The Pineal Gland: Photoreception and Coupling of Behavioral, Metabolic, and Cardiovascular Circadian Outputs

Abstract

Although removal of the pineal gland has been shown to have very little effect on the mammalian circadian system in constant darkness (DD), several recent reports have suggested that the mammalian pineal gland may be more important for circadian organization in nocturnal rodents than was previously believed. Removal of the pineal gland (PINX) facilitates the disruptive effects of constant bright light on wheel-running rhythmicity. This suggests at least two possibilities for the role of the pineal gland in the mammalian circadian system. First, pinealectomized rats may perceive ambient light intensity to be brighter than do sham-operated (SHAM) rats. Second, the pineal gland, probably via its secretion of melatonin, may also be involved in coupling components of the circadian system. Coupling, as we see it, may occur at several levels of organization: (1) between retinohypothalamic afferents and suprachiasmatic nuclei (SCN) oscillatory neurons, (2) among multiple SCN oscillators, (3) between the SCN and their multiple outputs, and/or (4) among the multiple circadian outputs themselves. In this study we show that PINX rats free-run with a longer period in four different light intensities than do SHAM rats. Moreover, the rate of increase of tau is greater among PINX rats than among SHAM rats. This supports the first hypothesis. We also show that in PINX rats the circadian rhythms of wheel running, general activity, body temperature, and heart rate are all more disrupted in constant bright light than are those of SHAM rats, and each rhythmic output is disrupted in parallel. This supports the second hypothesis. Melatonin is probably not involved in coupling presynaptic elements of SCN afferents in the retinohypothalamic tract to pacemaking cells within the SCN, since enucleation has no effect on SCN 2-[125I]iodomelatonin (IMEL) binding. Together the data do not discount either of the two hypotheses but do restrict the possible levels at which the pineal gland is involved in coupling. These data also further support a growing body of literature indicating that the pineal gland and its hormone melatonin play a role in mammalian circadian organization.

Protective effect of maternal prenatal melatonin administration on rat pups born to mothers submitted to constant light during gestation

“…These effects of LL on the maternal SCN were prevented by maternal melatonin administration during the last period of gestation. Our results are consistent with previous studies (6,7,11,12,30), confirm the importance of the melatonin signal and provide evidence of the protective effects of the hormone on maternal programming during gestation.…”

7α-Hydroxypregnenolone Mediates Melatonin Action Underlying Diurnal Locomotor Rhythms

“…We hypothesized that melatonin may regulate 7␣-hydroxypregnenolone synthesis, thus influencing locomotor activity. We based our hypothesis on evidence that melatonin is involved in the regulation of locomotor activity in birds (Binkley et al, 1971;John et al, 1978;Cassone and Menaker, 1984;Chabot and Menaker, 1992;Hau and Gwinner, 1994;Warren and Cassone, 1995;Murakami et al, 2001) and on our observations of parallel changes in locomotor activity and 7␣-hydroxypregnenolone synthesis. Our hypothesis was confirmed by a combination of experiments involving melatonin manipulation in male quail.…”

“…In contrast, females showed constantly lower levels of 7␣-hydroxypregnenolone synthesis and locomotor activity. Finally, we investigated the mechanism that regulates diurnal changes in 7␣-hydroxypregnenolone synthesis in males based on evidence that melatonin controls diurnal changes in locomotor activity in birds (Binkley et al, 1971;John et al, 1978;Cassone and Menaker, 1984;Chabot and Menaker, 1992;Hau and Gwinner, 1994;Warren and Cassone, 1995). Here, we show that melatonin regulates synthesis of 7␣-hydroxypregnenolone, a key factor for induction of locomotor activity, thus inducing diurnal locomotor rhythms in male birds.…”

“…The endogenous diurnal rhythm of melatonin is known to control the diurnal locomotor rhythm in vertebrates, including birds (Binkley et al, 1971;John et al, 1978;Cassone and Menaker, 1984;Chabot and Menaker, 1992;Hau and Gwinner, 1994;Warren and Cassone, 1995). However, molecular mechanisms for this neurohormonal regulation of behavior are poorly understood.…”

Biosynthesis and Biological Actions of Pineal Neurosteroids in Domestic Birds

“…It is known that in birds and other vertebrates, the locomotor activity undergoes a circadian change [68] controlled by the diurnal rhythm of melatonin secretion [69,70,71,72,73,74]. The discovery of the role of 7α-hydroxypregnenolone in mediating the action of melatonin on diurnal locomotor rhythmicity is an important step in understanding the molecular mechanism underlying melatonin regulation of the behavior [66].…”