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Glucocorticoid receptor polymorphism in genetic hypertension
C J Kenyon1, M Panarelli, L Zagato
1Molecular Medicine Centre, Western General Hospital, Edinburgh, UK.
Journal of Molecular Endocrinology
|September 2, 1998
Summary
Glucocorticoid receptor (GR) gene variations in Milan hypertensive rats (MHS) are linked to altered receptor binding affinity and adrenal function. This genetic polymorphism may influence blood pressure regulation in this hypertensive rat model.
Area of Science:
- Endocrinology
- Genetics
- Nephrology
Background:
- Milan hypertensive rats (MHS) exhibit renal and adrenocortical abnormalities, with the role of the latter needing further investigation.
- Previous studies noted elevated plasma corticosterone and adrenocortical hypertrophy in MHS rats.
Purpose of the Study:
- To investigate glucocorticoid receptor (GR) binding characteristics in MHS and Milan normotensive control (MNS) rats.
- To determine the genetic sequence of the GR gene in MHS and MNS rats and analyze its association with physiological traits.
Main Methods:
- Assessed GR binding affinity for dexamethasone, aldosterone, and corticosterone in liver cytosol from MHS and MNS rats.
- Sequenced the GR gene in both rat strains and identified polymorphisms.
- Conducted cosegregation studies using F2 hybrids of MHS x MNS rats.
Main Results:
- MHS rats exhibited lower affinity binding of glucocorticoids compared to MNS rats.
- A polymorphic microsatellite region in exon 2 of the MHS GR gene was identified.
- The MHS GR genotype correlated with hypercalciuria and lower blood pressure in female rats, and lower body weight in males.
Conclusions:
- GR gene polymorphism in MHS rats may account for differences in adrenocortical function compared to MNS rats.
- This polymorphism could potentially reduce the blood pressure difference between the two rat strains.