The University of Southampton
University of Southampton Institutional Repository

The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11ß-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero

Record type: Article

Potential mechanisms underlying prenatal programming of hypertension in adult life were investigated using a rat model in which maternal protein intake was restricted to 9% vs. 18% casein (control) during pregnancy. Maternal low protein (MLP) offspring exhibit glucocorticoid-dependent raised systolic blood pressure throughout life (20–30 mm Hg above the control).
To determine the molecular mechanisms underlying the role of alterations in glucocorticoid hormone action in the prenatal programming of hypertension in MLP offspring, tissues were analyzed for expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11ßHSD1, 11ßHSD2, and corticosteroid-responsive Na/K-adenosine triphosphatase 1 and ß1. GR protein (95 kDa) and messenger RNA (mRNA) expression in kidney, liver, lung, and brain was more than 2-fold greater in MLP vs. control offspring during fetal and neonatal life and was more than 3-fold higher during subsequent juvenile and adult life (P < 0.01). This was associated with increased levels of Na/K-adenosine triphosphatase 1- and ß1-subunit mRNA expression. Levels of MR gene expression remained unchanged. Exposure to the MLP diet also resulted in markedly reduced levels of 11ßHSD2 expression in the MLP placenta on days 14 and 20 of gestation (P < 0.001), underpinning similar effects on 11ßHSD2 enzyme activity that we reported previously. Levels were also markedly reduced in the kidney and adrenal of MLP offspring during fetal and postnatal life (P < 0.001). This programmed decline in 11ßHSD2 probably contributes to marked increases in glucocorticoid hormone action in these tissues and potentiates both GR- and MR-mediated induction of raised blood pressure. In contrast, levels of 11ßHSD1 mRNA expression in offspring central and peripheral tissues remained unchanged.
In conclusion, we have demonstrated that mild protein restriction during pregnancy programs tissue-specific increases in glucocorticoid hormone action that are mediated by persistently elevated expression of GR and decreased expression of 11ßHSD2 during adult life. As glucocorticoids are potent regulators not only of fetal growth but also of blood pressure, our data suggest important potential molecular mechanisms contributing to the prenatal programming of hypertension by maternal undernutrition in the rat.

Full text not available from this repository.

Citation

Bertram, C.E., Trowern, A.R., Copin, N., Jackson, A.A. and Whorwood, C.B. (2001) The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11ß-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero Endocrinology, 142, (7), pp. 2841-2853.

More information

Published date: 2001

Identifiers

Local EPrints ID: 25250
URI: http://eprints.soton.ac.uk/id/eprint/25250
ISSN: 0013-7227
PURE UUID: 4f284151-ec67-408e-b406-6ec9663cf180

Catalogue record

Date deposited: 10 Apr 2006
Last modified: 17 Jul 2017 16:11

Export record

Contributors

Author: C.E. Bertram
Author: A.R. Trowern
Author: N. Copin
Author: A.A. Jackson
Author: C.B. Whorwood

University divisions


Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×