Sex differences in response to steroids in preterm sheep lungs are not explained by glucocorticoid receptor number or binding affinity

We recently reported that prenatal glucocorticoid therapy is less effective at promoting an improvement in lung function in male than in female sheep. This observation, and the higher incidence of respiratory distress syndrom e in human males, suggests that the male fetal lung may be less responsive to glucocorticoids than is the female fetal lung. Since glucocorticoids are known to exert their effects via specific cytoplasmic glucocorticoid recep tors (GR), we hypothesized that there may be sexual dimorphism in either th e number or binding affinity of lung GR. To test the hypothesis, binding of dexamethasone (a synthetic glucocorticoid, 0.5-40 nM) by cytosolic fractio ns of male (n = 16) and female (n = 16) fetal sheep lung was measured at 12 5 days gestation (term = 148 days). Scatchard analysis of dexamethasone binding showed that the total number of GR (Bmax) did not significantly differ between male (346 +/- 42 fmol/mg pr otein) and female (277 +/- 23 fmol/mg protein) fetuses. The measured bindin g affinity (Kd) in male fetal lungs (6.85 +/- 0.43 nM) was not significantl y different from that in females (8.46 +/- 1.02 nM). In conclusion, this study suggests: that sex differences in fetal sheep lun g responses to glucocorticoid therapy are not due to differences in the num ber or binding affinity of lung GR. (C) Wiley-Liss, Inc.