Modulation of steroidogenic enzymes by orphan nuclear transcriptional regulation may control diverse production of cortisol and androgens in the human adrenal
Open accessAbstract
The capacity of the adrenal to produce cortisol is controlled in part by 21-hydroxylase (CYP21) and the production of androgens by 17-hydroxylase/17-20-lyase (CYP17), in response to secretagogues including ACTH, angiotensin-II (A-II) and insulin. In this study we examined the capacity of human adrenocortical cells to produce cortisol and androgens in response to these secretagogues and their ability to regulate the expression of CYP21 and CYP17. In H-295 cells, forskolin and A-II were found to stimulate production of cortisol relative to androstenedione and a similar pattern of steroid production was noted in primary human adrenocortical cells. Both mRNA and protein expression of CYP21 was upregulated with forskolin and A-II alone and in combination, as detected by Northern and Western blotting. Whereas expression of CYP17 mRNA and protein was up regulated in the presence of forskolin and forskolin in combination with insulin. The ability of steroidogenic factor-1 (SF-1) and nur77 to regulate transcription of these enzymes was examined. Forskolin, A-II and insulin increased the protein expression of SF-1. Increased binding of SF-1 to its response element in the presence of forskolin, A-II and insulin was observed. Nur77 was expressed primarily in the zona glomerulosa and fasciculata. Increased protein expression of nur77 and the greatest binding of nur77 to its response element was seen when cells were stimulated with A-II in combination with forskolin. These data indicate that nur77 may preferentially regulate steroid enzyme genes relevant to cortisol production and thereby regulate differential cortisol and adrenal androgen production.
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High extracellular potassium levels trigger voltage sensitive calcium channels that increase intracellular calcium levels, and calcium then increases activity of protein kinase C.
“Additionally, high extracellular potassium levels trigger voltage sensitive calcium channels that also increase intracellular calcium levels.Calcium then increases activity of protein kinase C (167).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [167]
The Functional analysis section says angiotensin II was used to activate the protein kinase C pathway, but it does not describe potassium stimulation or calcium-channel activity. Searches for extracellular potassium, voltage-sensitive calcium channels, and calcium activation of protein kinase C found no passage establishing the claimed sequence. (LLM, conf=0.75)
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- Authors
- Kelly, S., McKenna, T., & Young, L.
- Affiliations
- University College Dublin (IE)
- St. Vincent's University Hospital (IE)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2004-05-01
- Volume
- 181
- Issue
- 2
- Pages
- 355-365
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2133293235
- Cited by
- 56
- References
- 40
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 5 · 2012: 5
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Texas Southwestern Medical Center
- Enterprise Ireland
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- steroidogenic enzymes, CYP21, CYP17, cortisol production, adrenal androgens, androstenedione, steroidogenic factor 1, Nur77, orphan nuclear receptor, angiotensin II, forskolin, insulin, ACTH, adrenocortical cells, zona glomerulosa, zona fasciculata, transcriptional regulation
- MeSH terms
- Adrenal Glands, Adrenocorticotropic Hormone, Androgens, Angiotensin II, Cell Line, DNA-Binding Proteins, Enzyme Activation, Colforsin, Gene Expression Regulation, Humans, Hydrocortisone, Immunohistochemistry, Insulin, Receptors, Steroid, RNA, Messenger, Steroid 17-alpha-Hydroxylase, Steroid 21-Hydroxylase, Transcription Factors, Blotting, Northern, Blotting, Western, Receptors, Cytoplasmic and Nuclear, Electrophoretic Mobility Shift Assay, Fushi Tarazu Transcription Factors, Steroidogenic Factor 1, Nuclear Receptor Subfamily 4, Group A, Member 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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