Prostaglandin biosynthesis and catabolism in the developing fetal sheep brain

The biosynthesis of prostaglandins E2 and F2alpha as well as the catabolism of [9beta- 3H1]prostaglandin F2alpha by homogenates of whole brain from fetal and neonatal lambs was investigated. The biosynthetic measurements utilized the mass spectrometric deuterium isotope dilution-dual ion monitoring technique (Samulsson, B., Hamberg, M., and Sweeley, C.C. (1970) Anal. Biochem. 38, 301-304; Wolfe, L.S., and Pace-Asciak, C. (1972) in Prostaglandins in Fertility Control (Bergström, S., Green, K., and Samuelsson, B., eds) Vol. 2. pp. 201-207, WHO, Karolinska Institutet, Stockholm), whereas the activity of the catabolizing system was measured by the radiolabel dilution-thin layer chromatographic technique reported previously (Pace-Asciak, C. (1975) J. Biol. Chem. 250, 2795-2800). The structures of all products were confirmed by mass spectrometry. Early fetal brain (gestational age 30 to 32 days) contained the highest activity of NAD-dependent prostaglandin 15-hydroxy dehydrogenase which varied inversely with age of the fetus, dropping to almost undetectable levels by neonatal Day 4. Both prostaglandins E2 and F2alpha, were formed by brain from all ages tested and the total prostaglandins formed rose gradually with age. Thus, the period of maximal prostaglandin catabolism which we term the "critical prostaglandin period" appears in the fetal lamb brain around 30 days gestational age or earlier. These findins together with others previously reported by us in other tissues, support the concept that prostaglandin catabolism might play an important role in protecting the developing organ from possible adverse effects of locally formed or circulating prostaglandins. These adverse effects on the developing brain might relate to the known vasoconstrictor properties of the prostaglandins, as well as to their known effects on the induction of cell differentiation.