The periphery of the human fetal adrenal gland is a site of angiogenesis: zonal differential expression and regulation of angiogenic factors
Open accessAbstract
CONTEXT: Although the inner fetal zone (FZ) of the mid-gestation human fetal adrenal (HFA) produces dehydroepiandrosterone sulfate, the function of the outer definitive zone (DZ) remains less clear. We have proposed that the DZ phenotype is that of a pool of progenitor cells, many of which are mitotically active. Recently, we studied HFA expression of a family of vascular endothelial cell-specific angiogenic factors, the angiopoietins (Angs), and demonstrated that Ang2 was localized predominantly in the periphery of the gland. Ang1 stabilizes, whereas Ang2 destabilizes, vessels, increasing responsiveness to angiogenic stimuli such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF)-2. OBJECTIVE: Our objective was to test the hypothesis that the periphery of the HFA is a site of angiogenesis. DESIGN: Studies were conducted involving RNA, frozen sections, and primary cell cultures from midgestation HFAs. MAIN OUTCOME MEASURES: Immunofluorescence, laser capture microdissection, and real-time quantitative RT-PCR were used. RESULTS: Double immunostaining demonstrated that proliferating endothelial cells were limited to the DZ and DZ/FZ border. Ang2 mRNA was primarily expressed in the DZ, whereas Ang1 mRNA was primarily in the FZ. VEGF-A and FGF-2 mRNA levels were higher in the DZ. FGF-2 (10 ng/ml) induced Ang2 mRNA by 4-fold in both zones of cells (P < 0.01, at 24 h), but not Ang1 or VEGF-A mRNA. CONCLUSION: Data suggest that angiogenesis occurs at the periphery of the HFA. The DZ-predominant expression of Ang2 may be explained, in part, by the parallel pattern of FGF-2 expression.
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The enlarged fetal zone (FZ) in ACTH stimulated tissue found in the present study after both 7 and 14 days treatment could also explain the tendency towards a decreased number of proliferating cells, since definitive zone (DZ) cells are known to have a higher proliferation rate than FZ cells.
“The enlarged FZ in ACTH stimulated tissue found in the present study after both 7and 14-days treatment could also explain the tendency towards a decreased number of proliferating cells since DZ cells are known to have a higher proliferation rate than FZ cells (25).”
From Establishment of a novel human fetal adrenal culture model that supports de novo and manipulated steroidogenesis (2021) · cites this paper as [25]
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- Authors
- Ishimoto, H., Minegishi, K., Higuchi, T., Furuya, M., Asai, S., Kim, S. H., Tanaka, M., Yoshimura, Y., & Jaffe, R. B.
- Affiliations
- University of California, San Francisco (US)
- Keio University (JP)
- Corresponding author
- Jaffe, Robert B.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2008-06-01
- Volume
- 93
- Issue
- 6
- Pages
- 2402-2408
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2435642
- OpenAlex
- W1982182913
- Cited by
- 18
- References
- 45
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 1 · 2015: 1 · 2012: 2
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- University of California, San Francisco
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh
- Japan Society for the Promotion of Science (94143, 18659313, 19591288)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32HD008478, HD-08478)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- angiogenesis, angiopoietin-2, angiopoietin-1, VEGF-A, fibroblast growth factor 2, endothelial cell proliferation, fetal adrenal development
- MeSH terms
- Adrenal Glands, Angiotensin I, Angiotensin II, Cell Differentiation, Cells, Cultured, Female, Fetus, Gestational Age, Humans, Models, Biological, Pregnancy, RNA, Messenger, Tissue Distribution, Fibroblast Growth Factor 2, Gene Expression Regulation, Developmental, Neovascularization, Physiologic, Vascular Endothelial Growth Factor A, Angiogenic Proteins, Endothelial Cells
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