Perinatal changes in choroidal 15-hydroxyprostaglandin dehydrogenase: implications for prostaglandin removal from brain.
We have previously shown in the sheep fetus at 0.7 and 0.9 gestation that the choroid plexus, unlike brain parenchyma, catabolizes prostaglandins (PGs). Peculiarly, in the choroid plexus, PGE(2) catabolism persists throughout the neonatal period to abate in the adult, while PGF(2alpha) catabolism abates shortly after birth. To explain this differential behavior and elucidate the function of catabolic enzymes, we examined the cellular location and activity of the rate-limiting enzyme for PGE(2) and PGF(2alpha) catabolism, 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Immunofluorescence histochemistry and immunogold electronmicroscopy revealed abundant 15-PGDH expression in the epithelial cytosol close to the brush-border membrane at 0.7 and 0.9 gestation. In contrast, at 5 and 15 days postnatal, 15-PGDH was found throughout the cytosol of stromal fibroblasts. No staining was observed at either location in pregnant adults. PGF(2alpha) catabolism was minimal in the total homogenate and 100000xg supernatant of the fetal choroid plexus at 0.7 and 0.9 gestation, while PGE(2) catabolism was evident at 0.7 gestation only. In contrast, both PGs were catabolized in minced specimens at either age. In conclusion, our study shows immunoreactive 15-PGDH in the choroid plexus from fetal and neonatal, but not pregnant adult, sheep. Results suggest that PGE(2) catabolism is not as critically dependent as that of PGF(2alpha) on tissue integrity and 15-PGDH location. Given the key role being assigned to the choroid plexus in PG removal from brain, we speculate that persistence of PGE(2) catabolism into the early postnatal period protects against central respiratory depression caused by the compound during this susceptible stage of development.
Krunic
N
N
Integrative Biology Programme, The Hospital for Sick Children, Ontario, Toronto, Canada.
Adamson
S L
SL
Ackerley
C
C
Okita
R T
RT
Coceani
F
F
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry / Q000502:physiology; D002831:Choroid Plexus / Q000196:embryology* / Q000201:enzymology* / Q000648:ultrastructure; D015232:Dinoprostone / Q000378:metabolism*; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005455:Fluorescent Antibody Technique; D006911:Hydroxyprostaglandin Dehydrogenases / Q000032:analysis / Q000378:metabolism*; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D011247:Pregnancy; D012756:Sheep; D017154:Stromal Cells / Q000201:enzymology; D013347:Subcellular Fractions / Q000201:enzymology
D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone