Morphofunctional and molecular bases of pineal gland aging

The review analyzes the morphology, molecular and functional aspects of pineal gland (PG) aging and methods of its correction. The PG is the central organ that regulates the activity of the neuroimmunoendocrine, antioxidant and other systems of the body. Functional activity of the PG is decreased with aging, causing a decrease in the melatonin level. Molecular and morphological studies have demonstrated that the PG displays no pronounced atrophy with aging. Long-term experience has shown that epithalamine, a peptide extraction of PG, as well as epithalon, a synthetic tetrapeptide made on its basis, restore melatonin secretion in the PG and have a regulatory effect on the neuroimmunoendocrine and antioxidant systems of the body.     

Morphofunctional changes in the pineal gland during adaptation to hypothermia

The influence of hypothermal stress (+4 degrees during 3 h) on the ways of serotonin metabolism in pineal gland and its structure has been studied in dynamics on adult male Wistar rats. It has been revealed that melatonin-producing epiphyseal function suffers from phase changes in dynamics of adaptation--significant rising during 15 min. after beginning of the experiment, rehabilitation up to normal--in 30 min, and fast suppressing--in 3 hrs. Suppressing of the functional pineal activity is not due to switched serotonin metabolism with melatonin and new indoles release, but to a partial pinealocytes breaking from their active function.     

Biorhythms and pineal gland

Endocrine biorhythms are classified according to the period time, as one of the most characteristic properties of biorhythms. Each endocrine organ has parallel more than one biorhythms with different period time (e. g. circadian and circannual rhythms). The time of acrophase of the biorhythms at the different endocrine organs is fairly variant. This review summarizes the rhythmic function of the THS-thyroid, gonadotrophic-gonadal and ACTH-adrenocortical systems. Pineal gland plays an integrative role in the regulation of rhythmic function of the endocrine system. The melatonin secretion of this gland also reveals conspicuous circadian and circannual rhythms both in mammals and in birds. Mammalian pineal is functional only if its peripheral sympathetic innervation from the superior cervical ganglion is intact. In contrast, melatonin secretion and its circadian rhythm is also maintained in birds under isolated conditions (explanted into an in vitro superfusion system). The 24 hours period time of melatonin circadian rhythm can not be changed by light impulses. The phases of the circadian rhythm, however, can be turned by changing the time of environmental light-dark phases. The wavelength of the artificial light used for reversal of circadian rhythm is an important factor. The development of the entrainment and synchronization of the circadian melatonin rhythm in birds is independent of the rhythmic day-night changes in environmental lighting condition. The differences in the main elements of the biological clock between mammals and birds are discussed.     

松果体昼夜节律生物钟分子机制的研究进展

在各种非哺乳类脊椎动物中 ,松果体起着中枢昼夜节律振荡器的作用。近来 ,在鸟类松果体中相继发现了几种钟基因 ,如Per、Cry、Clock和Bmal等 ,其表达的时间变化规律与哺乳类视交叉上核 (SCN)的非常相似。钟的振荡由其自身调控反馈环路的转录和翻译组成 ,鸟类松果体和哺乳类SCN似乎具有共同的钟振荡基本分子构架 ;若干钟基因产物作为正向或负向调节子影响钟的振荡 ;昼夜性的控时机制同时也需要翻译后事件的参与。这些过程对钟振荡器的稳定性和 /或钟导引的光输入通路有着重要的调控作用     

