The effect of heat on rat pineal hydroxyindole-O-methyl transferase activity

Summary Exposure of adult male rats to continuously elevated temperature of 32–34°C caused a significant decrease of HIOMT activity involved in the specific metabolic process of production of melatonin, considered an active pineal hormone. The effect was already evident after 24 h exposure and increased further during the next 48 h. The results obtained substantiate previous data that the pineal gland may be involved in the system regulating adaptation to extreme temperature changes.Acknowledgment. The authors are indebted to MissUte Schmidt for her excellent technical assistance.     

The pineal and melatonin: regulators of circadian function in lower vertebrates

The pineal has been identified as a major circadian pacemaker within the circadian system of a number of lower vertebrates although other pacemaking sites have been implicated as well. The rhythmic synthesis and secretion of the pineal hormone, melatonin, is suggested as the mechanism by which the pineal controls circadian oscillators located elsewhere. Both light and temperature cycles can entrain the pineal melatonin rhythm. The pineal, therefore, acts as a photo and thermoendocrine transducer which functions to synchronize internal cycle with cycles in the environment. A model is presented which portrays the pineal as a major component of a 'multioscillator' circadian system and which suggests how these multiple circadian clocks are coupled to each other and to cycles of light and temperature in the external world.     

Development of rhythmic melatonin synthesis in cultured pineal glands and pineal cells isolated from chick embryo

The chick pineal gland exhibits circadian rhythms in melatonin synthesis under in vivo and in vitro conditions. A daily rhythm of melatonin production was first detectable in pineal glands isolated from chick embryos at embryonic day 16 and incubated under a LD cycle. All pineal glands isolated from 17-day-old and older embryos were rhythmic while no gland isolated at embryonic day 14 and 15 exhibited a daily rhythm in melatonin synthesis. Melatonin production in static cultures of embryonic pineal cells was rhythmic over 48 h if the cells were kept under a LD cycle. When embryonic pineal cells were incubated in constant darkness the rhythm in melatonin production was damped within 48 h. These results suggest that chick pineal cells from embryonic day 16 onwards are photosensitive but that the endogenous component of the melatonin rhythm is not completely developed at that age. A soluble analogue of cAMP stimulated and norepinephrine inhibited melatonin synthesis in cultured embryonic pineal cells. These findings indicate that the stimulatory and inhibitory pathways controlling melatonin synthesis in the mature pineal gland are effective in pineal cells isolated from chick embryos at least 2 days before hatching.     

Estimation of the methylating capacity of the pineal gland. With special reference to indole metabolism

In order to obtain more information on the methylating capacity of the pineal gland, a method determining the formation of different 5-methoxyindoles in the pineal gland was developed. The method depends on measuring the incorporation of labelled methyl groups into the various hydroxyindoles present in the pineal gland, after incorporation of pineal tissue with labelled S-adenosyl methionine. Hydroxyindoles were not added to the incubation medium. After incubation thin-layer chromatography was performed with pineal tissue together with the incubation medium; the spots were scraped and counted.     

The pineal and melatonin: Regulators of circadian function in lower vertebrates

Summary The pineal has been identified as a major circadian pacemaker within the circadian system of a number of lower vertebrates although other pacemaking sites have been implicated as well. The rhythmic synthesis and secretion of the pineal hormone, melatonin, is suggested as the mechanism by which the pineal controls circadian oscillators located elsewhere. Both light and temperature cycles can entrain the pineal melatonin rhythm. The pineal, therefore, acts as a photo and thermoendocrine transducer which functions to synchronize internal cycle with cycles in the environment. A model is presented which portrays the pineal as a major component of a multioscillator circadian system and which suggests how these multiple circadian clocks are coupled to each other and to cycles of light and temperature in the external world.     

The pineal and melatonin: Regulators of circadian function in lower vertebrates

Summary The pineal has been identified as a major circadian pacemaker within the circadian system of a number of lower vertebrates although other pacemaking sites have been implicated as well. The rhythmic synthesis and secretion of the pineal hormone, melatonin, is suggested as the mechanism by which the pineal controls circadian oscillators located elsewhere. Both light and temperature cycles can entrain the pineal melatonin rhythm. The pineal, therefore, acts as a photo and thermoendocrine transducer which functions to synchronize internal cycle with cycles in the environment. A model is presented which portrays the pineal as a major component of a multioscillator circadian system and which suggests how these multiple circadian clocks are coupled to each other and to cycles of light and temperature in the external world.     

Pineal N-acetyltransferase depression in rats exposed to heat

Summary Exposure of adult male rats to increased temperature of 33±1°C for 3 and 10 days brought about decreases in pineal N-acetyltransferase activity. These and previous findings of pineal HIOMT inhibition under similar conditions support the postulation of a possible thermoregulatory role for the pineal gland.     

