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In vitro methods to assess 11β-hydroxysteroid dehydrogenase type 2 activity
Manuel Kley1, Seraina O Moser1, Denise V Winter2
1Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; Swiss Centre for Applied Human Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) protects against excess mineralocorticoid and glucocorticoid receptor activation. This summary details in vitro methods to assess 11β-HSD2 activity and identify potential inhibitors.
Area of Science:
- Biochemistry
- Endocrinology
- Pharmacology
Background:
- 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) inactivates active glucocorticoids, regulating mineralocorticoid and glucocorticoid receptor signaling.
- 11β-HSD2 is crucial in mineralocorticoid target tissues and the placenta, preventing fetal exposure to maternal glucocorticoids.
- Defects or inhibition of 11β-HSD2 lead to apparent mineralocorticoid excess (AME) and secondary hypertension.
Purpose of the Study:
- To describe in vitro methods for determining 11β-HSD2 activity.
- To facilitate the identification of compounds that inhibit 11β-HSD2, potentially causing secondary hypertension.
- To aid in characterizing 11β-HSD2 activity in various disease models.
Main Methods:
- Review and description of various in vitro assays for measuring 11β-HSD2 enzymatic activity.
- Inclusion of a decision tree to guide method selection based on research questions and available laboratory equipment.
- Comparative analysis of advantages and disadvantages of different methodologies.
Main Results:
- Provides a comprehensive overview of available in vitro methods for 11β-HSD2 activity assessment.
- Highlights the link between 11β-HSD2 inhibition and conditions like AME, licorice-induced hypertension, and azole fungicide side effects.
- Emphasizes the potential for fetal neurological and metabolic complications due to in utero cortisol excess from 11β-HSD2 inhibition.
Conclusions:
- Standardized in vitro methods are essential for studying 11β-HSD2 function and identifying inhibitors.
- Accurate assessment of 11β-HSD2 activity is critical for understanding hypertension and developmental risks.
- The provided guidelines assist researchers in selecting appropriate methods for their specific investigations.
