Angiotensin II Triggers Expression of the Adrenal Gland Zona Glomerulosa-Specific 3β-Hydroxysteroid Dehydrogenase Isoenzyme through De Novo Protein Synthesis of the Orphan Nuclear Receptors NGFIB and NURR1
| Autor: | Fumiyoshi Yamazaki, Takumi Ota, Hitoshi Okamura, Masao Doi, Yuuki Nakagawa, Hida Hayashi, Kazuki Okada, Daisuke Yarimizu, Iori Murai, Sumihiro Kunisue |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Gene isoform endocrine system medicine.medical_specialty Transcription Genetic Steroid Isomerases Biology Response Elements Cell Line Mice chemistry.chemical_compound Multienzyme Complexes Internal medicine Adrenal Glands Nuclear Receptor Subfamily 4 Group A Member 2 Nuclear Receptor Subfamily 4 Group A Member 1 medicine Animals Humans Receptor Molecular Biology Binding Sites Aldosterone Progesterone Reductase Adrenal gland Angiotensin II Articles Cell Biology Isoenzymes Mice Inbred C57BL medicine.anatomical_structure Endocrinology chemistry Zona glomerulosa Enzyme Induction Protein Biosynthesis HSD3B1 HSD3B2 hormones hormone substitutes and hormone antagonists Protein Binding |
| Zdroj: | Molecular and Cellular Biology. 34:3880-3894 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.00852-14 |
| Popis: | The 3β-hydroxysteroid dehydrogenase (3β-HSD) is an enzyme crucial for steroid synthesis. Two different 3β-HSD isoforms exist in humans. Classically, HSD3B2 was considered the principal isoform present in the adrenal. However, we recently showed that the alternative isoform, HSD3B1, is expressed specifically within the adrenal zona glomerulosa (ZG), where aldosterone is produced, raising the question of why this isozyme needs to be expressed in this cell type. Here we show that in both human and mouse, expression of the ZG isoform 3β-HSD is rapidly induced upon angiotensin II (AngII) stimulation. AngII is the key peptide hormone regulating the capacity of aldosterone synthesis. Using the human adrenocortical H295R cells as a model system, we show that the ZG isoform HSD3B1 differs from HSD3B2 in the ability to respond to AngII. Mechanistically, the induction of HSD3B1 involves de novo protein synthesis of the nuclear orphan receptors NGFIB and NURR1. The HSD3B1 promoter contains a functional NGFIB/NURR1-responsive element to which these proteins bind in response to AngII. Knockdown of these proteins and overexpression of a dominant negative NGFIB both reduce the AngII responsiveness of HSD3B1. Thus, the AngII-NGFIB/NURR1 pathway controls HSD3B1. Our work reveals HSD3B1 as a new regulatory target of AngII. |
| Databáze: | OpenAIRE |
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