DIFFERENTIAL-EFFECTS OF INCREASING GESTATIONAL-AGE AND PLACENTAL RESTRICTION ON TYROSINE-HYDROXYLASE, PHENYLETHANOLAMINE N-METHYLTRANSFERASE, AND PROENKEPHALIN A MESSENGER-RNA LEVELS IN THE FETAL SHEEP ADRENAL

We have demonstrated that there are differential changes in the levels of tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT), and proenkephalin A (Pro Enk A) mRNA in the fetal sheep adrena l during late gestation. Adrenal TH mRNA:18S rRNA ratios increased bet ween gestational days 100 (0.98 +/- 0.13; n = 6) and 125 (1.40 +/- 0.1 5; n = 6) and then decreased, whereas adrenal PNMT mRNA:18S rRNA ratio s increased regularly between gestational days 100 (0.08 +/- 0.01) and 146 (0.17 +/- 0.03). The ratio of adrenal Pro Enk A mRNA to 18S rRNA was higher at gestational day 125 (0.085 +/- 0.005) than at either 80- 100 days (0.038 +/- 0.007) or 140-146 days of gestation (0.055 +/- 0.0 13). In 12 ewes, the growth and development of the placenta were restr icted (placental restriction group) from conception. The ratio of adre nal PNMT mRNA to 18S rRNA was significantly reduced in the placental r estriction group of fetal sheep (0.003 +/- 0.002) compared with contro ls (0.011 +/- 0.002), and there was a significant correlation between the ratio of adrenal PNMT mRNA to 18S rRNA and the mean arterial Po-2 (r = 0.88, p < 0.0005). In contrast, TH mRNA and Pro Enk mRNA were una ffected by placental restriction. Adrenaline and noradrenaline synthes es are therefore differentially regulated in the adrenal during late g estation and in response to chronic intrauterine hypoxemia.