Androgenic potential of human fetal adrenals at the end of the first trimester
| Autor: | Olle Söder, Marie-Line Morvan, B. Le Bizec, Iuliia Savchuk, Kristina Gemzell-Danielsson, J. P. Antignac, Konstantin Svechnikov |
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| Přispěvatelé: | Svechnikov, K., University Hospital, Karolinska Institutet [Stockholm], Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), LUNAM Université [Nantes Angers Le Mans], Department of Obstetrics and Gynecology, Helsinki University Central Hospital, European Union's Horizon research and innovation programme [634880], Swedish Research Council, Children's Cancer Fund, Frimurare Barnhuset Foundation, Kronprinsessan Lovisas Foundation, Sallskapet Barnavard, Stiftelsen Sigurd och Elsa Goljes Minne, Stiftelsen Olle Engkvist Byggmastare, Stiftelsen Gunvor och Josef Aners, Stiftelsen Jane och Dan Olssons, Stiftelsen Tornspiran |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty genetic structures human fetal adrenals steroidogenic enzyme expression androgens steroid profiles medicine.drug_class Endocrinology Diabetes and Metabolism [SDV]Life Sciences [q-bio] 030209 endocrinology & metabolism lcsh:Diseases of the endocrine glands. Clinical endocrinology behavioral disciplines and activities 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Androstanedione Internal medicine mental disorders Internal Medicine Medicine Transcription factor Testosterone Androsterone lcsh:RC648-665 business.industry Research Androgen Blot 030104 developmental biology chemistry CYP17A1 Immunohistochemistry business |
| Zdroj: | Endocrine Connections 6 (6), 348-359. (2017) Endocrine Connections Endocrine Connections, BioScientifica Ltd., 2017, 6 (6), pp.348-359. ⟨10.1530/EC-17-0085⟩ Endocrine Connections, Vol 6, Iss 6, Pp 348-359 (2017) |
| ISSN: | 2049-3614 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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