NEONATAL STRESS - EFFECTS OF HYPOGLYCEMIA AND HYPOXIA ON ADRENAL TYROSINE-HYDROXYLASE GENE-EXPRESSION

Catecholamines (CA) are released from and resynthesized in the adrenal medulla in response to stress. In the mature animal, stimulus-secreti on-synthesis coupling occurs through transsynaptic (neuronal) activity . In contrast, in the immature animal, before functional adrenal inner vation, certain stressors (hypoglycemia and glycopenia) do not result in CA release. Additionally, it is not known whether release and biosy nthesis remain coupled in the neonate as they are in the adult. Theref ore, to evaluate whether neonatal stressors can induce CA biosynthesis at the genomic level ''directly'' before function adrenal innervation , we studied the expression of the tyrosine hydroxylase (TH) gene, the rate-limiting enzyme in CA biosynthesis. Newborn rat pups were made e ither hypoxic, hypoglycemic, or cellularly glycopenic (2-deoxyglucose) . Neither hypoxic stress nor insulin-induced hypoglycemic stress alter ed steady state levels of TH mRNA in the neonate. However, cellular gl ycopenia resulted in a significant 2-fold rise in TH mRNA levels (p < 0.05). As expected, each of these stressors increased TH mRNA levels i n the mature adult rat. Thus, neonatal hypoxia and hypoglycemia appear to require intact neurogenic impulse activity, whereas cellular glyco penia may ''directly'' induce TH RNA, perhaps through hormonal mechani sms. This developmental model allows for the analysis of mechanisms go verning adrenal CA release separate from those governing biosynthesis at the level of TH RNA. Acute neonatal hypoxic stress results in adren al CA release without increasing TH RNA. Intrauterine growth retardati on from chronic prenatal hypoxemia results in neonatal CA depletion an d decreased CA responsiveness. We speculate that chronic hypoxia alter s CA pathways, increasing the susceptibility of these infants to later stressors.