Adrenergic expression in the rat adrenal gland: multiple developmental regulatory mechanisms.

ABSTRACT

Phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) has been used as a marker to examine development of adrenergic expression in the rat adrenal gland and the putative role of glucocorticoids in this process. PNMT enzymatic activity increases 7-10-fold from birth to postnatal day 35. Immunotitration studies show that PNMT protein only increases 4-5-fold during this same time period. Moreover, the slopes from the immunotitration curves decrease with increasing age. Thus, a more active enzyme with lower affinity for the antiserum appears to be present in the older animals. Quantitative solution hybridization shows that PNMT mRNA increases 2.5-fold from birth through postnatal day 11. Thereafter, it declines, and eventually plateaus at values insignificantly different from birth by postnatal day 25. Northern analysis further shows that two forms of PNMT mRNA are expressed. Adrenal corticosterone remains low from birth through postnatal day 11, but then increases nearly 10-fold by adulthood. The lack of concordance between changes in PNMT activity, protein, and mRNA suggests that adrenergic expression is developmentally regulated at multiple levels; the above provides evidence for both transcriptional and post-transcriptional controls, since changes in PNMT mRNA may differ in both magnitude and direction from changes in PNMT activity and protein during the developmental window examined. These developmental regulatory mechanisms may be in part glucocortocoid-mediated, but corticosteroid control of PNMT gene expression does not appear to be the predominant mechanism of control.