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REGULATION OF ADRENAL PHENYLETHANOLAMINE N‐METHYLTRANSFERASE GENE EXPRESSION IN A FETAL PROGRAMMING MODEL OF HYPERTENSION
Author(s) -
Khurana Sandhya,
Nguyen Phong,
Grandbois Julie,
Peltsch Heather,
Lo Suet,
Venkataraman Krishnan,
Tai T.C.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.908.2
Subject(s) - phenylethanolamine , phenylethanolamine n methyltransferase , endocrinology , medicine , epinephrine , offspring , fetus , prenatal stress , gene expression , prenatal development , messenger rna , catecholamine , glucocorticoid , blood pressure , methyltransferase , biology , gene , pregnancy , dopamine , tyrosine hydroxylase , genetics , methylation
Prenatal exposure to elevated levels of glucocorticoids (GC) 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 the current study show that systolic, diastolic and mean arterial blood pressure were elevated in male WKY rat offspring (5 to 17 weeks of age) from dams treated with dexamethasone (DEX, +15%). Adrenal PNMT mRNA was elevated (1.5‐fold) in prenatally DEX‐exposed rats at 17 wks. Analysis of transcriptional regulators of the PNMT gene show that prenatal GC exposure increased mRNA levels of Egr‐1, AP‐2 and GR. Similar increased expression of PNMT protein, along with increased Egr‐1, AP‐2, and GR protein levels were also observed. Furthermore, GMSA showed increased binding of Egr‐1 and GR to the PNMT promoter. 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. (Research Funded by CIHR)