Adrenocortical tumors (ACTs) frequently cause steroid excess and present cell-cycle dysregulation. cAMP/PKA signaling is involved in steroid synthesis and play a role in cell-cycle regulation. We investigated, by cell synchronization in the different phases of the cell-cycle, the control of steroidogenesis and the contribution of PKA in adrenocortical cells (H295R and culture of primary pigmented nodular adrenocortical disease cells). Cells showed increased steroidogenesis and a maximal PKA activity at G2 phase, and a reduction at G1 phase. PRKACA overexpression, or cAMP stimulation, enhanced PKA activity and induced steroidogenesis in all synchronized groups but is not sufficient to drive cell-cycle progression. PRKAR1A inactivation enhanced PKA activity and induced STAR gene expression, only in cells in G1, and triggered cell-cycle progression in all groups. These findings provide evidence for a tight association between steroidogenesis and cell-cycle in ACTs. Moreover, PRKAR1A is essential for mediating the function of PKA activity on both steroidogenesis and cell-cycle progression in adrenocortical cells.

中文翻译：

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肾上腺皮质肿瘤细胞中类固醇生成，细胞周期和PKA之间的联系。

肾上腺皮质肿瘤（ACTs）经常导致类固醇过多并出现细胞周期失调。cAMP / PKA信号传导参与类固醇合成，并在细胞周期调控中发挥作用。我们通过在细胞周期的不同阶段进行细胞同步研究了类固醇生成的控制和肾上腺皮质细胞（H295R和原发性色素性结节性肾上腺皮质疾病细胞的培养）中PKA的贡献。细胞在G2期显示出更高的类固醇生成和最大的PKA活性，而在G1期则降低。PRKACA过表达或cAMP刺激，在所有同步组中均增强了PKA活性并诱导了类固醇生成，但不足以驱动细胞周期进程。PRKAR1A失活仅在G1细胞中增强PKA活性并诱导STAR基因表达，并触发所有组的细胞周期进程。这些发现为ACTs中类固醇生成与细胞周期之间的紧密联系提供了证据。此外，PRKAR1A对于介导肾上腺皮质细胞中类固醇生成和细胞周期进程中PKA活性的功能至关重要。