Nuclear Receptors Nor1 and NGFI-B/Nur77 Play Similar, Albeit Distinct, Roles in the Hypothalamo-Pituitary-Adrenal Axis1
Abstract
Studies in Nur77-deficient mice have shown that the basal regulation of hypothalamic and pituitary functions as well as the adrenocortical steroidogenesis in these animals is normal. This indicates that Nur77-related orphan receptors may substitute Nur77 functions in the hypothalamo-pituitary-adrenal axis by a compensatory mechanism. Nor1 is the most recently cloned member of the NGFI-B/Nur77 subfamily, and its properties are still largely unknown. We demonstrate here that Nor1 is expressed in the pituitary gland and adrenal cortex, and that ACTH and angiotensin II (AngII) treatment of adrenal fasciculata cells induces Nor1 expression. Time-course analysis with both hormones on steroidogenic capacity and the specific gene expression in adrenal cells strongly suggest that Nor1 is an intermediate in the long-term consequences of ACTH or AngII treatment. The Nor1 and NGFI-B/Nur77 amino acid sequence homology and the analysis of the trans-activation properties of Nor1 show that the overall structural and functional organization of the two proteins is similar. As observed with NGFI-B/Nur77, Nor1 activates the expression of genes encoding steroidogenic enzymes as P450c21, through its interaction with NGFI-B response element promoter sequences. In contrast, binding experiments of Nor1 with the palindromic NurRE sequence suggest that Nor1 is not an efficient substitute for the NGFI-B/Nur77 activation of the POMC gene expression in pituitary glands. All these results indicate that Nor1 and NGFI-B/Nur77 may play similar albeit distinct roles in the hypothalamo-pituitary-adrenal axis. Further experiments also show that the mechanisms responsible for the transcriptional regulation of Nor1 in adrenal cells appear to depend on the protein kinase A and protein kinase C cascades.
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Additional relevant transcription factors include nerve growth factor induced-B and Nur-related factor 1, which may overlap in their functions.
“Additional relevant transcription factors include nerve growth factor induced-B (NGFI-B, Nur77, NR4A1)(169,184), and Nur-related factor 1 (NURR1) (NR4A2); they may overlap in their functions (185).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [184]
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- Authors
- Fernandez, P. M., Brunel, F., Jimenez, M. A., Saez, J. M., Cereghini, S., & Zakin, M. M.
- Affiliations
- Institut Pasteur (FR)
- Inserm (FR)
- Hôpital Necker-Enfants Malades (FR)
- Corresponding author
- Zakin, Mario M.
- ORCID
- Cereghini, Silvia
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2000-07
- Volume
- 141
- Issue
- 7
- Pages
- 2392-2400
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2069436500
- Cited by
- 85
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 1 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 4 · 2012: 2
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- NOR-1, nuclear receptors, hypothalamic-pituitary-adrenal axis, ACTH, angiotensin II, adrenal fasciculata cells, steroidogenesis, P450c21, proopiomelanocortin, transcriptional activation, protein kinase A, protein kinase C
- MeSH terms
- Adrenal Cortex, Adrenal Glands, Adrenocorticotropic Hormone, Angiotensin II, Animals, Cell Nucleus, Cytochrome P-450 Enzyme System, DNA-Binding Proteins, Hypothalamo-Hypophyseal System, Nerve Tissue Proteins, Nuclear Proteins, Pituitary Gland, Pituitary-Adrenal System, Pro-Opiomelanocortin, Promoter Regions, Genetic, Receptors, Steroid, Receptors, Thyroid Hormone, RNA, Messenger, Steroid 21-Hydroxylase, Transcription Factors, Second Messenger Systems, Transcriptional Activation, Gene Expression, Genes, Reporter, Receptors, Cytoplasmic and Nuclear, COS Cells, Nuclear Receptor Subfamily 4, Group A, Member 1
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