Showing papers on "Pinealocyte published in 1981"

Melatonin. A Mammalian Pineal Hormone

Abstract: PROBABLY no other organ in the body has suffered so long from a lack of its true functional recognition as the pineal gland. For more than two centuries the pineal was thought to be the seat of the soul or a vestigial remnant of the parietal eye. However, pineal research over the last 20 years has contributed significantly to unraveling the functional significance of this enigmatic endocrine gland. In this respect the isolation and characterization of melatonin by Lerner et al. (1) in 1958 constituted a landmark inasmuch as it was the first substance to be characterized in the pineal gland that reproduced many of the effects of pineal extracts or reversed the endocrine sequelae of pinealectomy. Today the pineal gland is recognized as an active functioning neuroendocrine organ that responds primarily to photic stimuli (and secondarily to hormonal signals originating in target tissues), exhibits circadian rhythms, and influences the metabolic activity of a host of endocrine glands.

Immunohistochemical evidence for the presence of melatonin in the pineal gland, the retina and the Harderian gland.

Abstract: The presence of melatonin is demonstrated in the pineal gland, the retina and the Harderian gland in some mammalian and non-mammalian vertebrates, using a specific fluorescence labelled antibody technique. Four different potent antibodies against melatonin have been used and compared. In the pineal gland of hamsters, mice, rats and snakes, specific fluorescence, mostly restricted to the cytoplasm of the cells, is detected in pinealocytes. Fluorescence is also detected in the pineal organ of fishes, tortoises and lizards, but it has not been possible, from cryostat sections of fresh tissue, to assert which kind of cell is reacting (photoreceptor cells or interstitial ependymal cells). In the retina, fluorescence is almost exclusively restricted to the outer nuclear layer. In the Harderian gland of mammals and reptiles, fluorescence is localized in the secretory cells of the alveoli and mostly restricted to the cytoplasm surrounding the nucleus. These results are discussed in relation to the concept of melatonin synthesis at extrapineal sites independent of pineal production.

Melatonin Production by Extra-pineal Tissues

Abstract: Hydroxyindole-O-methyltransferase (HIOMT), which catalyzes the O-methylation of N-acetylserotonin to melatonin, is not confined to pineal glands, as was thought when the enzyme was first described in 1960. Five years later it was noted that HIOMT is present in the brain and eyes of anuran amphibians, fishes, reptiles and birds. Indeed, in anurans, HIOMT in the retina has far greater activity than in the pineal body. Whereas HIOMT can be detected in the retina of fetal rats, not until a few days after birth can it be demonstrated in the pineal gland. In the mole there is two to ten times more HIOMT activity in the eyes than in the pineal gland. The HIOMT in the retina and pineal gland appear to have similar properties. There is also an HIOMT in the Harderian glands of rats, but it has biochemical characteristics that differ from retinal and pineal HIOMT. N-Acetyltransferase (NAT), which converts serotonin to N-acetylserotonin is found not only in the pineal gland but also in the retina of chickens, sparrows and rats. Furthermore, NAT activity varies diurnally like the enzyme of the pineal gland, being higher during the dark phase than during light. Melatonin has been localized by bioassay and immunohistochemical technique to several regions of the brain and the retina of chickens and rats, the retina of trout, the Harderian gland of rats, and the gut of humans, rats and rabbits. The evidence is quite convincing that all these organs synthesize melatonin and do not acquire it totally from the pineal gland via the blood. Indeed, following pinealectomy, melatonin can still be detected in the serum of rats. Melatonin is also present in the brain of rats, the eyes of chickens and trout, and in the blood of trout, mice and sheep after the pineal gland has been ablated. It is evident that melatonin is not a unique or exclusive product of pineal glands. Melatonin is synthesized by and released from a number of tissues. It seems possible that the cells which produce melatonin are within the widely-dispersed APUD system.

