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.
Engel
L
L
Department of Anatomy, Johannes Gutenberg University, Saarstrasse 19-21, D-55099 Mainz, Germany.
Gupta
B B P
BB
Lorenzkowski
V
V
Heinrich
B
B
Schwerdtle
I
I
Gerhold
S
S
Holthues
H
H
Vollrath
L
L
Spessert
R
R
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000222:Adaptation, Physiological; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D051921:Fos-Related Antigen-2; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006360:Heat-Shock Proteins / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D017440:Photoperiod; D010870:Pineal Gland / Q000378:metabolism* / Q000528:radiation effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004268:DNA-Binding Proteins; D051921:Fos-Related Antigen-2; C497874:Fosl2 protein, rat; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D014157:Transcription Factors; C063820:SNP nonapeptide; D010656:Phenylephrine; D000242:Cyclic AMP; D000123:Acetyltransferases; D006152:Cyclic GMP; D007545:Isoproterenol