PMID- 9348222
OWN - NLM
STAT- MEDLINE
DCOM- 19971124
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 138
IP  - 11
DP  - 1997 Nov
TI  - Differential regulation of 11 beta-hydroxysteroid dehydrogenase type 1 and 2 by 
      nitric oxide in cultured human placental trophoblast and chorionic cell 
      preparation.
PG  - 4912-20
AB  - Two types of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) have been 
      identified in different tissues. Type 1 has both oxidase and reductase activities 
      interconverting cortisol and cortisone, whereas type 2 has only oxidase activity 
      converting cortisol to cortisone. It has been proposed that placental 11 beta-HSD 
      controls the passage of maternal glucocorticoids to the fetal circulation. 
      However, little is known about the regulation of 11 beta-HSD in the human 
      placenta and fetal membranes. We cultured human term placental trophoblast and 
      chorionic trophoblast cells to examine effects of nitric oxide donors, sodium 
      nitroprusside (SNP) and S-nitroso-N-acetyl penicillamine (SNAP), on the activity 
      and messenger RNA (mRNA) expression of 11 beta-HSD. At 72 h of culture, placental 
      trophoblast formed syncytial clumps that were cytokeratin positive and displayed 
      mainly type 2 oxidase activity, although some type 1 reductase activity was 
      detectable. Chorion preparations contain greater than 90% trophoblast cells as 
      demonstrated by immunostaining for cytokeratin and less than 5% vimentin positive 
      cells. Type 1 reductase activity predominated in the chorionic trophoblast cells 
      with barely detectable type 1 or type 2 oxidase activity. Both SNP (1-400 microM) 
      and SNAP (1 mM) inhibited placental 11 beta-HSD type 2 oxidase activity but not 
      type 1 reductase activity either in placental or chorionic cells. An inhibitory 
      effect on type 2 oxidase activity was reproduced in part by 8-bromo cGMP, blocked 
      partially by the guanylate cyclase inhibitor LY83583 (1 microM), but not by an 
      ADP-ribosylation inhibitor N, N'-hexamethylene-bis-acetamide (HMBG) (10 mM). SNP 
      also suppressed the expression of type 2 mRNA in cultured placental trophoblast 
      in a dose-dependent manner, and this effect was also blocked by LY83583. We 
      conclude that human placental trophoblast possesses predominantly 11 beta-HSD 
      type 2 oxidase activity, whereas chorionic cells possess mainly type 1 reductase 
      activity under the culture conditions employed. Nitric oxide specifically 
      attenuated 11 beta-HSD type 2 oxidase activity as well as its mRNA expression in 
      the placental trophoblast. The effect was mediated at least partially through the 
      cGMP pathway, although an alternative pathway other than ADP-ribosylation may 
      exist.
FAU - Sun, K
AU  - Sun K
AD  - Department of Physiology, University of Toronto, Ontario, Canada. 
      kang.sun@utoronto.ca
FAU - Yang, K
AU  - Yang K
FAU - Challis, J R
AU  - Challis JR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - 169D1260KM (Nitroprusside)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 79032-48-7 (S-Nitroso-N-Acetylpenicillamine)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - GNN1DV99GX (Penicillamine)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Adult
MH  - Cells, Cultured
MH  - Chorion/cytology/*enzymology
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Humans
MH  - Hydroxysteroid Dehydrogenases/genetics/*metabolism
MH  - Isoenzymes/genetics/*metabolism
MH  - Kinetics
MH  - Nitric Oxide/*physiology
MH  - Nitroprusside/pharmacology
MH  - Penicillamine/analogs & derivatives/pharmacology
MH  - Placenta/*cytology
MH  - RNA, Messenger/metabolism
MH  - S-Nitroso-N-Acetylpenicillamine
MH  - Trophoblasts/*enzymology
EDAT- 1997/11/05 00:00
MHDA- 1997/11/05 00:01
CRDT- 1997/11/05 00:00
PHST- 1997/11/05 00:00 [pubmed]
PHST- 1997/11/05 00:01 [medline]
PHST- 1997/11/05 00:00 [entrez]
AID - 10.1210/endo.138.11.5544 [doi]
PST - ppublish
SO  - Endocrinology. 1997 Nov;138(11):4912-20. doi: 10.1210/endo.138.11.5544.