Neonatal Rat Pinealocytes: Typical and Atypical Characteristics of [125I]Iodohydroxybenzylpindolol Binding and Adenosine 3′5′-Monophosphate Accumulation

Abstract: Techniques are described which make it possible to studyβ-adrenergic receptors on intact neuroendocrine cells. Receptors were characterized on neonatal pinealocytes using the radioligand [125I]iodohydroxybenzylpindolol ([125I]IHYP). Specific binding of [I25I]IHYP, which is 4-fold greater than nonspecific binding, is concentration and temperature dependent, reversible, and saturable. [125I]IHYP binds noncooperatively (Kd = 35 PM), and Scatchard analysis indicates that only a single class of receptor sites for [125I]IHYP is present. Under the conditions used, it appears that there are about 12,000 ± 1,100 sites/cell. Inhibition of specific [125I]IHYP binding by β-adrenergic agonists and antagonists is stereospecific, and the relative potency of agonists is characteristic of binding to β-adrenergic receptors. Analysis of adrenergic stimulation of intracellular cAMP accumulation indicates that similar half-maximal concentrations of antagonists inhibit [125I]IHYP binding and adrenergically stimulated cAMP accu...

Time-related changes in size of nuclei of pinealocytes in rats.

Abstract: In a study of 96 adult male Sprague-Dawley rats, da-and time-related changes of the mean nuclear volume of pinealocytes were determined with the aim of testing the reproducibility of the karyometric findings described by Quay and Renzoni (1966). It is shown (i) that statistically significant differences exist between the central and peripheral mean volumes of pinealocyte nuclei/group of animals and time point (p<0.001), (ii) that the day and time related differences are statistically different in both regions (p<0.001), (iii) that in the center and periphery of the pineal body different diurnal patterns exist, and (iv) that the diurnal patterns are not parallel in the two regions. The question discussed is (i) whether or not probable superimposed infradian rhythms may account for the different diurnal patterns, and (ii) whether these patterns in the two regions indicate functional differences between the “cortex” and the “medulla” of the rat pineal body.

Circadian changes in microtubules, synaptic ribbons and synaptic ribbon fields in the pinealocytes of the baboon (Papio ursinus).

Abstract: In baboons kept under controlled lighting conditions, microtubules (MT) are readily seen in the perikaryal cytoplasm and in the perivascular processes of pinealocytes. A significant increase in the number of MT, single synaptic ribbons (SR) and the formation of synaptic ribbon fields (RF, i.e. organelles which consist of multiple dense rodlets or plates, and vesicles), occur during the dark phase of a circadian light-dark cycle. MT may act as “tracks” for the oriented flow of vesicles derived from the smooth endoplasmic reticulum, to cytoplasmic sites where RF are being formed. The origin of the dense rodlets of RF remains unknown. Structural differences between SR and RF indicate that the latter organelles are not directly involved in impulse propagation between adjacent baboon pinealocytes. RF may function as storage organelles for some of the pineal secretory products which are formed in large amounts during the dark phase.

Physiologic Regulation of Melatonin

Abstract: The concentration of melatonin shows a marked diurnal rhythm in the pineal gland and in blood with high levels normally occurring during dark and low levels during light. Synthesis in the pineal gland is controlled by a noradrenergic mechanism regulated by an indirect neural pathway from the eye. The pineal enzymes N-acetyltransferase and hydroxyindole-O-methyltransferase are activated when noradrenaline is released during darkness resulting in synthesis and release of melatonin. Hydroxyindole-O-methyltransferase has also been identified in the retina, Harderian gland and gut. We have demonstrated melatonin in these structures. Melatonin has also been localized in the optic chiasm, suprachiasmatic nucleus and in the palatine salivary gland but it is not known whether it is synthesized in these locations or whether extrapineal melatonin enters the circulation. In both diurnal and nocturnal species melatonin in circulation shows peak levels in the dark and low levels in the light. There is evidence for an endogenous rhythm generator responsible for synchronizing rhythms including the melatonin rhythm at approximately a 24 hour interval which can be cued by light. The onset of light rather than the onset of darkness appears to act as the cue or Zeitgeber. If the hamster or rat is exposed to 1½ or 2 hours of light in the 24 hour day, pineal and serum melatonin rhythms are synchronized in phase with light onset rather than onset of darkness. The melatonin rhythm can be dissociated from the adrenal rhythm. Restricting feeding to early hours of light in the rat will cause a shift in the corticosterone rhythm without altering the rhythm in plasma or pineal melatonin. Increasing the length of darkness does not necessarily produce a longer peak of melatonin in blood. In the hamster or rat, exposed to a shortened photoperiod with only 1½ or 2 hours of light per day both the pineal and serum melatonin rhythms are generally unchanged. There appears to be feedback regulation of circulating melatonin. In rats immunized against melatonin to cause a lowering of circulating melatonin, pineal content is increased. High affinity binding of melatonin to brain cytosol and membrane as well as to testicular and ovarian cytosol has been described and may be indicative of receptors through which melatonin produces its central and peripheral effects. We have found cytosol binding in a variety of human, bovine and rat brain regions with an affinity approximately three times that of the reported membrane binding. Melatonin binding has also been defined by immunofluorescence in the pineal gland. This binding has a diurnal rhythm differing from that of melatonin and has an affinity constant in the nanomolar range.

