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11 beta-Hydroxysteroid dehydrogenase in the rat adrenal
M Shimojo1, C B Whorwood, P M Stewart
1Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, UK.
Journal of Molecular Endocrinology
|October 1, 1996
Summary
The rat adrenal gland expresses both 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) isoforms, 11 beta-HSD1 and 11 beta-HSD2. 11 beta-HSD1 is localized to the cortico-medullary junction, suggesting a role in regulating adrenaline biosynthesis.
Area of Science:
- Endocrinology
- Molecular Biology
- Biochemistry
Background:
- 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) interconverts active cortisol/corticosterone to inactive cortisone/11-dehydrocorticosterone.
- Two isoforms, 11 beta-HSD1 (low-affinity, NADP(H)-dependent oxoreductase) and 11 beta-HSD2 (high-affinity, NAD-dependent dehydrogenase), have been characterized.
- These isoforms modulate mineralocorticoid and glucocorticoid receptor access and activity.
Purpose of the Study:
- To analyze the expression of 11 beta-HSD1 and 11 beta-HSD2 isoforms in the rat adrenal gland (cortex and medulla).
- To investigate the role of these isoforms in glucocorticoid-regulated enzymes involved in catecholamine biosynthesis in adrenal medullary chromaffin cells.
Main Methods:
- Northern blot analysis to detect mRNA expression of 11 beta-HSD1 and 11 beta-HSD2.
- Measurement of 11 beta-dehydrogenase and 11-oxoreductase activities in adrenal homogenates.
- In situ hybridization to localize mRNA expression within the adrenal gland.
- Administration of glycyrrhizic acid, an 11 beta-HSD inhibitor, to assess in vivo effects on enzyme activity and mRNA levels.
Main Results:
- Both 11 beta-HSD1 and 11 beta-HSD2 mRNA were detected in the whole rat adrenal gland.
- 11 beta-HSD1 mRNA was predominantly localized to the corticomedullary junction, while 11 beta-HSD2 mRNA was more abundant in the cortex.
- Glycyrrhizic acid inhibited both 11 beta-HSD activities and reduced 11 beta-HSD1 mRNA levels, but not 11 beta-HSD2 mRNA.
- Inhibition of 11 beta-HSD led to reduced mRNA levels of the glucocorticoid-dependent enzyme phenylethanolamine N-methyltransferase, but not the glucocorticoid-independent enzyme tyrosine hydroxylase.
Conclusions:
- The rat adrenal gland expresses both 11 beta-HSD1 and 11 beta-HSD2 isoforms.
- 11 beta-HSD1's localization suggests a role in regulating corticosterone supply to medullary chromaffin cells.
- 11 beta-HSD1 likely plays a significant role in adrenocorticosteroid regulation of adrenaline biosynthesis.