Insulin Regulates Adrenal Steroidogenesis by Stabilizing SF-1 Activity
Open accessAbstract
Development of metabolic syndrome is associated with hyperactivity of the HPA axis characterized by elevated levels of circulating adrenal hormones including cortisol and aldosterone. However, the molecular mechanism leading to the dysregulation of the HPA axis is not well elucidated. In this study, we found that insulin regulates adrenal steroidogenesis by increasing the expression and activity of steroidogenic factor 1 (SF-1) both in vitro and in vivo and this insulin effect was partly through inhibition of FoxO1. Specifically, insulin increased the protein and RNA levels of SF-1 and steroidogenic target genes. Further, adrenal SF-1 expression was significantly increased by hyperactivation of insulin signaling in mice. Together with the elevated SF-1 expression in adrenal glands, hyperactivation of insulin signaling led to increased aldosterone and corticosterone levels. On the other hand, suppressing the insulin signaling using streptozotocin markedly reduced the expression of adrenal SF-1 in mice. In addition, overexpression of FoxO1 significantly suppressed SF-1 and its steroidogenic target genes implying that the positive effect of insulin on SF-1 activity might be through suppression of FoxO1 in the adrenal gland. Taken together, these results indicate that insulin regulates adrenal steroidogenesis through coordinated control of SF-1 and FoxO1.
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Insulin upregulates adrenal androgen synthesis by affecting steroidogenic factor 1 (SF-1).
“Insulin also upregulates adrenal androgen synthesis by affecting steroidogenic factor 1 (SF-1), which is a transcriptional factor playing an important role in steroid hormone synthesis by regulating the transcription of steroidogenic genes, including StAR, Cyp11a1, Cyp17, Cyp11b1, Cyp11b2, and 3β-Hsd [65].”
From The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome (2022) · cites this paper as [65]
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Bednarz, K., Kowalczyk, K., Cwynar, M., Czapla, D., Czarkowski, W., Kmita, D., Nowak, A., & Madej, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084334 · Cited by 148 · see citing works
- Authors
- Kinyua, A. W., Doan, K. V., Yang, D. J., Huynh, M. K. Q., Choi, Y.-H., Shin, D. M., & Kim, K. W.
- Affiliations
- Yonsei University (KR)
- Corresponding author
- Kim, Ki Woo
- Venue
- Scientific Reports
- Published
- 2018-03-22
- Volume
- 8
- Issue
- 1
- Pages
- 5025-5025
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5864882
- OpenAlex
- W2805180610
- Cited by
- 37
- References
- 39
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 8 · 2023: 8 · 2022: 7 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 1
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- Korean Society for the Study of Obesity
- National Research Foundation (NRF-2016R1C1B3012748)
- Korea Health Industry Development Institute (HI17C0745)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- 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
- insulin signaling, adrenal steroidogenesis, steroidogenic factor 1, FOXO1, hypothalamic-pituitary-adrenal axis, metabolic syndrome, aldosterone, corticosterone, streptozotocin, adrenal gland, protein stabilization
- MeSH terms
- Forkhead Box Protein O1, Adrenal Cortex, Aldosterone, Animals, Corticosterone, Diabetes Mellitus, Experimental, Female, Humans, Hypothalamo-Hypophyseal System, Insulin, Male, Mice, Inbred C57BL, Phosphorylation, Pituitary-Adrenal System, Streptozocin, RNA, Small Interfering, Cell Line, Tumor, Mice, Biosynthetic Pathways, Steroidogenic Factor 1, Gene Knockdown Techniques, HEK293 Cells, Diet, High-Fat
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