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ACTH and prolactin synergistically and selectively regulate CYP17 expression and adrenal androgen production in human foetal adrenal organ cultures.
Schneider, Grégoire; Ruggiero, Carmen; Renault, Lucie; Doghman-Bouguerra, Mabrouka; Durand, Nelly; Hingrai, Guillaume; Dijoud, Frédérique; Plotton, Ingrid; Lalli, Enzo.
Afiliação
  • Schneider G; Department of Pediatric Surgery, University Hospital of Lyon, 69002 Lyon, France.
  • Ruggiero C; Claude Bernard Lyon 1 University, 69100 Villeurbanne, France.
  • Renault L; Institut de Pharmacologie Moléculaire et Cellulaire CNRS UMR 7275, 06560 Valbonne, France.
  • Doghman-Bouguerra M; Université Côte d'Azur, 06560 Valbonne, France.
  • Durand N; Claude Bernard Lyon 1 University, 69100 Villeurbanne, France.
  • Hingrai G; Reproductive Medicine and Biology, University Hospital of Lyon, 69002 Lyon, France.
  • Dijoud F; Institut de Pharmacologie Moléculaire et Cellulaire CNRS UMR 7275, 06560 Valbonne, France.
  • Plotton I; Université Côte d'Azur, 06560 Valbonne, France.
  • Lalli E; Institut de Pharmacologie Moléculaire et Cellulaire CNRS UMR 7275, 06560 Valbonne, France.
Eur J Endocrinol ; 189(3): 327-335, 2023 Sep 01.
Article em En | MEDLINE | ID: mdl-37638769
OBJECTIVE: The essential role of ACTH on the growth and function of the human foetal adrenal (HFA) has long been recognized. In addition, many studies have suggested a role of the pituitary hormone prolactin (PRL) in the regulation of the HFA, but the effects of this hormone on steroidogenesis and gene expression are still unknown. Our objective was to investigate the effect of ACTH and PRL on the steroidogenic capacities of the HFA. DESIGN: In vitro/ex vivo experimental study. METHODS: We used a hanging drop in vitro organ culture system. First trimester HFA samples were cultured for 14 days in basal conditions or treated with ACTH, PRL, or a combination of the 2 (3 to 11 replicates depending on the experiment). Steroids were measured by liquid chromatography/tandem mass spectrometry or immunoassay, gene expression by RT-qPCR, and protein expression by immunoblot. RESULTS: ACTH significantly increased corticosterone, cortisol, and cortisone production, both by itself and when used together with PRL. PRL stimulation by itself had no effect. Combined stimulation with ACTH + PRL synergistically and selectively increased adrenal androgen (DHEAS and Δ4-androstenedione) production and CYP17A1 expression in the HFA, while treatment with each single hormone had no significant effect on those steroids. CONCLUSIONS: These results have important implications for our understanding of the hormonal cues regulating adrenal steroidogenesis in the HFA during the first trimester in physiological and pathological conditions and warrant further studies to characterize the molecular mechanisms of converging ACTH and PRL signalling to regulate CYP17A1 expression.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Prolactina / Androgênios Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Prolactina / Androgênios Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article