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 fo r the synthesis of prostaglandin Dg, a major prostaglandin in the cent ral nervous system. We analysed the effects of thyroid hormone depriva tion on prostaglandin D-2 synthase gene expression in the developing r at brain. By in situ hybridization, the strongest prostaglandin D-2 sy nthase mRNA signal was detected in the leptomeninges and choroid plexu s. The signal was greatly reduced in the cerebellar interlaminar menin ges of hypothyroid rats aged 15 and 25 days. Immunohistochemical studi es defined changes in the location of the prostaglandin Dp synthase pr otein. In control but not in hypothyroid animals, Cajal-Retzius neuron s of cortical layer I, and pyramidal cortical plate neurons were inten sely 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 postnat al days 5, 15 and 25, and also in subplate neurons on postnatal days 1 5 and 25, In agreement with the in situ hybridization and northern blo tting data, the major difference was found in the cerebellar interlami nar meninges of hypothyroid animals, where the protein was clearly dow n-regulated on postnatal days 15 and 25. These results show that hypot hyroidism causes both age-and region-specific alterations in the expre ssion and location of the prostaglandin Dp synthase during postnatal b rain development, probably reflecting a cell-specific regulatory effec t of thyroid hormone on the prostaglandin Da synthase.