Neural systems underlying photoperiodic time measurement: A blueprint

Summary This paper briefly reviews the formal properties of the photoperiodic time measurement apparatus of mammals and presents a hypothetical model for the operation of the neural systems responsible for reading and responding to the nocturnal pineal melatonin signal. The primary melatonin readout mechanism is held to be common to all species responsive to melatonin. It seems likely that this mechanism responds to relative changes in the duration and amplitude of the melatonin signal, rather than the absolute levels of melatonin encountered. A series of neural systems which exploit the calendar information provided by the primary readout is envisaged to vary between and within species, depending upon the neuroendocrine response under consideration. Of particular importance is a mechanism for comparing the relative duration of successive melatonin signals. These more complex elements are responsible for phenomena such as the effects of photopheriodic history and photorefractoriness. The brain may be able to encode an accumulated memory of melatonin signals and thereby define longer term intervals within the annual cycle. A series of response elements within the hypothalamus are engaged by the appropriately processed photoperiodic stimuli. For all elements of this model, their anatomical representations are poorly understood or, in certain cases, completely unknown.     

Some reflections on the phylogeny and function of the pineal

The pineal gland is a universal feature of vertebrate organization and has been implicated in the control of rhythmic adaptations to daily and seasonal cycles. This paper considers three aspects of pineal function; the generation of a rhythmical endocrine signal (the nocturnal synthesis of melatonin) and the use of the signal in the regulation of circadian and photoperiodic functions. The shape of the nocturnal signal is determined by an interaction of afferent neural control and biochemical processes intrinsic to the pinealocyte. The nature of the effect of the signal upon circadian systems is unclear, and in adult mammals may not be a specific, direct influence upon the entrainment pathways of the oscillator. In the foetus, strong evidence exists for a physiological role of the maternal melatonin signal as a true internal zeitgeber, remnants of which may persist in the adult. Photoperiodic time measurement in adult and foetal mammals is critically dependent upon the melatonin signal. Indirect evidence indicates that several neural systems may be involved in the response to melatonin and consistent with this, a variety of central melatonin binding sites have been identified in the brain and pituitary. The intra-cellular actions of melatonin and the properties of melatonin responsive neural systems have yet to be identified, but in the context of photoperiodic time measurement, it is clear that the neural responses to melatonin are not dependent upon the circadian clock. The two central effects of melatonin; photoperiodic time measurement and circadian entrainment are probably mediated through completely separate mechanisms.     

Some reflections on the phylogeny and function of the pineal

Summary The pineal gland is a universal feature of vertebrate organization and has been implicated in the control of rhythmic adaptations to daily and seasonal cycles. This paper considers three aspects of pineal function; the generation of a rhythmical endocrine signal (the nocturnal synthesis of melatonin) and the use of the signal in the regulation of circadian and photoperiodic functions. The shape of the nocturnal signal is determined by an interaction of afferent neural control and biochemical processes intrinsic to the pinealocyte. The nature of the effect of the signal upon circadian systems is unclear, and in adult mammals may not be a specific, direct influence upon the entrainment pathways of the oscillator. In the foetus, strong evidence exists for a physiological role of the maternal melatonin signal as a true internal zeitgeber, remnants of which may persist in the adult. Photoperiodic time measurement in adult and foetal mammals is critically dependent upon the melatonin signal. Indirect evidence indicates that several neural systems may be involved in the response to melatonin and consistent with this, a variety of central melatonin binding sites have been identified in the brain and pituitary. The intra-cellular actions of melatonin and the properties of melatonin responsive neural systems have yet to be identified, but in the context of photoperiodic time measurement, it is clear that the neural responses to melatonin are not dependent upon the circadian clock. The two central effects of melatonin; photoperiodic time measurement and circadian entrainment are probably mediated through completely separate mechanisms.The Editors wish to thank Dr M. Hastings for coordinating this multi-author review.     

Pineal melatonin rhythms and the timing of puberty in mammals

Summary The direction of change in daylength provides the seasonal time cue for the timing of puberty in many mammalian species. The pattern of melatonin secretion from the pineal gland transduces the environmental light-dark cycle into a signal influencing the neuroendocrine control of sexual maturation. The change in duration of nocturnal melatonin secretion is probably the key feature of the melatonin signal which conveys daylength information. This information may also be used by neuroendocrine axes controlling seasonal changes in pelage colour, growth and metabolism. The mechanism of action of melatonin on neuroendocrine pathways is unknow. Although the ability to synthesize and secrete melatonin in a pattern that reflects the duration of the night may not occur until the postnatal period, the rodent and ovine foetus has the ability to respond in utero to photoperiodic cues to which its mother is exposed in late gestation. Transplacental passage of maternal melatonin is likely to be the mechanism by which photoperiodic cues reach the foetus. Species which do not exhibit seasonal patterns of puberty, such as the human, also secrete melatonin in a pattern which reflects the environmental light-dark cycle, but they do not respond reproductively to the seasonal melatonin information.     

