Perinatal glucocorticoid (GC) treatment accelerates lung maturation but may compromise health in adulthood, possibly via changes in hypothalamo-pituitary adrenal (HPA) activity. This study used western blot analysis and a well established in vitro method to investigate the effects of perinatal GC treatment on the expression and function of annexin 1 (ANXA1), a 37kDa protein which mediates facets of GC action in the neuroendocrine and host defence systems. Male rats were treated with dexamethasone (dex) (a) i.p. 1microgram per 10microlitres per gramme b.wt. on post-natal days (P) 3, 5 & 7, (b) post-natally via the milk from mothers given dex in the drinking water (1microgram per ml) from P1-7 and (c) pre-natally from mothers given dex in the drinking water (1microgram per ml) from days 18-21 of gestation. Blood and tissue were collected at P60 for hormone assay, functional studies and western blot analysis. ANXA1 protein was found mainly intracellularly in all tissues studied but small amounts were also detected on the cell surface. All of the perinatal dex treatments caused a marked decrease (vs. controls) in both cell surface and intracellular ANXA1 in the anterior pituitary (AP) and adrenal glands and in cell surface but not intracellular ANXA1 in lung macrophages. Post-natal dex treatment did not affect ANXA1 expression in the hypothalamus but increased cell surface ANXA1 in the hippocampus, whereas pre-natal dex treatment reduced ANXA1 expression in the hypothalamus and the hippocampus. Pre-natal dex treatment also (a) increased basal ACTH release in vitro and reduced the ANXA1-dependent ability of dex to inhibit forskolin-evoked ACTH release (P<0.05) and (b) decreased the basal plasma corticosterone level (p<0.05). The data accord with reports that perinatal dex treatment alters basal and stimulated HPA function in the adult rat and provide new evidence that pre- and post-natal dex treatments induce differing tissue-specific changes in the expression and cellular disposition of the GC-regulated protein, ANXA1, in the adult.
03 - 04 Dec 2001
Society for Endocrinology