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In vitro methods to assess 11ß-hydroxysteroid dehydrogenase type 2 activity.
Kley, Manuel; Moser, Seraina O; Winter, Denise V; Odermatt, Alex.
Afiliación
  • Kley M; Division 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.
  • Moser SO; Division 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.
  • Winter DV; Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
  • Odermatt A; Division 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. Electronic address: alex.odermatt@unibas.ch.
Methods Enzymol ; 689: 167-200, 2023.
Article en En | MEDLINE | ID: mdl-37802570
11ß-Hydroxysteroid dehydrogenase type 2 (11ß-HSD2) converts active 11ß-hydroxyglucocorticoids to their inactive 11-keto forms, fine-tuning the activation of mineralocorticoid and glucocorticoid receptors. 11ß-HSD2 is expressed in mineralocorticoid target tissues such as renal distal tubules and cortical collecting ducts, and distal colon, but also in placenta where it acts as a barrier to reduce the amount of maternal glucocorticoids that reach the fetus. Disruption of 11ß-HSD2 activity by genetic defects or inhibitors causes the syndrome of apparent mineralocorticoid excess (AME), characterized by hypernatremia, hypokalemia and hypertension. Secondary hypertension due to 11ß-HSD2 inhibition has been observed upon consumption of excessive amounts of licorice and in patients treated with the azole fungicides posaconazole and itraconazole. Furthermore, inhibition of 11ß-HSD2 during pregnancy with elevated exposure of the fetus to cortisol can cause neurological complications with a lower intelligence quotient, higher odds of attention deficit and hyperactivity disorder as well as metabolic reprogramming with an increased risk of cardio-metabolic disease in adulthood. This chapter describes in vitro methods for the determination of 11ß-HSD2 activity that can be applied to identify inhibitors that may cause secondary hypertension and characterize the enzyme's activity in disease models. The included decision tree and the list of methods with their advantages and disadvantages aim to enable the reader to select and apply an in vitro method suitable for the scientific question and the equipment available in the respective laboratory.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Exceso Aparente de Mineralocorticoides / Hipertensión Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Methods Enzymol Año: 2023 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Exceso Aparente de Mineralocorticoides / Hipertensión Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Methods Enzymol Año: 2023 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos