YPEL4 modulates HAC15 adrenal cell proliferation and is associated with tumor diameter

• YPEL4 stimulated cell proliferation in HAC15.
• The increase of aldosterone production paralleled the increase in cell proliferation.
• YPEL4 had no effects on the expression of steroidogenic enzymes.
• APA had higher YPEL4 levels compared to non-functional adenomas.
• The tumor diameter associated with YPEL4 levels in APA samples.

Yippee-like (YPEL) proteins are thought to be related to cell proliferation because of their structure and location in the cell. The aim of this study was to clarify the effects of YPEL4 on aldosterone production and cell proliferation in the human adrenocortical cell line (HAC15) and aldosterone producing adenoma (APA). Basal aldosterone levels in HAC15 cells over-expressing YPEL4 was higher than those of control HAC15 cells. The positive effects of YPEL4 on cell proliferation were detected by XTT assay and crystal violet staining. YPEL4 levels in 39 human APA were 2.4-fold higher compared to those in 12 non-functional adrenocortical adenomas, and there was a positive relationship between YPEL4 levels and APA diameter (r = 0.316, P < 0.05). In summary, we have demonstrated that YPEL4 stimulates human adrenal cortical cell proliferation, increasing aldosterone production as a consequence. These results in human adrenocortical cells are consistent with the clinical observations with APA in humans.