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The appearance of nitric oxide synthase (NOS, EC 1.14.13.39) activity in the brain of fetal and neonatal guinea pigs and rats was studied. In the guinea pig, NOS increased from an almost undetectable level at 0.49 of gestation (31 d), reaching adult levels before birth and peaking at 140% of the adult activity (forebrain) or 250% of the adult activity (cerebellum) in the week after birth. The rise in fetal NOS activity followed the reported rise in the estrogen receptor concentration in the brain and could be reduced by treatment of the guinea pig at full term with tamoxifen, implicating estrogens in the expression of fetal NOS activity. In the rat, brain NOS activity did not rise significantly until after birth, reaching adult levels approximately 2 wk after birth, and rising to 150 or 130% of the adult activity in the forebrain and cerebellum, respectively, at 4 wk after birth. The appearance of NOS activity in the rat also followed the reported appearance of estrogen receptors in the brain. In both species the appearance of high NOS activity in the brain immediately precedes the period in which maximal synaptogenesis occurs: immediately before birth in the guinea pig and 2-3 wk after birth in the rat. Thus the appearance of a functional estrogen-estrogen receptor system in the brain may be responsible, at least in part, for the expression of a high activity of NOS, which in turn may play important roles in promoting cerebral blood flow and synaptogenesis in the developing brain.

The Ontogeny of Cerebral and Cerebellar Nitric Oxide Synthase in the Guinea Pig and Rat