Central neural control of pineal melatonin synthesis in the rat

To investigate a possible central neural influence on nocturnal pineal metabolic activity in rats, frontal transsections of the stria medullaris thalami were conducted. Enzymes involved in melatonin synthesis, i.e. N-acetyltransferase and hydroxyindole-O-methyl-transferase, exhibited reduced activities in operated animals when compared to controls. These results indicate a modulatory role of central structures on nocturnal pineal indole metabolism.     

Development of post-hatching melatonin rhythm in zebra finches (Poephila guttata)

We examined levels of melatonin in the pineal, eyes and plasma over a 24 h period during development in the altricial zebra finch. Beginning as early as 2 days after hatching there was a distinct 24 h rhythm in melatonin in the pineal and plasma. Beginning at day seven after hatching there was also a 24 h rhythm present in the eyes. In the pineal and eyes the amplitude of the 24 h rhythm increased with age. In contrast, the amplitude of the plasma melatonin rhythm at 2 days was already within the range of adults and did not increase with age. These results confirm and expand earlier findings in the European starling and parallel those from precocial birds indicating that the circadian system is already competent at or shortly after hatching even in atricial birds.     

Photoreceptors in the pineal of lower vertebrates: Functional aspects

Summary The pineal of lower vertebrates characteristically contains true and modified photoreceptors with functional und structural homologies to retinal photoreceptors. Afferent nerves convey photic information from the pineal to sensory areas of the brain stem. Light also influences synthetic activity within the organ, controlling the rhythm in melatonin production which is generated endogenously. The molecular mechanisms underlying this rhythmic event are described and the hypothesis advanced that the pineal transduces several forms of environmental stimulus involved in the regulation of rhythmic function.     

Ethanol ingestive behavior as a function of central neurotransmission

Uncontrollable alcohol ingestive behavior has been linked to deficits of central neurotransmission. The pineal gland plays an important role in modulating ethanol intake in numerous animal species. The opioidergic (i.e. beta-endorphin, enkephalin, and dynorphin) system is involved in both the actions of alcohol and opiates, as well as craving and/or genetic predisposition towards abuse of these two agents. Furthermore, there is significant evidence to link ingestive behaviors with the ventral tegmental accumbens-hypothalamic axis, whereby the biogenic amines dopamine and serotonin are reciprocally involved. Evidence is presented which implicates the striatum and the hypothalamus as possible specific loci for regional differences between alcohol-preferring and alcohol-nonpreferring mice. We believe that photoperiod-induced alcohol ingestive behavior may involve alterations in both pineal and hypothalamic opioid peptides.     

Central neural control of pineal melatonin synthesis in rat

Summary To investigate a possible central neural influence on nocturnal pineal metabolic activity, frontal transsections of the stria medullaris thalami were conducted. Enzymes involved in melatonin synthesis, i.e. N-acetyltransferase and hydroxyindole-O-methyl-transferase, exhibited reduced activities in operated animals when compared to controls. These results indicate a modulatory role of central structures on noctural pineal indole metabolism.This study was supported by the Deutsche Forschungsgemeischaft and the Stifung Volkswagenwerk. The technical assistance provided by M. Henschel, I. v. Graevenitz and G. Schlich is gratefuly acknowledged.     

Development of melatonin rhythm in the pineal gland and eyes of chick embryo.

A melatonin rhythm was observed in the pineals of 18-day-old chick embryos incubated under a light-dark regime of 18: 6 h. A low pineal melatonin content was found during the light phase of the day. Concentrations started to increase 2 h after dark onset and reached maximum levels after 4 h of darkness. The amplitude of the pineal melatonin rhythm increased considerably after 2 days and night-time concentrations in 20-day-old embryos were more than 5 times higher than in 18-day-old ones. Significant day/night differences in melatonin production were found both in pineals and eyes. Exposure of eggs to 1 h of light during the dark period decreased the high melatonin concentrations in the eyes but not in the pineals of the 20-day-old chick embryo. The results suggest that in this precocial bird at least part of the circadian system may already operate during embryonic life.     

Vasoactive intestinal peptide (VIP) occurs in nerves of the pineal gland

Summary Nerves staining with antibodies against vasoactive intestinal peptide (VIP) were detected in the pineal gland of the rabbit, cat and pig. VIP nerves were numerous in the cat but few in the rabbit and pig. A particularly rich VIP nerve supply was noted in the pineal stalk of the cat. The nerves were predominantly located around small blood vessels. Occasionally, nerve fibres were seen in the glandular parenchyma without obvious relation to blood vessels.Grant support from the Swedish Medical Research Council (04X-4499).     

