Placental 11 beta-hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure.
OBJECTIVE
Placental 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which converts active cortisol to inactive cortisone, has been proposed to be the mechanism guarding the fetus from the growth retarding effects of maternal glucocorticoids; however, other placental enzymes have also been implicated. Placental 11 beta-HSD is unstable in vitro, and enzyme activity thus detected may not be relevant to the proposed barrier role. We have therefore examined placental glucocorticoid metabolism in dually perfused freshly isolated intact human placentas.


METHODS
Placentas were obtained from randomly selected normal term deliveries. The maternal circuit was perfused with physiological concentration of cortisol, the fetal effluent collected and steroid metabolites separated and quantified using silica columns (Sep-pak Plus) and HPLC.


RESULTS
Most of the maternally administered cortisol was metabolized to cortisone, and no conversion of cortisone to cortisol was detected. Cortisone was the only product of cortisol metabolism. Inhibition of 11 beta-HSD with glycyrrhetinic acid allowed cortisol to gain direct access to the fetal circulation.


CONCLUSIONS
We conclude that human placental 11 beta-HSD plays a crucial role in controlling glucocorticoid access to the fetus. Other enzymes are not significant contributors at physiologically relevant cortisol concentrations.
Benediktsson
R
R
University Department of Medicine, Western General Hospital, Edinburgh, Scotland, UK. R.Benediktsson@ed.ac.uk
Calder
A A
AA
Edwards
C R
CR
Seckl
J R
JR
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003348:Cortisone / Q000378:metabolism*; D005260:Female; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009924:Organ Culture Techniques; D010477:Perfusion; D010920:Placenta / Q000201:enzymology*
D000893:Anti-Inflammatory Agents; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid; D003348:Cortisone; D006854:Hydrocortisone