Regulation of Neuroendocrine and Ovulatory Function: It's All in the Timing

The temporal coordination of myriad physiological processes is necessary for the maintenance of homeostasis and optimal health. On a daily schedule, the management of this intricate ‘balancing act’ is orchestrated by the hypothalamic suprachiasmatic nucleus (SCN), the main circadian pacemaker in mammals. Because hormones are capable of communicating temporal information to widespread targets in the brain and body via the circulatory system, it is important to gain an understanding of the genetic, cellular, and neural mechanisms regulating endocrine timing. Traditionally, endocrinologists have focused on the role of negative feedback mechanisms and neuroendocrine pulse generators as the primary mechanisms for temporal organization of hormone secretion. Endogenous timing systems are, however, increasingly implicated in maintaining the temporal order of hormone production and release. In some instances, neurosecretion is controlled by direct synaptic connections from the mammalian circadian pacemaker located in the SCN. We have probed this mechanism by specifying the neural projections from the SCN to components of the reproductive axis that control the timing of hormonal events necessary for ovulation. In other systems, we found that neuroendocrine cells express ‘clock’ genes that regulate circadian function at the cellular level; in this way they exert direct transcriptional control over neuroendocrine releasing factors and adjust their timing accordingly. These two mechanisms likely act in concert to coordinate the precise timing of endocrine events and, ultimately, timing throughout the body. These relatively unexplored regulatory interactions represent opportunities for investigations of endogenous timing machinery responsible for promoting optimal physiological functioning.