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Cited by 135Growth Hormone and Insulin-like Growth FactorsAdrenal Hormones and DisordersPancreatic function and diabetes

Mitogenic action, regulation, and localization of insulin-like growth factors in the human fetal adrenal gland.

Mesiano, S, Mellon, S H, Jaffe, R B·1993·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem.76.4.8473412
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Abstract

Polypeptide growth factors may play an important role in the regulation of human fetal adrenal cortical growth by mediating the tropic actions of ACTH. The abundance of mRNA encoding insulin-like growth factor-II (IGF-II) is high in the human fetal adrenal gland and is stimulated by ACTH in cultured fetal adrenal cortical cells. Therefore, we studied the mitogenic action, regulation, and localization of IGF-II and a closely related peptide, IGF-I, in primary cultures of human fetal adrenal cortical cells and whole human fetal adrenal glands. Recombinant human IGF-I and IGF-II stimulated proliferation of fetal adrenal cortical cells in a dose-dependent fashion (1-1000 ng/mL; 0.133-133 nM). At 1000 ng/mL (133 nM), both peptides increased cell number 1.8- to 2-fold. Combinations of IGF-I or -II (100 ng/mL; 13.3 nM) with basic fibroblast growth factor (bFGF; 0.1 ng/mL; 6 pM) or epidermal growth factor (EGF; 1.0 ng/mL; 0.17 nM) had a greater effect on proliferation than bFGF, EGF, or either of the IGFs alone, suggesting an additive interaction. IGF-II mRNA was detected in cultured adrenal cortical cells by in situ hybridization analysis, and its abundance was stimulated by ACTH. In contrast, IGF-I mRNA was not detected in cultured fetal zone cells and was not regulated by ACTH. In whole human fetal adrenal glands, IGF-II mRNA was detected in the definitive and fetal zones and in the capsule, whereas IGF-I mRNA was detected only in the capsule and not in the two cortical zones. Using Northern blot analysis, we found that mRNA encoding IGF-II was present in high abundance in fetal adrenal glands (16-22 weeks) and barely detectable in adult adrenals, whereas mRNA encoding IGF-I was present in very low abundance in the fetal adrenal, but was high in adult human adrenals. As IGF-II expression is high in the human fetal adrenal cortex and is regulated by ACTH, we propose that it is the dominant of the two IGFs regulating human fetal adrenal growth. The cooperative mitogenic effect of IGF-II with bFGF and EGF and the regulation of its expression by ACTH support the hypothesis that IGF-II may act as a mediator, in concert with bFGF and possibly EGF, of the tropic action of ACTH in regulating the rapid growth of the human fetal adrenal cortex during midgestation.

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  • ACTH promotes adrenal growth primarily by stimulating cAMP production, which promotes synthesis of IGF-II, basic fibroblast growth factor, and epidermal growth factor; together these growth factors stimulate adrenal cellular hypertrophy and hyperplasia, determining the amount of steroidogenic tissue.

    “This growth occurs primarily by ACTH stimulating the production of cAMP, which in turn promotes the synthesis of IGF-II (54, 55), basic fibroblast growth factor (56), and epidermal growth factor (57). Together, these growth factors stimulate adrenal cellular hypertrophy and hyperplasia, determining the amount of steroidogenic tissue.”

    From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [55]

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Authors
Mesiano, S., Mellon, S. H., & Jaffe, R. B.
Affiliations
University of California, San Francisco (US)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
1993-04
Volume
76
Issue
4
Pages
968-976
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem.76.4.8473412
OpenAlex
W2048035500
Cited by
135
References
52
Citations by year
2025: 2 · 2023: 4 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 6 · 2017: 1 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 2 · 2012: 4
FWCI
3.22
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 22013, HD-08478)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
insulin-like growth factor II, insulin-like growth factor I, fetal adrenal gland, mitogenic activity, ACTH regulation, basic fibroblast growth factor, epidermal growth factor, cell proliferation, IGF-II mRNA expression, human fetus, placenta, placental growth factor
MeSH terms
Adrenal Glands, Cells, Cultured, Fetus, Humans, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Mitogens, Recombinant Proteins, RNA, Messenger, Tissue Distribution, Blotting, Northern, In Situ Hybridization

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