Mediates GnRH Secretion via System in GT1-7 Cells.

STUDY OBJECTIVE

The well-known tumor suppressor transcriptional factor has been proposed to be one of the central hubs of a functionally related and hierarchically arranged gene network coordinating pubertal timing. Our previous studies revealed that is involved in the metabolic control of puberty. The current study aimed to investigate the underlying signaling pathway, through which mediated the metabolic control of puberty.

DESIGN SETTING PARTICIPANTS INTERVENTIONS AND MAIN OUTCOME MEASURES

We engineered the expression of and/or in GT1-7 cells to investigate the interaction between and system, and their impact on GnRH secretion.

RESULTS

Overexpression of stimulated, while inhibition of by pifithrin-α significantly suppressed the GnRH secretion and expression levels in response to kisspeptin stimulation in GT1-7 cells. Furthermore, overexpressed suppressed and expression levels and increased expression levels in GT1-7 cell lines. On the other hand, inhibition of by pifithrin-α upregulated and c-Myc levels and downregulated expression levels. Moreover, overexpression counteracted the effect of overexpression in and co-overexpression cells, whose GnRH secretion and GPR54 expression levels were not different from controls. Meanwhile, suppression counteracted the effect of pifithrin-α, and the GnRH secretion and expression levels are not different from controls in and co-suppression cells.

CONCLUSION

These data suggest that is a central mediator of GnRH secretion in hypothalamus, and this effect is at least partly through the pathway.