Molecular Characterization of the Long-Day Response in the Soay Sheep, a Seasonal Mammal

In mammals, seasonal timekeeping depends on the generation of a nocturnal melatonin signal that reflects nightlength/daylength. To understand the mechanisms by which the melatonin signal is decoded, we studied the photoperiodic control of prolactin secretion in Soay sheep, which is mediated via melatonin responsive cells in the pars tuberalis of the pituitary. We demonstrate that the phases of peak expression of the clock genes Cryptochrome1 (Cry1), Period1 (Per1), and RevErbalpha respond acutely to altered melatonin secretion after a switch from short to long days. Cry1 is activated by melatonin onset, forming the dusk component of the molecular decoder, while Per1 expression at dawn reflects the offset of melatonin secretion. The Cry1-Per1 interval immediately adjusts to the melatonin signal on the first long day, and this is followed within 24 hr by an increase in prolactin secretion. The timing of peak RevErbalpha expression also responds to a switch to long days due to altered melatonin secretion but does not immediately reset to an entrained long-day state. These data suggest that effects of melatonin on clock gene expression are pivotal events in the neuroendocrine response and that pars tuberalis cells can act as molecular calendars, carrying a form of "photoperiodic memory."