Melatonin synthesis and clock gene regulation in the pineal organ of teleost fish compared to mammals: Similarities and differences.

The pineal organ of all vertebrates synthesizes and secretes melatonin in a rhythmic manner due to the circadian rhythm in the activity of arylalkylamine N-acetyltransferase (AANAT) - the rate-limiting enzyme in melatonin synthesis pathway. Nighttime increase in AANAT activity and melatonin synthesis depends on increased expression of aanat gene (a clock-controlled gene) and/or post-translation modification of AANAT protein. In mammalian and avian species, only one aanat gene is expressed. However, three aanat genes (aanat1a, aanat1b, and aanat2) are reported in fish species. While aanat1a and aanat1b genes are expressed in the fish retina, the nervous system and other peripheral tissues, aanat2 gene is expressed exclusively in the fish pineal organ. Clock genes form molecular components of the clockwork, which regulates clock-controlled genes like aanat gene. All core clock genes (i.e., clock, bmal1, per1, per2, per3, cry1 and cry2) and aanat2 gene (a clock-controlled gene) are expressed in the pineal organ of several fish species. There is a large body of information on regulation of clock genes, aanat gene and melatonin synthesis in the mammalian pineal gland. However, the information available on clock genes, aanat genes and melatonin synthesis in photoreceptive pineal organ of teleosts is fragmentary and not well documented. Therefore, we have reviewed published information on rhythmic expression of clock genes, aanat genes as well as synthesis of melatonin, and their regulation by photoperiod and temperature in teleostean pineal organ as compared to mammalian pineal gland. A critical analysis of the literature suggests that in contrast to the mammalian pineal gland, the pineal organ of teleosts (except salmonids) possesses a well developed indigenous clock composed of clock genes for regulation of rhythmic expression of aanat2 gene and melatonin synthesis. Further, the fish pineal organ also possesses essential molecular components for responding to light and temperature directly. The fish pineal organ seems to act as a potential master biological clock in most of the teleosts.