Some functional aspects of the ultrastructure of rat pinealocytes.

Abstract: An analysis of more than 75000 electron micrographs from 84 intact control and 167 experimental male rats divided into 11 groups subjected to various treatments, was performed in the present study, a special attention being paid to the relation of cytoplasmic organelles to the processes of synthesis and secretion of pinealocytes. From these observations the following conclusions have been drawn: 1. specific pineal cells - the pinealocytes - show several attributes of metabolically active endocrine cells; 2. at least two probably intimately related secretory processes are present in the rat pinealocytes; 3. several cytoplasmic structures may be involved in the secretory mechanism of the rat pinealocytes.

Gap junctions between pinealocytes. A freeze-fracture study of the pineal gland in rats.

Abstract: The intercellular junctions between the pinealocytes of male rats were investigated by freeze-fracture and conventional electron microscopy. Our findings reveal that the intercellular contacts between pineal cells, formerly described as zonulae adhaerentes or zonulae occludentes, are in fact gap junctions which are difficult to characterize in thin sections due to their peculiar geometrical arrangement, which is in the form of “fenestrated” communicating zonules. The arrangement of these communicating zonules around rudimentary lumina of pineal clusters and rare transitions between tight and gap junctions may point to phylogenetic transformations of occluding into communicating zonules, corresponding with the change of the pineal gland from a sensory to a secretory organ. Alternatively, these tight-to-gap junctional transitions may reflect the periodic (circadian or seasonal) activity of the pineal gland.

Modes of protein and peptide uptake in the pineal gland of the Mongolian gerbil: an ultrastructural study.

Abstract: The possible existence of either a blood-brain barrier or a CSF-brain barrier was examined in the pineal gland of the Mongolian gerbil using the ultrastructural tracers, horseradish peroxidase (HRP) and microperoxidase (MP). The mechanism of protein and peptide transport within the pineal gland and its possible relationship to pineal concretions was also considered. Gerbils were injected with either MP or HRP intravenously (IV), or they received intraventricular (IVT) injections of HRP. The IV injections resulted in both MP and HRP movement through the endothelial cells of the gland by vesicular transport and by diffusion through the endothelial cells of the gland by vesicular transport and by diffusion through the endothelial intercellular junctions. Following the IVT injections, the tracer was demonstrated in the subarachnoid space as well as in the glial cells associated with the periphery of the gland. In addition, after the IVT injections, rounded enlargements of the intercellular space that resembled canaliculi were filled with reaction product. In both cases (IVT and IV), the reaction product was localized to the perivascular space, to the glial cells and pinealocytes, and to the intercellular spaces. More importantly, there was specific localization of the tracers in the vacuolated pinealocytes and in the pineal concretions. The results of this study demonstrate several significant findings: 1) neither a blood-brain barrier nor a CSF-brain barrier exists in the pineal gland of the gerbil, 2) localization of the tracers in pineal concretions indicates a relationship between these structures and protein and peptide storage within the gland, and 3) the presence of the tracers within canaliculi after the IVT injections suggests a possible mode of secretion of pineal substances into the CSF.

Melatonin: Origin, Control of Circadian Rhythm and Site of Action

Abstract: It has been postulated that melatonin could be secreted directly into the CSF as well as into the blood. Is the CSF route of secretion important? The pineal is a major source of circulating melatonin. Does circulating melatonin also originate from other structures? The alternating 24-hour light/dark cycle serves as the zeitgeber for the melatonin rhythm. What event is the cue? Does increasing the hours of darkness lead to enhanced melatonin release? What is the relation of the pineal circadian rhythm to other rhythmic phenomena including rhythms in other hormones, in temperature and in locomotion? Both membrane and cytosol binding of melatonin have been described. Which type of binding is most likely to represent the physiologic receptor?

