Differential expression of the enzymatic system controlling synthesis, metabolism, and transport of PGF2 alpha in human fetal membranes.
The present study investigated the expression of genes and proteins associated with PGF2alpha biosynthesis, catabolism, and transport in matched amnion and choriodecidua of human term placenta. The concentration of PGF2alpha within fetal membranes depends on the balance between complex enzymatic systems responsible for, respectively, its synthesis-by prostaglandin-endoperoxide synthase 2 (PTGS2) and members of the aldo-keto reductase (AKR) family, AKR1C3 and AKR1B1-and its catabolic inactivation-through hydroxy-prostaglandin-dehydrogenase (HPGD). We observed that AKR1C3 shows equal basal expression (mRNA and protein) in choriodecidua and amnion but that AKR1B1 exhibits preferential expression in the choriodecidua. Expression of HPGD and solute carrier organic anion transporter family member 2A1 (SLCO2A1) was found primarily in the choriodecidua. We also evaluated whether an inflammatory environment induced by the gram-negative bacterial endotoxin lipopolysaccharide (LPS) affects expression of each candidate enzymes. The amnion responded to LPS with a small but significant decrease of AKR1B1 mRNA expression. In contrast, we found a significant increase in PTGS2 and AKR1C3 mRNA expression in choriodecidua after LPS challenge, but such regulation was confirmed only at protein levels for PTGS2 and not for AKR1C3. Our results suggest that the choriodecidua appears to be the main tissue, which expresses maximally all the components (synthesis, degradation, and transport) controlling PGF2alpha levels.
Breuiller-Fouché
Michelle
M
INSERM U767, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris, France.
Leroy
Marie-Josèphe
MJ
Dubois
Olivier
O
Reinaud
Pierrette
P
Chissey
Audrey
A
Qi
Hong
H
Germain
Guy
G
Fortier
Michel A
MA
Charpigny
Gilles
G
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000074425:Aldo-Keto Reductase Family 1 Member C3; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000201:enzymology*; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D027361:Organic Anion Transporters / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism
D008070:Lipopolysaccharides; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C503526:SLCO2A1 protein, human; D015237:Dinoprost; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human