PROSTAGLANDIN-H SYNTHASE-1 (PGHS-1) GENE IS EXPRESSED IN SPECIFIC NEURONS OF THE BRAIN OF THE LATE-GESTATION OVINE FETUS

Prostaglandin (PG) E(2) acts on the brain stem to modulate breathing a ctivity in the ovine fetus. The source of this PGE(2) is unknown and w e hypothesized that it is produced locally in the developing brain and functions in a paracrine and/or autocrine manner. The purpose of the present study was to establish whether prostaglandin-H synthase-1 (PGH S-1), a crucial enzyme in de novo prostaglandin synthesis, is present and its gene expressed in the ovine fetal brain. Immunohistochemical a nd molecular hybridization techniques were used to identify sites of P GHS-1 immunoreactivity and PGHS-1 mRNA expression respectively in the brain of the ovine fetus in late gestation (approximately 126 days ges tation, term 145 days). PGHS-1 immunoreactivity was localized to speci fic regions of the fetal brain, including the cortex, hypothalamus, hi ppocampal formation, superior colliculus of the midbrain, parabrachial nucleus of the pens, and the reticular formation, raphe, nucleus of t he solitary tract, and gracile and cuneate nuclei of the medulla. The relative abundance of PGHS-1 mRNA in selected brain regions, as determ ined by Northern blot analysis, correlated qualitatively with the numb er of PGHS-1 immunoreactive neurons identified in each region, In situ hybridization demonstrated PGHS-1 mRNA to be localized in the same ne urons or nuclei as PGHS-1 immunoreactivity. These results indicate tha t PGHS-1 is synthesized de novo in many brain regions including two th at are important in respiratory control: the pneumotaxic center (parab rachial nucleus) and the dorsal respiratory group (nucleus tractus sol itarius) suggesting that prostaglandins that modulate fetal respirator y activity are synthesized endogenously.