Urinary excretion rates of 15 free steroids: potential utility in differential diagnosis of Cushing's syndrome.

Glucocorticoids (GCs) induce surfactant synthesis in the late foetal lung. Deficient GC action causes respiratory distress syndrome (RDS). 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. Reduction or loss of pulmonary 11beta-HSD1 activity in glycyrrhetinic acid-treated rats substantially impaired foetal lung maturation (Hundertmark et al., Horm Metab Res, this issue). To test these data, we investigated 11beta-HSD1 activity and lung maturity in the late foetal lung using 11beta-HSD1 knockout mice. Control foetal mice showed high 11beta-HSD activity in the late foetal lung and levels of plasma 11-dehydrocorticosterone were high. Lungs from 11beta-HSD1 -/- mice had lower surfactant protein-A (mRNA and protein) levels and significant depletion of lung surfactant according to both light and electron microscopy, and also had reduced amniotic fluid lecithin/sphingomyelin ratios. These results support the previous experiments with glycyrrhetinic acid and emphasize the importance of 11beta-HSD1 in foetal lung maturation.

“…Corticosterone and 11-dehydrocorticosterone assays Foetal blood was collected at decapitation. Corticosterone and 11-dehydrocorticosterone [3] were quantified as described [1].…”

Section: Abstract 111146 • 11b-hydroxysteroid Dehydrogenase • Ec mentioning

confidence: 99%

Foetal Lung Maturation in 11β-Hydroxysteroid Dehydrogenase Type 1 Knockout Mice

Hundertmark¹,

Dill²,

Ebert³

et al. 2002

“…Corticosterone, 11-dehydrocorticosterone and GE assays Fetal blood was collected at decapitation. Corticosterone, 11-dehydrocorticosterone [23] and GE [24] were quantified, as described.…”

Section: Animalsmentioning

confidence: 99%

11β-Hydroxysteroid Dehydrogenase Type 1: A New Regulator of Fetal Lung Maturation

Hundertmark

Dill²,

Bühler³

et al. 2002

Glucocorticoids (GCs) induce surfactant synthesis in the late fetal lung. Deficient GC action causes respiratory distress syndrome. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. We investigated 11beta-HSD1 in the late fetal lung using the licorice-derived inhibitor, glycyrrhetinic acid (GE), in pregnant rats (day 13 of gestation until term). Control fetal mice and rats showed high 11beta-HSD activity in the late fetal lung; levels of plasma 11-dehydrocorticosterone were also high. Reduction/loss of pulmonary 11beta-HSD1 activity in GE-treated rats substantially impaired fetal lung maturation. Lungs from GE-exposed rats had lower surfactant protein-A (mRNA and protein) levels and reduced amniotic fluid lecithin/sphingomyelin ratios. There was a marked depletion of lung surfactant before and after birth, as detected by both light and electron microscopy. The data emphasize the importance of 11beta-HSD1 in amplifying key GC-dependent maturational processes in the late fetal lung.

“…The gestational age of samples varied between 21 and 38 completed weeks of pregnancy. Steroids were quantified as described [26,27].…”

Section: Cortisol and Cortisone Concentrations In Human Amniotic Fluidmentioning

confidence: 99%

Ontogeny of 11β-Hydroxysteroid Dehydrogenase: Activity in the Placenta, Kidney, Colon of Fetal Rats and Rabbits

Hundertmark

Bühler²,

Fromm³

et al. 2001

Mechanisms to regulate closely fetal GC exposure are of considerable importance, as certain organs (kidney, brain) are adversely affected by excess GCs. 11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) reduces transplacental passage of maternal GCs to the fetus. We hypothesized that 11beta-HSD2, if active in fetal kidney and colon, might allow local tissue modulation of GC access during the critical last trimester. We determined the presence, ontogeny and functionality of 11beta-HSD in the placenta and fetal, neonatal and adult kidney and colon in rats and rabbits and the cortisol:cortisone ratio in human amniotic fluid, which represents fetal urine. There was clear a 11beta-HSD2 expression in last trimester fetal colon, kidney and placenta in both rats and rabbits. This appeared of functional importance, since the potency of cortisol on fetal rabbit colonic sodium flux in the Ussing chamber was increased by 11beta-HSD inhibition. In human amniotic fluid, we found a decreasing ratio of cortisol:cortisone across the last trimester, suggesting an analogous onset of renal 11beta-HSD2 activity in the human fetal kidney. Local fetal tissue 11beta-HSD2 may modulate exposure to the deleterious effects of GCs upon target tissue maturation during sensitive periods of late gestation when fetal GC levels rise to prepare other organs (lung) for adaptations at birth.