THE ONTOGENY OF CEREBRAL AND CEREBELLAR NITRIC-OXIDE SYNTHASE IN THE GUINEA-PIG AND RAT

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. I n the guinea pig, NOS increased from an almost undetectable level at 0 .49 of gestation (31 d), reaching adult levels before birth and peakin g at 140% of the adult activity (forebrain) or 250% of the adult activ ity (cerebellum) in the week after birth. The rise in fetal NOS activi ty followed the reported rise in the estrogen receptor concentration i n the brain and could be reduced by treatment of the guinea pig at ful l term with tamoxifen, implicating estrogens in the expression of feta l NOS activity, In the rat, brain NOS activity did not rise significan tly until after birth, reaching adult levels approximately 2 wk after birth, and rising to 150 or 130% of the adult activity in the forebrai n and cerebellum, respectively, at 4 wk after birth. The appearance of NOS activity in the rat also followed the reported appearance of estr ogen receptors in the brain. In both species the appearance of high NO S activity in the brain immediately precedes the period in which maxim al synaptogenesis occurs: immediately before birth in the guinea pig a nd 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 syn aptogenesis in the developing brain.