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 t he 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(2 alpha) catabolism a bates shortly after birth. To explain this differential behavior and elucid ate the function of catabolic enzymes, we examined the cellular location an d activity of the rate-limiting enzyme for PGE(2) and PGF(2 alpha) cataboli sm, 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Immunofluorescence his tochemistry and immunogold electronmicroscopy revealed abundant 15-PGDH exp ression 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 fo und throughout the cytosol of stromal fibroblasts. No staining was observed at either location in pregnant adults. PGF(2 alpha) catabolism was minimal in the total homogenate and 100 000Xg supernatant of the fetal choroid ple xus at 0.7 and 0.9 gestation, while PGE(2) catabolism was evident at 0.7 ge station only. In contrast, both PGs were catabolized in minced specimens at either age. In conclusion, our study shows immunoreactive 15-PGDH in the c horoid plexus from fetal and neonatal, but not pregnant adult, sheep. Resul ts suggest that PGE(2) catabolism is not as critically dependent as that of PGF(2 alpha) 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 prot ects against central respiratory depression caused by the compound during t his susceptible stage of development. (C) 2000 Elsevier Science B.V. All ri ghts reserved.