Altered Adrenal Medulla Function in Fetal Sheep with Intrauterine Growth Restriction

Abstract

Intrauterine growth restriction is a development condition commonly associated with insufficient placental delivery of nutrient and oxygen to the fetus. Among the important adaptations by the fetus are elevated blood catecholamine concentrations. In the current study, we examined two potential pathways which may mediate the observed epinephrine and norepinephrine concentrations in the adrenal medulla. The first of which is the catecholamine synthesis pathway consisting of four enzymes: TH, DDC, DBH and PNMT. Contrary to our prediction, mRNA expression of all four enzymes decreased compared to the controls (p<0.05 for DDC and PNMT). Second, we predicted the α2 adrenergic receptors to be downregulated in response to chronic catecholamine exposure. Our results showed a statistically significant decrease in mRNA concentrations of the ADRα2C isoform of the receptor, supporting our hypothesis that chromaffin cells were desensitized to inhibitory adrenergic receptors. Although more studies are needed to fully characterize the mechanisms, we conclude that catecholamine production and autocrine inhibitory activity was impaired in adrenal chromaffin cells.