Characterization of human adrenal steroidogenesis during fetal development
Open accessAbstract
CONTEXT: The endocrine function of human fetal adrenals (HFAs) is activated already during first trimester, but adrenal steroidogenesis during fetal life is not well characterized. OBJECTIVE: This study aimed to investigate HFA steroidogenesis by analyzing adrenal glands from first and second trimesters. DESIGN AND SETTING: Male and female HFA from gestational weeks (GWs) 8 to 19 were examined, including a total of 101 samples from 83 fetuses. MAIN OUTCOME MEASURE(S): Expression level of steroidogenic genes and protein expression/localization were determined by quantitative PCR and immunohistochemistry, respectively, and intra-adrenal steroid levels were quantified by LC-MS/MS. RESULTS: Transcriptional levels of StAR, CYP11A1, CYP17A1, CYP21A2, CYP11B1/2, and SULT2A1 were significantly higher in second trimester compared to first trimester (P < 0.05), whereas expression levels of 3β-HSD2 and ARK1C3 were unaltered between GWs 8 and 19. All investigated steroidogenic proteins were expressed in a distinct pattern throughout the investigated period, with most enzymes expressed primarily in the fetal zone, except 3β-HSD1/2, which was expressed mainly in the definitive zone. Abundant steroidogenic enzyme expression was reflected in overall high intra-adrenal tissue concentrations of mineralocorticoids, glucocorticoids, and androgens; cortisol was the most abundant (1071 to 2723 ng/g tissue), and testosterone levels were the lowest (2 to 14 ng/g tissue). CONCLUSIONS: The expression profiles of HFA steroidogenic enzymes are distinct from first to second trimester, with no major differences between male and female samples. Intra-adrenal steroid hormone concentrations confirm that cortisol is produced throughout first and second trimesters, suggesting continued regulation of the hypothalamus-pituitary-adrenal axis during this entire period.
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The secreted steroid hormone profiles of androgens, glucocorticoids and steroidogenic intermediates from the cultured human fetal adrenal tissue are in accordance with the intra-adrenal metabolites previously measured in un-cultured 1st trimester human fetal adrenal samples.
“The secreted steroid hormone profiles of androgens, glucocorticoids and steroidogenic intermediates from the cultured tissue is in accordance with the intra-adrenal metabolites previously measured in un-cultured 1 st trimester HFA samples (5).”
From Establishment of a novel human fetal adrenal culture model that supports de novo and manipulated steroidogenesis (2021) · cites this paper as [5]
Intra-adrenal concentrations of corticosteroids are similar between 1st and 2nd trimester HFA tissues.
“similar intra-adrenal concentrations of corticosteroids (5)”
From Establishment of a novel human fetal adrenal culture model that supports de novo and manipulated steroidogenesis (2021) · cites this paper as [5]
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- Authors
- Melau, C., Nielsen, J. E., Frederiksen, H., Kilcoyne, K., Perlman, S., Lundvall, L., Langhoff Thuesen, L., Juul Hare, K., Andersson, A.-M., Mitchell, R. T., Juul, A., & Jørgensen, A.
- Affiliations
- University of Copenhagen (DK)
- MRC Centre for Reproductive Health (GB)
- Rigshospitalet (DK)
- Department of Obstetrics and Gynaecology, Hvidovre University Hospital, Hvidovre, Denmark
- Corresponding author
- Jørgensen, Anne
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2018-12-21
- Volume
- 104
- Issue
- 5
- Pages
- 1802-1812
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC6456011
- OpenAlex
- W2906132852
- Cited by
- 47
- References
- 26
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 1 · 2023: 5 · 2022: 11 · 2021: 8 · 2020: 8 · 2019: 1 · 2018: 1
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health
- Lundbeckfonden (R249-2017-1484)
- Wellcome Trust (098522)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- fetal adrenal gland, adrenal steroidogenesis, fetal development, steroidogenic enzymes, first trimester, second trimester, cortisol, mineralocorticoids, glucocorticoids, androgens, steroidogenic gene expression, hypothalamic-pituitary-adrenal axis
- MeSH terms
- Adrenal Glands, Aromatase, Female, Gestational Age, Humans, Male, Pregnancy, Pregnancy Trimester, Second, Gonadal Steroid Hormones, 17-Hydroxysteroid Dehydrogenases, Fetal Development
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