Circadian regulation of pineal gland rhythmicity

Abstract

The pineal gland is a neuroendocrine organ of the brain. Its main task is to synthesize and secrete melatonin, a nocturnal hormone with diverse physiological functions. This review will focus on the central and pineal mechanisms in generation of mammalian pineal rhythmicity including melatonin production. In particular, this review covers the following topics: (1) local control of serotonin and melatonin rhythms; (2) neurotransmitters involved in central control of melatonin; (3) plasticity of the neural circuit controlling melatonin production; (4) role of clock genes in melatonin formation; (5) phase control of pineal rhythmicity; (6) impact of light at night on pineal rhythms; and (7) physiological function of the pineal rhythmicity.

Figure 1. Pineal gland rhythms

Dietary tryptophan is sequentially converted to 5-hydroxytryptophan (5-HTP, light blue), 5-hydroxytryptamine (5-HT, pink), N-acetylserotonin (NAS, dark blue), and melatonin (yellow). Dark shaded areas represent dark period. Pineal rhythms over 3 consecutive days in one rat were monitored by pineal microdialysis.

Figure 2. Time lag between serotonin and melatonin secretion in rodents

Serotonin release precedes melatonin release by about 1 hr in rat and 4 hrs in hamsters. In rats, the time lag is constant, regardless the strain and individual differences in timing of melatonin release.

Figure 3. The neuronal circuit that controls pineal rhythmicity

SCG: superior cervical ganglion; IML: intermediolateral nucleus of the spinal cord; PVN: paraventricular nucleus of the hypothalamus; SCN: suprachiasmatic nucleus.

Figure 4. Inter-individual and inter-strain variation of the timing of melatonin secretion in rats

Melatonin secretion, monitored from outbred Sprague Dawley (SD; n=6) and Wistar rats (n=8) and inbred PVG (n=4) and Lewis (LEW; n=4) rats, is normalized to the nocturnal peak values.