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 syndrome 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 receptors (GR), we hypothesized that there may be sexual dimorphism in either the number or binding affinity of lung GR. To test the hypothesis, binding of dexamethasone (a synthetic glucocorticoid, 0.5-40 nM) by cytosolic fractions of male (n = 16) and female (n = 16) fetal sheep lung was measured at 125 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 protein) and female (277 +/- 23 fmol/mg protein) fetuses. The measured binding affinity (Kd) in male fetal lungs (6.85 +/- 0.43 nM) was not significantly different from that in females (8.46 +/- 1.02 nM). In conclusion, this study suggests that sex differences in fetal sheep lung responses to glucocorticoid therapy are not due to differences in the number or binding affinity of lung GR.
Kovar
J
J
Division of Clinical Sciences, Telethon Institute for Child Health Research, Perth, Australia. janak@ichr.uwa.edu.au
Waddell
B J
BJ
Sly
P D
PD
Willet
K E
KE
D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism* / Q000494:pharmacology; D007553:Isotope Labeling; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011869:Radioligand Assay; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D012727:Sex Characteristics; D012756:Sheep
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone