Glucocorticoid Receptors and the Role of Glucocorticoids in Fetal Lung Development

Abstract

The cellular mechanism of glucocorticoid effects upon fetal lung was examined in studies of specific binding activity for corticosteroids. Cytoplasm of fetal rabbit lung contains receptor sites for [(3)H]dexamethasone at a concentration of 0.43 +/- 0.04 pmol/mg of cytosol protein, and the apparent dissociation constant for the binding reaction is 2.7 +/- 0.4 nM. The ability of various steroids to compete with labeled dexamethasone for binding to receptor correlates with their biologic potency. The hormone-receptor complex formed in vitro at 0 degrees binds with high affinity at 20 degrees to isolated lung nuclei. It is estimated that there are 9500 nuclear binding sites and 12,000 cytoplasmic receptor sites per fetal lung cell. During the last 12 days of gestation in a rabbit, the concentration of cytoplasmic receptor in lung is constant and is 2- to 5-times greater than receptor-site concentration in fetal skin, kidney, heart, muscle, gut, liver, brain, thymus, and placenta. These findings demonstrate that the early steps in the mechanism of glucocorticoid action in target tissues are present in lung cells, and suggest that these hormones accelerate fetal lung differentiation and surfactant production in animals by the induction of new protein synthesis mediated by receptor.