PMID- 9135697
OWN - NLM
STAT- MEDLINE
DCOM- 19970528
LR  - 20220331
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 46
IP  - 2
DP  - 1997 Feb
TI  - Placental 11 beta-hydroxysteroid dehydrogenase: a key regulator of fetal 
      glucocorticoid exposure.
PG  - 161-6
AB  - 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. DESIGN: 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. CONCLUSION: 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.
FAU - Benediktsson, R
AU  - Benediktsson R
AD  - University Department of Medicine, Western General Hospital, Edinburgh, Scotland, 
      UK. R.Benediktsson@ed.ac.uk
FAU - Calder, A A
AU  - Calder AA
FAU - Edwards, C R
AU  - Edwards CR
FAU - Seckl, J R
AU  - Seckl JR
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (Anti-Inflammatory Agents)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - P540XA09DR (Glycyrrhetinic Acid)
RN  - V27W9254FZ (Cortisone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Administration, Topical
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Cortisone/*metabolism
MH  - Female
MH  - Glycyrrhetinic Acid/pharmacology
MH  - Humans
MH  - Hydrocortisone/*metabolism
MH  - Hydroxysteroid Dehydrogenases/antagonists & inhibitors/*metabolism
MH  - Organ Culture Techniques
MH  - Perfusion
MH  - Placenta/*enzymology
EDAT- 1997/02/01 00:00
MHDA- 1997/02/01 00:01
CRDT- 1997/02/01 00:00
PHST- 1997/02/01 00:00 [pubmed]
PHST- 1997/02/01 00:01 [medline]
PHST- 1997/02/01 00:00 [entrez]
AID - 10.1046/j.1365-2265.1997.1230939.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 1997 Feb;46(2):161-6. doi: 
      10.1046/j.1365-2265.1997.1230939.x.