Development and function of the human fetal adrenal cortex: a key component in the feto-placental unit
Open accessAbstract
Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex.
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The Δ5 steroids pregnenolone, 17α-hydroxypregnenolone, and DHEA probably come from the fetal adrenal gland.
“and these steroids probably come from the fetal adrenal gland [20,21].”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [20]
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Cumberland, A. L., Hirst, J. J., Badoer, E., Wudy, S. A., Greaves, R. F., Zacharin, M., & Walker, D. W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094296 · Cited by 26 · see citing works
- Authors
- Ishimoto, H., & Jaffe, R. B.
- Affiliations
- Tokai University (JP)
- University of California, San Francisco (US)
- ORCID
- Ishimoto, Hitoshi
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2010-11-04
- Volume
- 32
- Issue
- 3
- Pages
- 317-355
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- PMC
- PMC3365797
- OpenAlex
- W1969689856
- Cited by
- 379
- References
- 424
- Citations by year
- 2026: 16 · 2025: 30 · 2024: 26 · 2023: 27 · 2022: 29 · 2021: 31 · 2020: 26 · 2019: 32 · 2018: 30 · 2017: 30 · 2016: 24 · 2015: 17 · 2014: 19 · 2013: 19 · 2012: 15
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrine Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32HD008478, HD-08478)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- fetal adrenal cortex, adrenal development, steroidogenesis, cortisol, dehydroepiandrosterone, placental estrogens, fetoplacental unit, fetal development, ACTH, corticotropin-releasing factor, adrenal growth, apoptosis, gene expression profiling, laser capture microdissection, pregnancy, childbirth
- MeSH terms
- Adrenal Cortex, Female, Humans, Placenta, Pregnancy, Neovascularization, Physiologic, Parturition, Fetal Development
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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.
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