11 beta-Hydroxysteroid dehydrogenase activity and corticosteroid hormone action

Area of Science:

• Endocrinology
• Molecular Biology
• Cell Biology

Background:

• 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) normally protects the mineralocorticoid receptor (MR) from glucocorticoids.
• Widespread 11 beta-OHSD expression in rats suggests a role in regulating glucocorticoid receptor (GR) access.

Purpose of the Study:

• To investigate the role of 11 beta-OHSD in modulating corticosteroid hormone action in rat pituitary GH3 and renal NRK-52E cells.
• To determine how 11 beta-OHSD influences prolactin gene transcription and Na-K ATPase subunit gene expression.

Main Methods:

• Utilized rat pituitary GH3 and renal epithelial NRK-52E cell lines.
• Analyzed 11 beta-OHSD activity, mRNA, and protein levels via Northern/Western blots.
• Assessed the effects of corticosterone, glycyrrhetinic acid (11 beta-OHSD inhibitor), and specific receptor agonists/antagonists on gene expression.

Main Results:

• In GH3 cells, inhibiting 11 beta-OHSD enabled corticosterone to suppress prolactin mRNA, mimicking GR agonist effects.
• In NRK-52E cells, combined corticosterone and 11 beta-OHSD inhibition significantly increased Na-K ATPase subunit mRNA, indicating MR activation.
• Both effects were reversible with specific GR and MR antagonists, respectively.

Conclusions:

• 11 beta-OHSD plays a significant role in regulating corticosteroid hormone action in rat pituitary and kidney cells.
• The enzyme modulates ligand access to both the glucocorticoid receptor and the mineralocorticoid receptor.
• These findings highlight the importance of 11 beta-OHSD in intracellular corticosteroid signaling pathways.