Hypothyroidism alters the expression of prostaglandin D-2 synthase beta trace in specific areas of the developing rat brain

Lipocalin-type prostaglandin D-2 synthase is the enzyme responsible for the synthesis of prostaglandin Dg, a major prostaglandin in the central nervous system. We analysed the effects of thyroid hormone deprivation on prostaglandin D-2 synthase gene expression in the developing rat brain. By in situ hybridization, the strongest prostaglandin D-2 synthase mRNA signal was detected in the leptomeninges and choroid plexus. The signal was greatly reduced in the cerebellar interlaminar meninges of hypothyroid rats aged 15 and 25 days. Immunohistochemical studies defined changes in the location of the prostaglandin Dp synthase protein. In control but not in hypothyroid animals, Cajal-Retzius neurons of cortical layer I, and pyramidal cortical plate neurons were intensely stained on postnatal day 5. Conversely, prostaglandin Dp synthase protein levels were higher in neurons of the CA1 and CA3 regions and the dentate gyrus of the hippocampus of hypothyroid animals on postnatal days 5, 15 and 25, and also in subplate neurons on postnatal days 15 and 25, In agreement with the in situ hybridization and northern blotting data, the major difference was found in the cerebellar interlaminar meninges of hypothyroid animals, where the protein was clearly down-regulated on postnatal days 15 and 25. These results show that hypothyroidism causes both age-and region-specific alterations in the expression and location of the prostaglandin Dp synthase during postnatal brain development, probably reflecting a cell-specific regulatory effect of thyroid hormone on the prostaglandin Da synthase.