Ethanol ingestive behavior as a function of central neurotransmission

Summary Uncontrollable alcohol ingestive behavior has been linked to deficits of central neurotransmission. The pineal gland plays an important role in modulating ethanol intake in numerous animal species. The opioidergic (i.e. -endorphin, enkephalin, and dynorphin) system is involved in both the actions of alcohol and opiates, as well as craving and/or genetic predisposition towards abuse of these two agents. Furthermore, there is significant evidence to link ingestive behaviors with the ventral tegmental accumbens-hypothalamic axis, whereby the biogenic amines dopamine and serotonin are reciprocally involved. Evidence is presented which implicates the striatum and the hypothalamus as possible specific loci for regional differences between alcohol-preferring and alcohol-nonpreferring mice. We believe that photoperiod-induced alcohol ingestive behavior may involve alterations in both pineal and hypothalamic opioid peptides.     

Development of melatonin rhythm in the pineal gland and eyes of chick embryo

A melatonin rhythm was observed in the pineals of 18-day-old chick embryos incubated under a light-dark regime of 186 h. A low pineal melatonin content was found during the light phase of the day. Concentrations started to increase 2 h after dark onset and reached maximum levels after 4 h of darkness. The amplitude of the pineal melatonin rhythm increased considerably after 2 days and night-time concentrations in 20-day-old embryos were more than 5 times higher than in 18-day-old ones. Significant day/night differences in melatonin production were found both in pineals and eyes. Exposure of eggs to 1 h of light during the dark period decreased the high melatonin concentrations in the eyes but not in the pineals of the 20-day-old chick embryo. The results suggest that in this precocial bird at least part of the circadian system may already operate during embryonic life.     

Vertebrate circadian rhythms: Retinal and extraretinal photoreception

Summary ERRs Both the pineal and the SCN are elements of the vertebrate multioscillator system although the relative importance of these 2 areas probably varies between, and possibly within, the different vertebrate classes. Extraretinal photoreception is a universal feature of submammalian vertebrates, and possibly of neonatal mammals, but is absent in adult mammals. Although the pineal systems of sumammalian vertebrates are photosensitive, the pineal system has been directly implicated as an extraocular site for the perception of entraining light cycles only in amphibians. In all other submammalian vertebrates extraretinal entrainment can occur in the absence of the pineal system although it is certainly conceivable that the pineal system may act as an alternate route of photoreception. These extraretinal-extrapineal receptors are located within the brain but the exact location(s) of these receptors within the brain is unknown. The hypothalamus would be likely area for this extraretinal photoreception, however, for several reasons: 1. Neurophysiological studies have identified light sensitive neurons in the frog's hypothalamus⁴³. 2. The avian hypothalamus is a site of photoperiodic photoreception^100–103. 3. The only other light sensitive structures known in vertebrates—the pineal system and the lateral eyes—are all derived embryologically from the hypothalamus. 4. The hypothalamus appears to be the site of a circadian clock and there may be advantages in having the photoreceptors and the clock anatomically close to one another. These considerations, of course, do not exclude the possibility that other brain areas may be involved as well. The reason behind the loss of extraretinal photoreception in mammals is uncertain. The shift to exclusive retinal photoreception in mammals may have been dictated by the extensive reorganization that occurred during the evolution of the mammalian brain. Or, perhaps, the increased size of the mammalian skull and overlying tissue made direct photoreception difficult and necessitated a shift to retinal photoreception. The persistence of extraretinal photoreceptors in submammalian vertebrates, however, underscores their importance in the sensory repertoire of vertebrates.     

The effect of luteineizing hormone on chicken testis and pineal gland uptake of 32P.

The glandular uptake of radioactive phosphorus (32P), administered carrier-free, was used as an endpoint for the study of the effects of luteinizing hormone (LH) on the testis and pineal gland of 3-, 10- and 13-day-old White Leghorn cockerels. Pineal uptake of 32P of the 13-day-old birds decreased and testis uptake of 32P increased following LH treatment. Maximum effects were observed when 20 mug LH was administered 4.0 h before autopsy. Although testis uptake of 32P increased following LH treatment in 3- and 10-day-old cockerels, pineal uptake of 32P remained unchanged.     

A lens-like specialization for photic input in the pineal window of an Indian catfish,Heteropneustes fossilis

Summary An unusual lens-like structure is reported in the pineal window of the Indian nocturnal catfishHeteropneustes fossilis. This is the first report of its kind for the pineal window of fishes. This structure, coupled with a pineal fossa and a pineal window, forms a specialization that apparently serves to concentrate the photic input to the intracranially situated pineal organ. This structure may play a significant role in the photoneuroendocrine function of the photosensitive pineal under conditions of low light intensity, controlling the fish's circadian rhythmic activities.The work was financially supported by CSIR, New Delhi (sanction No. 38(693)/88/EMR-II dated May, 1988) which is thankfully acknowledged.     

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.