Fos-related antigen 2 (Fra-2) memorizes photoperiod in the rat pineal gland

As the physiological role of fos-related antigen-2 (Fra-2) is largely unknown and since the pineal plays an important role in the photoperiodic control of the body, we have tested the hypothesis that Fra-2 expression is photoperiod-dependent and may be involved in imprinting photoperiod on the pineal gland and the body as a whole. To this end, we have investigated Fra-2 mRNA expression and Fra-2 protein expression under various light/dark (LD) cycles. A clear nocturnal increase occurs for both monitored parameters under all photoperiodic conditions studied. The level of Fra-2 protein expression clearly depends on photoperiod, because the amount of protein at dark onset and during the night negatively correlates with the length of the photoperiod. Further, high-phosphorylated Fra-2 isoforms are abundant under all photoperiods tested, with the exception of LD 20:4. Because Fra-2 phosphorylation depends on cGMP, a depressed cGMP response to adrenergic stimulation under LD 20:4 appears to explain this finding. We conclude that photoperiod is imprinted on Fra-2 in terms of both protein amount and protein phosphorylation in the rat pineal gland. This imprinting becomes fully manifest after about 7 days only, suggesting that a number of altered photoperiodic cycles are required for pineal Fra-2 to "learn" that the photoperiod has changed. Reportedly, Fra-2 limits expression of the enzyme iodothyronine deiodinase type II, which catalyzes the intracellular deiodination of thyroxine prohormone to the active 3,3',5-triiodothyronine. We have found that the extent of Fra-2 expression inversely correlates with the dII gene response to cAMP; hence the photoperiodic regulation of Fra-2 may affect the body by changing pineal thyroid hormone metabolism.