Daily Changes in GT1–7 Cell Sensitivity to GnRH Secretagogues That Trigger Ovulation

Circadian rhythms in behavior and physiology are orchestrated by a master biological clock located in the suprachiasmatic nucleus (SCN). Circadian oscillations are a cellular property, with 'clock' genes and their protein products forming transcription-translation feedback loops that maintain 24-hour rhythmicity. Although the expression of clock genes is thought to be ubiquitous, the function of local, extra-SCN timing mechanisms remains elusive. We hypothesized that extra-SCN clock genes control local temporal sensitivity to upstream modulatory signals, allowing system-specific processes to be carried out during individual, optimal times of day. To test this possibility, we examined changes in the sensitivity of immortalized GnRH neurons, GT1-7 cells, to timed stimulation by two key neuropeptides thought to trigger ovulation on the afternoon of proestrus, kisspeptin and vasoactive intestinal polypeptide (VIP). We noted a prominent daily rhythm of clock gene expression in this cell line. GT1-7 cells also exhibited daily changes in cellular peptide expression and GnRH secretion in response to kisspeptin and VIP stimulation. These responses occurred without changes in GnRH transcription. These findings are consistent with the notion that GnRH cells are capable of intrinsic circadian cycles that may be fundamental for coordinating daily changes in sensitivity to signals impacting the reproductive axis.