The avian pineal gland

The pineal gland plays a key role in the control of the daily and seasonal rhythms in most vertebrate species. In mammals, rhythmic melatonin (MT) release from the pineal gland is controlled by the suprachiasmatic nucleus via the sympathetic nervous system. In most non-mammalian species, including birds, the pineal gland contains a self-sustained circadian oscillator and several input channels to synchronize the clock, including direct light sensitivity. Avian pineal glands maintain rhythmic activity for days under in vitro conditions. Several physical (light, temperature, and magnetic field) and biochemical (Vasoactive intestinal polypeptide (VIP), norepinephrine, PACAP, etc.) input channels, influencing release of melatonin are also functional in vitro, rendering the explanted avian pineal an excellent model to study the circadian biological clock. Using a perifusion system, we here report that the phase of the circadian melatonin rhythm of the explanted chicken pineal gland can be entrained easily to photoperiods whose length approximates 24 h, even if the light period is extremely short, i.e., 3L:21D. When the length of the photoperiod significantly differs from 24 h, the endogenous MT rhythm becomes distorted and does not follow the light-dark cycle. When explanted chicken pineal fragments were exposed to various drugs targeting specific components of intracellular signal transduction cascades, only those affecting the cAMP-protein kinase-A system modified the MT release temporarily without phase-shifting the rhythm in MT release. The potential role of cGMP remains to be investigated.     

The pineal gland of equatorial mammals

Summary The ultrastructure of the pinealocytes of the Malaysian rat (Rattus sabanus), a mammal inhabiting a zone near the equator where the annual variations of daylength are inconspicuous, was examined and compared with that of pinealocytes of other mammals.On the basis of the presence of granular vesicles, only one population of pinealocytes was found. A large number of granular vesicles and vesicle-crowned rodlets is characteristic of the pinealocytes of this equatorial species. Vesicle-crowned rodlets are especially numerous in the endings of the pinealocyte processes and; they most often found in direct topographical connection with the perivascular spaces.The physiological significance of the presence of such large amounts of vesicle-crowned rodlets and of the secretory process characterized by the formation of granular vesicles is discussed.

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Résumé Les pinéalocytes d'un Rat de Malaisie (Rattus sabanus), un animal vivant près de l'équateur donc dans une zone où les variations annuelles de la longueur des jours sont minimes, examinés au microscope électronique ont été comparés à ceux d'autres Mammifères. Une seule population de pinéalocytes a été observée. La présence d'un grand nombre de vésicules granulaires et de rubans circonscrits par des vésicules est la caractéristique premi`ere des pinéalocytes de cette espèce. Les rubans circonscrits par des vésicules ont été plus spécialement observés dans les terminaisons des prolongements des pinéalocytes où ils sont nombreux et la plus souvent en contact directe avec l'espace périvasculaire.L'importance physiologique de ces rubans circonscrits par des vésicules et des vésicules granulaires est discuté.

     

The pineal gland of nocturnal mammals

Summary In the pineal gland of the pipistrelle bat two different populations of pinealocytes and glial cells were observed electron microscopically. The pinealocytes of populations I and II differ in their content of metabolically active cell organelles. In the pinealocytes of population I, granular vesicles originating from the Golgi apparatus were found in the perikaryon and especially in the endings of the pinealocyte processes. Granular vesicles appeared to be more numerous in hibernating nulliparous females. The pinealocytes of population II are characterized by the presence of small cytoplasmic vacuoles, probably originating from cisternae of the granular endoplasmic reticulum and containing flocculent material of moderate electron density. The classification of the pinealocytes belonging to population II is discussed.This collaboration was initiated with the aid of an SRC European short visit grant to P.A.R.The study was supported by the Foundation for Medical Research, the Netherlands (FUNGO, 13-35-33)     

The pineal gland and seasonal reproductive adjustments

The pineal gland seems to play a major role in controlling and synchronizing circannual reproductive cycles in some mammals. The following scheme is based primarily on experimental evidence compiled using the golden hamster. However, it is probably applicable in one form or another to a number of long day breeding species. When hamsters are kept under natural photoperiodic conditions they exhibit a period of infertility followed by a period of fertility. The entire cycle encompasses approximately one year. The cycle has been divided into 4 distinctive phases: the inhibition phase, the sexually quiescent phase, the restoration phase, and the sexually active phase. During the inhibition phase the decreasing photoperiods in the fall of the year cause activation of the pineal gland and, as a consequence, gonadal regression. The sexually quiescent phase requires an intact pineal gland to maintain the gonads in a non-functional state. The restoration phase, which occurs in the spring of the year, allows the gonads to become recrudescent. This phase of the cycle seems to be light independent. The sexually active phase extends from spring until fall. During this phase the hypothalamo-pituitary-gonadal axis seems to be refractory to inhibition by the pineal gland. Some light is required during the summer months to interrupt the refractory period.     

