Ontogenesis and sex differences in rabbit fetal adrenal phenylethanolamine N-methyltransferase

The development of the sympatho-adrenal system is important for neonatal adaptation to extrauterine life. On the basis of previous studies suggesting relatively accelerated adrenal maturation in the female rabbit fetus, we conducted an ontogenetic study of male-female differences in adrenal levels of phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme in epinephrine biosynthesis. Geometric mean adrenal PNMT activities increased significantly from 5.1 +/- 0.07 pmol/pair adrenals/h for females and 3.3 +/- 1.21 for males at 24 days gestation to 32.1 +/- 1.07 for females and 29.2 +/- 1.08 for males at 31 days gestation. These increases with gestational age were highly significant (p less than 0.001). Analysis of variance showed significantly increased activity in female versus male littermates (p less than 0.025). No significant differences were noted among the female fetuses grouped according to their numbers of male neighbors. These results demonstrate that adrenal PNMT increases significantly with advancing gestational age and that female fetuses have significantly increased activity relative to their male littermates. The near neighbor fetal data do not suggest that this effect is mediated by a humoral agent which is transferable by the uterine vasculature or by interamniotic diffusion. We speculate that sex differences in sympathoadrenal development may explain the lower neonatal morbidity and mortality in female infants.