The pineal gland of nocturnal mammals. II. The ultrastructure of the pineal gland in the pipistrelle bat (Pipistrellus pipistrellus L.): presence of two populations of pinealocytes.

Abstract: 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

Effects of changes in calcium concentration on basal and stimulated 32P incorporation into phospholipids in rat pineal cells.

Abstract: The Ca2+ requirement for alpha-agonist stimulation of 32P incorporation into acidic phospholipids (the phosphatidylinositol effect) of dispersed pineal cells was evaluated by means of several different compounds that interfere with Ca2+ disposition. Simple omission of Ca2+ led to slight increases in basal and norepinephrine-stimulated phosphatidyl-CMP (CDP-diacylglycerol) and phosphatidylglycerol labeling without affecting phosphatidylinositol labeling. In the absence of Ca2+, EGTA (200 microM) or the ionophore for divalent cations A23187 (10 microM) elicited large increases in phosphatidic acid, phosphatidyl-CMP, and phosphatidylglycerol labeling while strongly inhibiting the phosphatidylinositol effect. The Ca2+ translocation inhibitor LaCl3 also reduced the magnitude of this effect. The phosphatidylinositol effect is, however, not induced by increased Ca2+ entry into the cytosol, since A23187 did not mimic the effect of norepinephrine. Under conditions where membrane Ca2+ was lowered, the addition of 1 mM-inositol greatly reduced phosphatidic acid, phosphatidylglycerol, and phosphatidyl-CMP labeling with concomitant increases in basal and norepinephrine-stimulated phosphatidylinositol labeling approaching that observed in the presence of norepinephrine and 2.5 mM-Ca2+. In the presence of 2.5 mM-Ca2+, inositol had negligible effects on phosphatidylinositol labeling. It was concluded that changes in membrane Ca2+ availability and/or disposition alter phospholipid metabolism and concurrently reduce the magnitude of the phosphatidylinositol effect, perhaps by making the pool of readily available inositol in pinealocytes rate-limiting.

Circadian Rhythmicity in the Activity of HIOMT in the Formation of Melatonin and of 5-Methoxytryptophol in the Retina, Harderian Gland and Pineal of the Male Hamster

Abstract: The day and night rhythms in the activity of HIOMT in the formation of melatonin and of 5-raethoxytryptophol have been determined in the retina, Harderian gland and pineal of adult male golden hamster. It appears that (1) with the exception of the end of the dark period, the extra-pineal synthesis of melatonin and 5-methoxytryptophol is always higher than that in the pineal; (2) the circadian synthesis of methoxyindoles is different in each organ, and (3) in the pineal the circadian activity of HIOMT involved in 5-methoxytryptophol formation is different from that of the enzyme involved in the formation of melatonin.

Topographical relationships of synaptic ribbons in the pineal system of the vole (Microtus agrestis).

Abstract: In the pineal system of the vole (Microtus agrestis) both the superficial and the deep pineal exhibit a high percentage of synaptic ribbons lying in intimate contact with the cell membrane of the pinealocytes. At the sites of contact, densities resembling the presynaptic dense projections of synapses are arranged between the ribbons and the cell membrane. Opposite the sites of contact various elements were found. The quantitative estimation revealed that in the superficial pineal about 40% and in the deep pineal about 60% of the membrane-contacting ribbons are located opposite glial cells: in both organ parts about 18% of the membrane-contacting ribbons were found opposite adjacent pinealocytes. The location of ribbons at the perivascular space was almost exclusively found in the superficial pineal, while the cerebrospinal fluid-contacting area in the deep pineal exhibited ribbons in intimate contact with the lumen of the third ventricle. The heterogeneity of the topographical relationships would seem to indicate a diffuse functional effect of the synaptic ribbons in the mammalian pineal gland.

Morphologic development of neonatal rat pinealocytes in monolayer culture.

