Androgenic potential of human fetal adrenals at the end of the first trimester
Open accessAbstract
The onset of steroidogenesis in human fetal adrenal glands (HFA) during the first trimester is poorly investigated. An unresolved question is the capacity of the HFA to produce potent androgen DHT via conventional and/or the backdoor pathway(s) at the end of first trimester, when androgen-responsive organs are developed. Our aim was to explore steroidogenesis and the expression of steroidogenic enzymes and transcription factors in HFA at gestational weeks (GW) 9–12 with focus on their androgenic potential. Steroids in the HFA were analyzed by gas chromatography/mass spectrometry. The expression of steroidogenic enzymes and transcription factors in the HFA at GW9–12 was investigated by qPCR, automated Western blotting and immunohistochemistry. We demonstrated that during GW9–12 HFA produced steroids of the ∆ 5 , ∆ 4 and the backdoor pathways of the biosynthesis of DHT, though the latter was limited to production of 17α-OH-dihydroprogesterone, androsterone and androstanedione without further conversion to DHT. The only androgens identified in the HFA were testosterone and androsterone, a precursor in the biosynthesis of DHT. We also observed higher levels of CYP17A1 but low expression of 3βHSD2 at GW11–12 in the HFA. Elevated levels of CYP17A1 were associated with an increased expression of SF-1 and GATA-6. Altogether, our data demonstrate that of those steroids analyzed, the only potent androgen directly produced by the HFA at GW9–12 was testosterone. The onset of steroidogenesis in the HFA is a complex process that is regulated by the coordinated action of related transcription factors.
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HSD3B2 activity is likely to be relatively low compared with CYP17A1 in both adrenal and testis, based on transcript levels.
“In addition, HSD3B2 activity is likely to be relatively low compared with CYP17A1 in both tissues, based on transcript levels (this study and [28–30]).”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [28]
In males, tissue androsterone levels are highest in the adrenals, which is consistent with high CYP17A1 transcript levels and with a previous study showing androsterone present in the fetal adrenal at the end of the first trimester.
“In males, tissue androsterone levels are highest in the adrenals, which is consistent with high CYP17A1 transcript levels and with a previous study showing androsterone present in the fetal adrenal at the end of the first trimester [28].”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [28]
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Melau, C., Riis, M. L., Nielsen, J. E., Perlman, S., Lundvall, L., Thuesen, L. L., Hare, K. J., Hammerum, M. S., Mitchell, R. T., Frederiksen, H., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16584678
- Authors
- Savchuk, I., Morvan, M. L., Antignac, J. P., Gemzell-Danielsson, K., Le Bizec, B., Söder, O., & Svechnikov, K.
- Affiliations
- Karolinska University Hospital (SE)
- Université Nantes Angers Le Mans (FR)
- 3Department of Obstetrics and GynecologyKarolinska Institute & University Hospital, Stockholm, Sweden
- 2LUNAM UniversitéÉcole Nationale Vétérinaire, Agroalimentaire et de l’Alimentation, Nantes-Atlantique (Oniris), Laboratoire d’Étude des Résidus et Contaminants dans les Aliments (LABERCA), USC INRA 1329, Nantes, France
- Corresponding author
- Svechnikov, K
- Venue
- Endocrine Connections
- Publisher
- Bioscientifica
- Published
- 2017-08
- Volume
- 6
- Issue
- 6
- Pages
- 348-359
- ISSN
- 2049-3614 (ISSN-L)
- PMC
- PMC5516548
- OpenAlex
- W2623051248
- Cited by
- 20
- References
- 46
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 1
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Endocrine Connections (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Stiftelsen Tornspiran
- European Commission (HORIZON2020, 634880)
- Stiftelsen Olle Engkvist Byggmästare
- Vetenskapsrådet
- Sällskapet Barnavård
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- fetal adrenal gland, androgen production, dihydrotestosterone, steroidogenesis, first trimester, CYP17A1, SF-1, GATA6, testosterone, androsterone, steroidogenic enzymes, transcription factors
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