The pineal gland and Rosenthal fibres.

115 pineal glands, collected from patients who died from various neurologic and visceral diseases, were studied. The Rosenthal fibres (RF) forming gliosis is consistently evident in the subependymal tissue around the gland, in the pineal recessus and in the intrapineal glial proliferation. In several instances the focal gliosis exhibited a central cystic degeneration. The RF-forming gliosis of the pineal gland appears independent of the basic diseases and of the process of atrophy and degeneration of the gland parenchyma. The embryonic development of the pineal gland could explain why the formation of RF may be considered a quasi-physiologic process of this region.     

The pineal gland and geographical distribution of animals

A detailed analysis of the occurrence of parietal eye component of the pineal complex in families of lizards has revealed that those in which the parietal eye is absent in most genera (e.g. Gekkonidae, Teiidae) tend to be restricted to low latitudes, whereas families in which the parietal eye is present in most of the genera (e.g. Agamidae, Iguanidae) extend to higher latitudes. Those few genera which lack parietal eyes in the families where the very great majority have parietal eyes are confined to ranges rather close to the equator. The parietal eye may be important in thermoregulatory or reproductive adaptations at higher latitudes where seasons are more severely varied than at lower latitudes. A pineal body is reported to be absent in crocodilians, edentates and, perhaps, dugongs. All these animals tend to inhabit tropical regions. In contrast, seals and walruses have remarkably large pineal glands and are found at very high latitudes. These few fragments of information cannot be used to support any conclusions, but they do suggest that it might be productive to consider the pineal complexes of animals in the context of their geographical distribution.Studies by the author supported by NIH grants NS-08554 and NS-12257.Presented during the Seventh International Biometeorological Congress, 17–23 August 1975, College Park, Maryland, USA.     

Annulate lamellae in hamster pineal gland

Pineal glands from young adult hamsters (Mesocricetus auratus Water-house) kept on a 14-10 light-dark photoperiod contain annulate lamellae. These annulate lamellae are apparently limited to the light pinealocytes. They are found in close proximity to nuclei, the Golgi apparatus, and agranular endoplasmic reticulum. There is also an interesting association or microtubules with the annulate lamellae. It seems reasonable that the presence of annulate lainellae in the pinealocytes may have some correlation with the physiological function or functions of these cells.     

Circadian rhythm of ornithine decarboxylase and its endogenous high molecular weight inhibitor in rat pineal gland]

The biochemical mechanisms involved in circadian variations of the activity of ornithine decarboxylase (EC 4.1.1.17)--the rate-limiting enzyme of polyamine biosynthesis in rat pineal gland were studied. The enzyme was separated from its endogenous high molecular weight inhibitor by gel-filtration of the cytosol fraction from this organ through Sephadex G-100 in the presence of 250 mM NaCl. The inhibitor was similar in its molecular weight (30 000) and activity to ornithine decarboxylase inhibior from rat liver. The amount of the enzyme in the pineal gland undergoes much smaller circadian variations as compared to that of the inhibitor. It is concluded that the circadian variations of the ornithine decarboxylase activity in the pineal gland may be largely due to the changes in the enzyme/inhibitor ratio.     

Vasopressinergic innervation of the pig pineal gland

An immunohistochemical study of the pineal gland of the domestic pig was carried out using the antisera raised against vasopressin (VP). The pineal glands were taken from the newborn, 21-day- and 7-month old female pigs. The pig pineal gland is moderately innervated by VP-immunoreactive nerve fibers. They run from the habenular commissure into the connective tissue septa and further into the pineal parenchyma. In the subependymal tissue as well as in the connective tissue septa, the fibers are smooth or with small varicosities and in the parenchyma with large ones. The obtained results point to extrapineal and extraepithalamic source of the fibers. The density of VP-immunoreactive fibers in the pineal gland of 7-month old pigs is higher than in the younger animals.