Abstract: The morphological development of pinealocytes maintained in monolayer culture, without the neural and humoral effects present in the developing rat has been studied and compared with the development that occurs in vivo. Pinealocytes in 5 day cultures contained organelles that were similar to those present in the pineals of intact 5 day old rats. However, light and dark cells were not noted in culture, and the cultured cells did not have the dense granules noted in vivo. As pinealocytes developed in culture, cytoplasmic processes increased in length and number. By 21 days of culture age, synaptic ribbons were found to have decreased in number, the difference between light cell and dark cell cytoplasm had become more prominent, and dense-cored vesicles had become more numerous, just as in the developing gland in vivo. These results suggest that the complex neural and humoral factors impinging upon the developing neonatal pineal in the intact animal may not be necessary for some aspects of its ultrastructural differentiation.

Pineal Cells in Monolayer Culture

Abstract: Publisher Summary This chapter examines the pineal cells present in monolayer cultures. Pineal cells play an important role in reproductive physiology. The morphology of the cells in pineal monolayer cultures resembles that found in organ expiant culture and that found in vivo as well. The fact that the pinealocytes attach to a layer of fibroblast-like supporting cells is typical of many types of primary cell culture. The pinealocytes themselves contain synaptic ribbons and cilia with the 9 + 0 microtubule arrangement, and these ultrastructural markers are relatively specific for pineal cells. In addition to this, they demonstrate a cellular surface studded with microvilli. These structures are probably responsible for the complex intertwining of cellular processes seen on scanning electron microscopy. Finally, the quality of staining of the pinealocyte ground substance was shown to vary with changes in the extracellular environment bathing the cells. In studies discussed in the chapter, it was observed that pineal cells may have both α- and s-adrenergic receptors that can stimulate NAT activity. The cultures used in such studies were seen to undergo both ultrastructural and pharmacologie changes with the development in culture. The lengthening of cellular processes and relative decrease in the prevalence of synaptic ribbons are characteristic changes that occur as the pineal develops in vivo.

A Light and Electron Microscopic Study of the Pineal Body of the Nutria (Myocastor Coypus)

Abstract: Light and electron microscopic studies of the nutria ( Myocastor coypus ) pineal gland revealed pinealocytes interspersed among glial, vascular, and neuronal elements. Each pinealocyt

The Effects of Microelectrophoretically Applied Melatonin, Putative Transmitters, Thyroxine and Sex Hormones on the Electrical Activity of Pineal Cells in the Guinea-pig

Abstract: The effects of microelectrophoretic application of melatonin, noradrenaline, acetylcholine, thyroxine, testosterone and oestrone on pineal cell electrical activity were evaluated. With the exception of acetylcholine and oestrone pineal cells showed a circadian rhythm in sensitivity to the application of the substances. It is apparent from these studies, that (1) transmitters and hormones can bring about direct changes in the firing frequency of pineal cells, (2) all pineal cells do not respond to these substances in the same way and (3) that melatonin either produced in the pineal organ or reaching the gland via the general circulation may be capable of directly influencing the cells engaged in its own synthesis or in the synthesis of other pineal antigonadotropins.

Melatonin Receptors in Pineal

Abstract: Melatonin coupled to a binding material has been identified in the pineal gland of the rat using a semi-quantitative immunohistological procedure. Bound melatonin has a daily pattern markedly different from melatonin determined by radioimmunoassay, with low levels early in the light, increasing through the day to a maximum in the early dark. This change is suppressed by acute melatonin or vehicle injection, regardless of when during the day the injections are given. The functional properties of this binding substance are unknown.

Cytological Aspects of Indoleamine Secretion in the Pineal Gland

Abstract: The present review, based upon numerous reports published during the last ten years, attempts to clarify some cytological aspects of the indoleamine secretory process in the pineal. Because only a small part of the serotonin can be engaged in the formation of melatonin, serotonin and 5-methoxyindoles have been separately considered. By combined fluorescence histochemical, radioautographic and ultracytochemical data obtained in normal and drug-treated animals, it has been shown that anabolism, catabolism and storage of serotonin takes place in pineal cells belonging to the sensory cell line (photoreceptor cells, secretory rudimentary photoreceptor cells or pinealocytes). The role of the “glial” cells in indole metabolism is not evident. Although they are probably cells of the sensory line, the scarcity of reports concerned directly with melatonin has made it impossible to identify with certainty the cells implicated in its storage. The concept of melatonin as a pineal hormone is discussed.

