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-secretion-synthesis coupling occurs through transsynaptic (neuronal) activity. In contrast, in the immature animal, before functional adrenal innervation, certain stressors (hypoglycemia and glycopenia) do not result in CA release. Additionally, it is not known whether release and biosynthesis remain coupled in the neonate as they are in the adult. Therefore, 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 either hypoxic, hypoglycemic, or cellularly glycopenic (2-deoxyglucose). Neither hypoxic stress nor insulin-induced hypoglycemic stress altered steady state levels of TH mRNA in the neonate. However, cellular glycopenia resulted in a significant 2-fold rise in TH mRNA levels (p < 0.05). As expected, each of these stressors increased TH mRNA levels in the mature adult rat. Thus, neonatal hypoxia and hypoglycemia appear to require intact neurogenic impulse activity, whereas cellular glycopenia may "directly" induce TH RNA, perhaps through hormonal mechanisms. This developmental model allows for the analysis of mechanisms governing adrenal CA release separate from those governing biosynthesis at the level of TH RNA. Acute neonatal hypoxic stress results in adrenal CA release without increasing TH RNA. Intrauterine growth retardation from chronic prenatal hypoxemia results in neonatal CA depletion and decreased CA responsiveness. We speculate that chronic hypoxia alters CA pathways, increasing the susceptibility of these infants to later stressors.
DeCristofaro
J D
JD
Department of Pediatrics, State University of New York at Stony Brook 11794-8111.
LaGamma
E F
EF
D000222:Adaptation, Physiological; D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007003:Hypoglycemia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism*