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.

中文翻译：

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ACTH 和催乳素协同并选择性地调节人胎儿肾上腺器官培养物中 CYP17 的表达和肾上腺雄激素的产生。

目的 ACTH 对人类胎儿肾上腺 (HFA) 生长和功能的重要作用早已被认识到。此外，许多研究表明垂体激素催乳素（PRL）在 HFA 的调节中发挥作用，但这种激素对类固醇生成和基因表达的影响仍不清楚。我们的目的是研究 ACTH 和 PRL 对 HFA 类固醇生成能力的影响。设计体外/离体实验研究。方法我们使用悬滴体外器官培养系统。妊娠早期 HFA 样品在基础条件下培养 14 天，或用 ACTH、PRL 或两者的组合处理（根据实验重复 3 至 11 次）。通过液相色谱/串联质谱法或免疫测定法测量类固醇，通过RT-qPCR测量基因表达，并通过免疫印迹测量蛋白质表达。结果 ACTH 单独使用以及与 PRL 一起使用时均显着增加皮质酮、皮质醇和可的松的产生。PRL 刺激本身没有效果。ACTH + PRL 联合刺激可协同选择性地增加 HFA 中肾上腺雄激素（DHEAS 和 Δ4-雄烯二酮）的产生和 CYP17A1 表达，而每种单一激素治疗对这些类固醇没有显着影响。结论 这些结果对于我们理解妊娠早期在生理和病理条件下调节 HFA 中肾上腺类固醇生成的激素线索具有重要意义，并需要进一步研究来表征 ACTH 和 PRL 信号融合以调节 CYP17A1 表达的分子机制。