's drinking water (1mg/l on gestational days 18-21). The growth rate of the DEX treated animals was stunted during the period of treatment and there was no catch up growth. Although neither DEX treatment influenced adipocyte size, the pre- but not postnatal treatment produced a marked decrease in the levels of the GC-inducible protein annexin-1 in adipose tissue (p<0.01). In contrast, annexin-1 levels in the liver, another GC sensitive tissue, were increased by pre- but not postnatal DEX (p<0.05), while hepatic GH receptor mRNA expression was unchanged. Early life GC treatment also caused a marked decrease in annexin-1 expression in the pituitary (p<0.05) but failed to alter pituitary GH content, although interestingly prolactin content was markedly decreased (p<0.01). These results suggest that there is a critical window during which early life DEX produces tissue specific changes in GC-regulated genes that are concerned with the regulation of the GH axis.

We are grateful to the Society for Endocrinology for financial support.