Pineal melatonin rhythms and the timing of puberty in mammals

The direction of change in daylength provides the seasonal time cue for the timing of puberty in many mammalian species. The pattern of melatonin secretion from the pineal gland transduces the environmental light-dark cycle into a signal influencing the neuroendocrine control of sexual maturation. The change in duration of nocturnal melatonin secretion is probably the key feature of the melatonin signal which conveys daylength information. This information may also be used by neuroendocrine axes controlling seasonal changes in pelage colour, growth and metabolism. The mechanism of action of melatonin on neuroendocrine pathways is unknown. Although the ability to synthesize and secrete melatonin in a pattern that reflects the duration of the night may not occur until the postnatal period, the rodent and ovine foetus has the ability to respond in utero to photoperiodic cues to which its mother is exposed in late gestation. Transplacental passage of maternal melatonin is likely to be the mechanism by which photoperiodic cues reach the foetus. Species which do not exhibit seasonal patterns of puberty, such as the human, also secrete melatonin in a pattern which reflects the environmental light-dark cycle, but they do not respond reproductively to the seasonal melatonin information.     

Melatonin: presence and formation in invertebrates

In vertebrates, it is now clearly demonstrated that the pineal gland is implicated in conveying photoperiodic information via the daily pattern of melatonin secretion. Invertebrates, like vertebrates, use photoperiodic changes as a temporal cue to initiate physiological processes such as reproduction or diapause. How this information is integrated in invertebrates remains an unsolved question. Our review will be an attempt to evaluate the possible role of melatonin in conveying photoperiodic information in invertebrates. It is now well demonstrated in both vertebrates and invertebrates that melatonin as well as its precursors or synthesizing enzymes are present in various organs implicated in photoreceptive processes or in circadian pacemaking. Melatonin, serotonin or N-acetyltransferase have been found in the head, the eyes, the optic lobe and the brain of various invertebrate species. In some species it has also been shown that melatonin is produced rhythmically with high concentrations reached during the dark period. Moreover, the physiological effects of melatonin on various periodic processes such as rhythmic contractions in coelenterates, fissioning of asexual planarians or reproductive events in flies have been reported in the literature. All these results support the hypothesis (refs 36, 37) that melatonin is not solely a pineal hormone but that it may be an evolutionary conservative molecule principally involved in the transduction of photoperiodic information in all living organisms.     

Mammalian pineal melatonin: a clock for all seasons

The central role of the pineal gland and its hormone melatonin (MEL) in mammalian photoperiodic responses is discussed in terms of: 1) evidence for the involvement of MEL in photoperiodism, 2) which feature of the MEL secretion profile might be most important for regulating photoperiodic responses, 3) evidence for the modulation of responses to changes in daylength based on previous photoperiod exposure (i.e., photoperiodic history) and 4) how the MEL signal might be processed at its target sites to elicit physiological responses.     

Threshold and quantitative photoperiodic responses exist in an insect

The photoperiodic response for the induction of adult diapause and that for the determination of nymphal body coloration were compared inPlautia stali Scott (Heteroptera: Pentatomidae). The former was an all-or-none response with a distinct threshold, but the latter was a graded response which varied quantitatively with the photophase duration. The photoperiodic clock in this species is discussed.     

Mammalian pineal melatonin: A clock for all seasons

Summary The central role of the pineal gland and its hormone melatonin (MEL) in mammalian photoperiodic responses is discussed in terms of: 1) evidence for the involvement of MEL in photoperiodism, 2) which feature of the MEL secretion profile might be most important for regulating photoperiodic responses, 3) evidence for the modulation of responses to changes in daylength based on previous photoperiod exposure (i.e., photoperiodic history) and 4) how the MEL signal might be processed at its target sites to elicit physiological responses.     

Photoperiodic induction of diapause in an insect is vitamin A dependent

Summary A photoperiodic response was found to be absent in larvae of the parasitoid waspApanteles glomeratus when its host (caterpillars ofPieris brassicae) was reared on a low-carotenoid artificial diet. Addition of vitamin A to the host's diet restored the response to short-day photoperiods in the wasp larvae, thus showing that vitamin A is essential for photoperiodic induction of diapause. Possibly vitamin A or a derivative of vitamin A functions as the photoreceptor pigment for the photoperiodic reaction in this species of insect.     

Melatonin biosynthesis in the thymus of humans and rats

Melatonin is an indoleamine widely distributed in the evolution that shows a great functional versatility, playing an important role as a transmitter of photoperiodic information and exhibiting antioxidant, oncostatic, anti-aging and immunomodulatory properties. In vertebrates, this molecule is produced by the pineal gland and other extrapineal sites. The present study was carried out to investigate the presence of melatonin in thymus and the possibility of an endogenous melatonin synthesis in this organ, in which T cells are matured. In this work, we demonstrate in humans and rats that thymus contains melatonin, expresses the mRNAs encoding N-acetyltransferase and hydroxyindol-O-methyltransferase, the two key enzymes of the melatonin synthesis, and has this biosynthetic machinery activated. In addition, rat thymocytes cultured for 24 h exhibited high levels of melatonin. The results presented here suggest that human and rat thymuses are able to synthesize melatonin, which could have intracrine, autocrine and paracrine functions. Received 30 September 2006; received after revision 30 December 2006; accepted 15 February 2007     

Indoleamines and the UV-light-sensitive photoperiodic responses of the melanocyte network: a biological calendar?

