Effect of Prenatal Glucocorticoid Treatment on Adrenal Phenylethanolamine N‐methyltransferase Gene Expression in the Adult Wistar‐Kyoto Rat

• Published in: The FASEB journal 2010-04, Vol.24 (S1), p.lb577-lb577
• Main Authors: Nguyen, Phong, Peltsch, Heather, Crispo, James, Wit, Jose, Ubriaco, Gino, Ansell, Dominique, Wall, Vanessa, Eibl, Joseph, Tai, T.C.
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.24.1_supplement.lb577

Prenatal exposure to glucocorticoids (GCs) programs for hypertension later in life. The current study examined the impact of prenatal GC exposure on the post‐natal regulation of the gene encoding for phenylethanolamine N‐methyltransferase (PNMT), the enzyme involved in the biosynthesis of the catecholamine, epinephrine. PNMT has been linked to hypertension and is elevated in animal models of hypertension. Results from this study show that systolic, diastolic and mean arterial blood pressure are elevated in male offspring (5 to 17 weeks of age) from dams treated with dexamethasone (DEX, +15%) or corticosterone (CORT, +12%) compared to male offspring from saline‐treated (SAL) dams. RT‐PCR analysis shows that adrenal PNMT mRNA is 1.5‐fold higher in DEX and CORT males compared to SAL males. RT‐PCR analysis of transcriptional regulators of the PNMT gene show that prenatal GC exposure increased mRNA levels of Egr‐1 (2.5‐fold), AP‐2 (1.9‐fold) and GR (2.0‐fold). In contrast, Western blot analyses show increased expression of PNMT protein (1.44‐fold, DEX), along with increased Egr‐1 (1.5 fold, DEX and CORT), AP‐2 (1.4 fold, CORT), and GR (1.7 fold, DEX and CORT) compared to SAL males. These results suggest that increased PNMT gene expression via altered transcriptional activity is a mechanism by which prenatal GC insult may program for hypertension later in life.