Actions of hypoxia on catecholamine synthetic enzyme mRNA expression before and after development of adrenal innervation in the sheep fetus

1.We have investigated adrenal mRNA expression of the catecholamine synthet ic enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransfe rase (PNMT) following acute hypoxia in fetal sheep before (< 105 days gesta tion, n = 20) and after (> 125 days gestation, n = 20) the development of a drenal innervation and following pretreatment with the nicotinic receptor a natgonist hexamethonium (n = 12). 2. Total RNA was extracted from fetal adrenal glands collected at specific time points at 3-20 h after the onset of either hypoxia (similar to 50% red uction in fetal arterial oxygen saturation (S-O2) for 30 min), or normoxia. 3. Before 105 days, there was a decrease in adrenal TH mRNA expression at 2 0 h after hypoxia and adrenal TH mRNA expression was directly related to th e changes in arterial Po, measured during normoxia and hypoxia. After 125 d ays, adrenal TH mRNA levels were suppressed for up to 12 h following hypoxi a. 4. In both age groups, adrenal PNMT mRNA expression increased at 3-5 h afte r hypoxia and was inversely related to the changes in fetal arterial Po, du ring normoxia or hypoxia. 5. After 125 days, the administration of hexamethonium (25 mg kg(-1), I.V.) reduced TH mRNA but not PNMT mRNA expression after normoxia. After hexamet honium pretreatment, there was no significant change in either adrenal TH o r PNMT mRNA expression following hypoxia. 6. We conclude that acute hypoxia differentially regulates adrenal TH and P NMT mRNA expression in the fetal sheep both before and after the developmen t of adrenal innervation. After the development of adrenal innervation, how ever, the effect of acute hypoxia upon adrenal TH and PNMT mRNA expression is dependent upon neurogenic input acting via nicotinic receptors.