Melatonin and Other Pineal Products

Abstract: Morphological studies on the mammalian pinealocyte predict the secretion of proteins, peptides or related substances. Certain pineal activities have been reported which cannot be accounted for on the basis of the physiological action of melatonin. These facts have led investigators to search for non-indolic pineal substances which may carry out an important role in neuroendocrine regulation. Abundant evidence has accumulated showing that melatonin-free fractions derived from extracts of pineal tissue demonstrate significant inhibitory effects on gonadotropin and the reproductive system. Additionally, recent experiments in light-deprived hamsters have shown that when stimulated the pineal gland can evoke reduced pituitary and serum prolactin levels. These results have led to the search for and discovery of pineal prolactin inhibiting factors (PPIF). Rat and bovine PPIF, partially purified from acetic acid extracts using Sephadex chromatography, Amicon ultrafiltration and high performance liquid chromatography (HPLC), was observed to reduce acutely serum prolactin levels in rats, an effect not shared by melatonin. Newly identified pineal compounds include pteridines, which may act as co-factors in the regulation of catecholamine and hydroxyindole synthesis, the antigonadotropic tripeptide threonylseryllysine, and the aminosulfonic acid taurine which has been shown to be synthesized by the rat pineal and to stimulate pineal N-acetyltransferase activity and melatonin synthesis. Finally, a bovine pineal substance showing neurohypophysial hormone-like activity was partially purified from glacial acetic acid extracts by Sephadex chromatography, Amicon ultrafiltration and ion exchange chromatography. The elution volume of this substance, detected by milk ejection bioassay, was not identical to that of synthetic arginine vasotocin or arginine vasopressin, but showed chemical characteristics more closely related to oxytocin or a substance of unknown structure.

Melatonin in Non-endocrinological Pathology

Abstract: Short, general review on melatonin in non-endocrinological pathology is made excluding the matters on neuro-psychiatric conditions which have been touched in the previous lecture of this session. Besides, the result of our study on synaptic ribbons of the pinealocytes is introduced, and its possible usefulness as a morphological marker for melatonin secretion is discussed, referring to a good correlation between our result and that of biochemical parameter obtained by other researchers. Finally, another result of our morphological study on the relation between pineal weight and adrenal cortex thickness is shown, and a possible role of the pineal gland, including melatonin secretion, in the general adaptation syndrome is explained, which would be the matter much more than mere endocrinology in pathology.

Ontogenic and Phylogenic Aspects of the Circadian Rhythm of Melatonin Synthesis in the Pineal Gland

Abstract: The circadian rhythm of melatonin synthesis in the pineal glands is regulated by the change of serotonin N-acetyltransferase activity. The present report deals with the following aspects of the circadian rhythm of N-acetyltransferase activity: (i) Ontogenesis of the N-acetyltransferase rhythm in the pineals of rats raised under various lighting conditions. (ii) The change of N-acetyltransferase activity under an ultradian lighting schedule. (iii) The neural regulation of N-acetyltransferase rhythm in the pineals of immature rats. (iv) The circadian rhythmicity and photosensitivity of chicken pineal gland in culture.

Effect of castration and adrenalectomy on the ultrastructure of pinealocytes in the female garden dormouse (Eliomys quercinus L.) under different conditions of lighting and temperature during the normal period of hibernation

Abstract: The ultrastructure of the female garden dormouse pinealocyte has been studied during the period of hibernation in normal, castrated, castrated and adrenalectomized hibernant animals and non-hibernant ones living under a L-D=10–14 photoperiodicity or continuous lighting. Continuous illumination on the one hand, and gonad and adrenalectomy on the other, have similar effects on the ultrastructure of pinealocytes. Especially a striking reduction of liposomes, an increased development of the Golgi apparatus and of cisterns formed by the rough endoplasmic reticulum were observed. The observations suggest that the liposomes are involved in a perhaps indoleaminergic antigonadotropic secretory process whereas the peculiar dilated cisterns of the rough endoplasmic reticulum may be related with a pineal polypeptidergic gonadotropic secretory process.