Cytoplasmic receptor for glucocorticoids in lung of the human fetus and neonate.
Open Access
- 1 February 1974
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 53 (2), 477-486
- https://doi.org/10.1172/jci107581
Abstract
In fetal animals, glucocorticoids accelerate development of the lung and cause precocious appearance of alveolar surfactant. To determine if the human lung also can respond to corticosteroids, we examined lungs of the human fetus and neonate for both cytoplasmic binding and nuclear uptake of glucocorticoids. In slices of fetal lung incubated with [3H]dexamethasone at 2 degrees C, specific macromolecular binding occurs primarily in the "cytoplasmic" fraction. After further incubation at 37 degrees C. nearly 75% of the radioactivity localizes in the "nuclear" fraction with a concentration of 0.3 pmol/mg DNA at apparent dexamethasone saturation (47 nM). The cytoplasmic receptor binds dexamethasone in vitro with high affinity (dissociation constant = 8.9 nM), and the affinity of various other steroids correlates with their glucocorticoid potency. Receptor was present in lungs of fetuses and neonates of gestational age 12-43 wk, with a mean concentration in hysterotomy specimens of 0.24 pmol sites/mg cytosol protein. Similar binding activity was present at lower concentration in fetal liver, gut, kidney, heart, muscle, and skin. Cytoplasmic receptor was not detected in lung and liver of premature infants with respiratory distress syndrome. This deficit appears to result from increased levels of endogenous steroids (mean cortisol 45.5 micrograms/100 ml cytosol) as well as inactivation of receptor secondary to the illness. Thus, the lung of the human fetus and neonate contains the receptor mechanism necessary for direct responsiveness to glucocorticoids. These findings support the potential usefulness of these hormones in prevention of respiratory distress syndrome in the premature infant.Keywords
This publication has 21 references indexed in Scilit:
- Lecithin/sphingomyelin ratios in amniotic fluid in normal and abnormal pregnancyAmerican Journal of Obstetrics and Gynecology, 1973
- Induction of Choline Phosphotransferase and Lecithin Synthesis in the Fetal Lung by CorticosteroidsScience, 1973
- Glucocorticoid-binding proteins of rat liver cytosol. I. Separation and identification of the binding proteins.1972
- A CONTROLLED TRIAL OF ANTEPARTUM GLUCOCORTICOID TREATMENT FOR PREVENTION OF THE RESPIRATORY DISTRESS SYNDROME IN PREMATURE INFANTSPediatrics, 1972
- Role of DNA and Specific Cytoplasmic Receptors in Glucocorticoid ActionProceedings of the National Academy of Sciences, 1972
- Glucocorticoid-receptor complexes and the earliest steps in the action of glucocorticoids on thymus cellsJournal of Steroid Biochemistry, 1972
- Specific binding of glucocorticoids in vitro in the soluble fraction of mouse fibroblastsBiochemistry, 1972
- Specific Cytoplasmic Glucocorticoid Hormone Receptors in Hepatoma Tissue Culture CellsProceedings of the National Academy of Sciences, 1971
- Acceleration of appearance of pulmonary surfactant in the fetal lamb by administration of corticosteroids.Published by Elsevier ,1970
- Precocious induction of retinal glutamine synthetase by hydrocortisone in the embryo and in culture. Age-dependent differences in tissue responseBiochimica et Biophysica Acta (BBA) - General Subjects, 1967