The pineal, serotoninergic and pigmented neurons are associated with light-dependent sleep/arousal, serving as a biological clock with a circadian rhythm. This rhythm is maintained by melatonin which serves to recognise the dark phase. The neural network that responds to seasonal variations in day/night length has not been identified. The present study demonstrates that melanocytes in human skin respond to changes in the duration of UV exposure, and can serve as a biological calendar. These responses are mediated by two indoleamines, serotonin and melatonin. Higher melatonin levels correspond to long nights and long days (short UV pulse), while high serotonin levels in the presence of melatonin reflect short nights and long days (long UV exposure). This response recapitulates the sleep/arousal patterns in animals exposed to large variations in day/night cycle that cause changes in coat colour from pure white in winter to complete repigmentation in summer.     

Structures and molecules involved in generation and regulation of biological rhythms in vertebrates and invertebrates

Melatonin from the retina and the pineal gland functions in neuroendocrine hierarchies. Photoreceptors — eyes and extraretinal — detect light. Oscillators — pineal and suprachiasmatic nuclei — act as pacemakers. Driven neuroendocrine rhythms carry temporal hormone signals throughout the body. Light controls melatonin: light sets the phase of the melatonin rhythm and determines the duration of melatonin synthesis. By these means, circadian rhythms (e.g. in locomotor activity and body temperature) and seasonal rhythms (e.g. in reproduction) are controlled.     

The melatonin rhythm: both a clock and a calendar

The paper briefly reviews the data which shows that the circadian production and secretion of melatonin by the pineal gland can impart both daily, i.e., clock, and seasonal, i.e., calendar, information to the organism. The paper summarizes the 3 patterns of nocturnal melatonin production that have been described. Clearly, regardless of the pattern of nocturnal melatonin production a particular species normally displays, the duration of nightime elevated melatonin is proportional to the duration of the night length. Since daylength under natural conditions changes daily the melatonin rhythm, which adjusts to the photoperiod sends time of year information to the organism. The melatonin receptors which subserve the clock message sent by the pineal gland in the form of a melatonin cycle may reside in the biological clock itself, namely, the suprachiasmatic nuclei (SCN). The melatonin receptors that mediate seasonal changes in reproductive physiology are presumably those that are located on the pars tuberalis cells of the anterior pituitary gland. Besides these receptors which likely mediate clock and calendar information, melatonin receptors have been described in other organs. Interestingly, the distribution of melatonin receptors is highly species-specific. Whereas the clock and calendar information that the melatonin cycle imparts to the organism relies on cell membrane receptors, a fact that is of some interest considering the high lipophilicity of melatonin, recent studies indicate that other functions of melatonin may require no receptor whatsoever.     

Photoperiodic effects in the Djungarian hamster: one minute of light during darktime mimics influence of long photoperiods on testicular recrudescence, body weight and pelage colour

In male Djungarian hamsters (Phodopus sungorus) short photoperiods (L/D 8/16) with additional 1- or 5-min light-pulses 8 h after light-off were as effective as long photoperiods (L/D 16/8) in stimulating testicular recrudescence, increase in body weight and moult into summer pelage. The results are discussed with regard to the hypothesis that the pattern of melatonin release from the pineal gland is important in mediating photoperiodic effects in mammals.     

Daily melatonin injections inhibit short-day-induced testicular regression in hamsters

Summary Daily injections of melatonin were found to retard testicular regression in hamsters exposed to LD 10:14, if the injections occurred in the morning (i.e., 0.5 h after lights on), but not if they occurred in the afternoon (i.e., 6 h after lights on). These results indicate that appropriately timed injections of melatonin can at least partially block the inhibitory effects of short days on gonadal activity in the photoperiodic hamster.We wish to thank Susan Losee and Susan Stice for excellent technical assistance and Gary Ellis for his comments. This investigation was supported by NIH grants HD-09885, HD 12622 and Research Career Development Award HD-00249 (F. W. T.) from the National Institute of Child Health and Human Development.     

Occurrence of retinal and 3-hydroxyretinal in a possible photoreceptor of the silkworm brain involved in photoperiodism

Summary Deficiency of dietary carotenoid and vitamin A caused an absence of photoperiodic response of diapause induction in the silkworm,Bombyx mori, and an addition of vitamin A to the diet restored the response. By high pressure liquid chromatography (HPLC) a possible photoperiodic receptor of the silkworm brain was found to contain both retinal and 3-hydroxyretinal which are chromophores of insect visual pigments. These pieces of evidence suggest that a retinoid protein might function in the photoperiodic response of the silkworm.