M. Venihaki et al., Circadian rise in maternal glucocorticoid prevents pulmonary dysplasia in fetal mice with adrenal insufficiency, P NAS US, 97(13), 2000, pp. 7336-7341
Citations number
42
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
The hypothalamic-pituitary-adrenal (HPA) axis, including hypothalamic corti
cotropin-releasing hormone (CRH) and pituitary corticotropin, is one of the
first endocrine systems to develop during fetal life, probably because glu
cocorticoid secretion is necessary for the maturation of many essential fet
al organs. Consistent with this. pregnant mice with an inactivating mutatio
n in the Crh gene deliver CRH-deficient offspring that die at birth with dy
splastic lungs, which can be prevented by prenatal maternal glucocorticoid
treatment. But children lacking the ability to synthesize cortisol (because
of various genetic defects in adrenal gland development or steroidogenesis
) are not born with respiratory insufficiency or abnormal lung development,
suggesting that the transfer of maternal glucocorticoid across the placent
a might promote fetal organ maturation in the absence of fetal glucocortico
id production. We used pregnant mice with a normal HPA axis carrying fetuse
s with CRH deficiency to characterize the relative contributions of the fet
al and maternal adrenal to the activity of the fetal HPA axis, and related
these findings to fetal lung development. We found that in the presence of
fetal adrenal insufficiency, normal fetal lung development is maintained by
the transfer of maternal glucocorticoid to the fetus, specifically during
the circadian peak in maternal glucocorticoid secretion.