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

Abstract:

: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.

journal_name

Pediatr Pulmonol

journal_title

Pediatric pulmonology

authors

Kovar J,Waddell BJ,Sly PD,Willet KE

doi

10.1002/ppul.1082

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

8-13

issue

1

eissn

8755-6863

issn

1099-0496

pii

10.1002/ppul.1082

journal_volume

32

pub_type

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