Maestro: A Possible Conductor of the Ovulatory Symphony

Abstract

Maestro (MRO) is a transcription factor that has a role in regulating gene expression. The MRO expression pattern was examined in a unique set of human granulosa cells (GCs) and follicles collected across the ovulatory period of a natural menstrual cycle. MRO mRNA was elevated (70-fold) in women during the early ovulatory phase (12h to ≤18h post hCG administration; LH analog) and remained elevated (35-fold) in the late ovulatory phase (>18h to ≤ 34h) when compared to the preovulatory state (before the LH surge). Immunohistochemistry of whole follicles from women demonstrated positive MRO signal in GCs during the early and late ovulatory phases. Employing a cultured human granulosa luteal cell (hGLCs) model, we further examined MRO regulation in human granulosa cells from IVF patients. Treating hGLCs in vitro with hCG elevated MRO expression by 22-fold at 6h, 48-fold at 12h, and then expression slightly decreased to 13-fold at 24h. Similarly, the strongest MRO protein expression was detected at 12h. Next, LH/hCG signaling pathways regulating MRO expression were investigated using inhibitors specific to each signaling pathway. Our data revealed that hCG regulated MRO expression through LH-dependent classical signaling pathways such as PKA, PKC, and PI3K, with MAPK partially regulating its expression. Moreover, the EGF and progesterone pathways, important in the periovulatory period, were found to be involved in MRO regulation. These data, taken together, demonstrate that MRO is poised to play a role in the coordination of periovulatory events through the EGF and progesterone signaling pathways.