title: Prenatal glucocorticoid exposure programs adrenal PNMT expression and adult hypertension.
abstract: Prenatal exposure to glucocorticoids (GCs) programs for hypertension later in life. The aim of the current study was to examine the impact of prenatal GC exposure on the postnatal 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. Male offspring of Wistar-Kyoto dams treated with dexamethasone (DEX) developed elevated systolic, diastolic and mean arterial blood pressure compared to saline-treated controls. Plasma epinephrine levels were also elevated in adult rats exposed to DEX in utero. RT-PCR analysis revealed adrenal PNMT mRNA was higher in DEX exposed adult rats. This was associated with increased mRNA levels of transcriptional regulators of the PNMT gene: Egr-1, AP-2, and GR. Western blot analyses showed increased expression of PNMT protein, along with increased Egr-1 and GR in adult rats exposed to DEX in utero. Furthermore, gel mobility shift assays showed increased binding of Egr-1 and GR to DNA. These results suggest that increased PNMT gene expression via altered transcriptional activity is a possible mechanism by which prenatal exposure to elevated levels of GCs may program for hypertension later in life.
authors.affiliation: Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Khurana
authors.affiliation: Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Peltsch
authors.affiliation: Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Grandbois
authors.affiliation: Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Eibl
authors.affiliation: Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Crispo
authors.affiliation: Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Ansell
authors.affiliation: Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada Medical Sciences DivisionNorthern Ontario School of Medicine, Sudbury, Ontario, CanadaDepartments of BiologyChemistry and BiochemistryBiomolecular Sciences ProgramLaurentian University, Sudbury, Ontario, Canada tc.tai@nosm.ca.
authors.forename: T C
authors.initials: TC
authors.lastname: Tai
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects*; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D005938:Glucocorticoids; D010625:Phenylethanolamine N-Methyltransferase
keywords: Wistar-Kyoto rat; adrenal; fetal programming; glucocorticoids; hypertension; phenylethanolamine N-methyltransferase