Ontogeny of 11beta-hydroxysteroid dehydrogenase: activity in the placenta, kidney, colon of fetal rats and rabbits.
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.
Hundertmark
S
S
Department of Obstetrics and Gynecology, Freie Universität Berlin, Germany. hundertmark@ukbf.fu-berlin.de
Bühler
H
H
Fromm
M
M
Kruner-Gareis
B
B
Kruner
M
M
Ragosch
V
V
Kuhlmann
K
K
Seckl
J R
JR
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003106:Colon / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism; D003348:Cortisone / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000494:pharmacology; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007668:Kidney / Q000196:embryology* / Q000201:enzymology; D009924:Organ Culture Techniques; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D012964:Sodium / Q000378:metabolism
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D012964:Sodium; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone; D006854:Hydrocortisone