The multiple functions of the pineal gland have been collectively interpreted as constituting a general anti-stressogenic role. The adrenal glands play a central role in maintaining homeostasis. The major neuroendocrine consequence of long-term stress is elevated circulating glucocorticoid levels. In this study, the effect of chronic, oral hydrocortisone treatment on pineal biochemistry was investigated in male Wi star rats of the albino strain. The results show that seven days of oral hydrocortisone treatment endows the pineal gland with the ability to increase melatonin synthesis in organ culture. The increase is accompanied by a rise in NAT activity, cyclic AMP levels and enhanced specific binding to the pineal B-adrenergic receptors. It appears that hydrocortisone sensitizes the pineal gland to stimulation by B-adrenergic agonists. thus rendering the pineal more responsive to B-adrenergic agonists. Further studies were directed at demonstrating an anti-stressogenic function for the pineal gland by investigating whether the principal pineal indole, melatonin. could protect against the deleterious effects of elevated. circulating drocortisone levels. The results show that chronic, oral hydrocortisone treatment significantly increases liver tryptophan pyrrolase activity. The catabolism of tryptophan by tryptophan pyrrolase is an important determinant of tryptophan availability to the brain, and therefore, brain serotonin levels. The findings show that melatonin inhibits basal and hydrocortisone-stimulated liver tryptophan pyrrolase apoenzyme activity in a dose-dependent manner. This inhibition suggests that melatonin may protect against excessive loss of tryptophan from circulation and against deficiencies in the cerebral serotinergic system which are associated with mood and behavioural disorders. It was shown that another deleterious effect of chronic hydrocortisone treatment is a significant increase in the number of glutamate receptors in the forebrain of male Wistar rats. The increase in receptor number observed in this study is probably due to an increase in the synthesis of glutamate receptors and is associated with a marked reduction in the affinity of the glutamate receptors for glutamate. possible to demonstrate an receptor number or the For practical reasons, it was not effect of melatonin on either glutamate affinity of glutamate receptors for glutamate in rat forebrain membranes. In view of the neurotoxic effect of glutamate in the eNS, the functional significance of recently described glutamate receptors in the pineal gland was investigated. The results show that 10-4 M glutamate significantly inhibits the isoprenaline-stimulated synthesis of N-acetylserotonin and melatonin in organ culture when the pineal glands were pre-incubated with glutamate for 4 hours prior to stimulation with isoprenalin and when glutamate and isoprenaline were administered together in vitro. GABA, a glutamate metabolite could not mimic the decrease in isoprenalinestimulated melatonin, and it is likely that the observed effects were directly attributed to glutamate. Incubation of the pineal gland with 10-4 M glutamate in organ culture did not affect HIOMT activity in pineal homogenates, but significantly elevated both basal and isoprenaline-stimulated NAT activity. It was concluded that glutamate only inhibits melatonin synthesis in intact pineal glands and not in pineal homogenates. The present study has provided further support for an interaction between the pineal and the adrenal glands. There is an ever increasing likelihood that melatonin is an anti-stressogenic hormone and that the pineal gland may have a protective role to play in the pathology of stress-related diseases.

The pineal gland has become the subject of considerable investigation as it provides a productive experimental model for studying circadian rhythms and regulation of end organs. In the rat, the pineal gland provides a convenient model for investigating the noradrenergic receptor system and the effects of various drugs on this system. The effect of appetite suppressants on the rat pineal gland function is described. Appetite suppressants increase melatonin synthesis in organ cultures of rat pineal glands. This effect appears to be mediated by noradrenaline acting on β-adrenoceptors on the pinealocyte membrane. When β-adrenoceptors are blocked, the appetite suppressant-induced rise in melatonin synthesis is prevented. Depletion of noradrenaline in sympathetic nerve terminals also prevented the appetite suppressant-induced rise in melatonin synthesis. Activation of β-adrenoceptors is followed by a rise in N-acetyltransferase activity via a cyclic adenosine monophosphate second messenger system. The effect of appetite suppressants on the activity of liver tryptophan pyrrolase was also investigated. The activity of this enzyme is an important determinant of tryptophan availability to the brain and consequently of brain serotonin levels. The results show that appetite suppressants inhibit both holoenzyme and total enzyme activities of tryptophan pyrrolase. This finding suggests that appetite suppressants may act by inhibiting tryptophan pyrrolase activity thereby increasing brain serotonin, a phenomenon known to be associated with anorexia. There are two possible mechanisms by which appetite suppressants inhibit tryptophan pyrrolase activity. Firstly, these agents, being drugs of dependence, may increase liver NADPH concentrations which inhibit pyrrolase activity. Secondly, appetite suppressants may act on the pineal gland to stimulate melatonin synthesis. Melatonin inhibits pyrrolase activity in a dose-dependent manner. This inhibition will elevate plasma tryptophan levels which result in a rise in brain serotonin synthesis. The present study suggests a possible relationship between the pineal gland and appetite centres in the hypothalamus. Melatonin may have a direct effect on appetite centres since food restriction is associated with an increased melatonin binding in the hypothalamus. If this possible relationship can be extended, melatonin can open new possibilities for the control of food intake and consequently, of pathological obesity.

No description available.

O objetivo geral da presente tese é testar a hipótese que a pineal faz parte integrante da resposta ao estresse, da mesma forma que está integrada ao processo inflamatório. Dois modelos de estresse, contenção e frio, foram aplicados aos ratos por 30 min ou 2 horas. Os resultados foram: ausência de úlceras gástricas e TNF em nível sérico por ambos os estresses, apenas aumento de corticosterona; somente em duas horas qualquer um dos estresses aumentou significativamente melatonina da pineal; tratamento tanto com metirapona como com mifepristone aboliram indistintamente os efeitos dos estresses; tratamento tanto com talidomida como com fenilefrina não modificaram os efeitos dos estresses. Concluímos que, o estresse moderado agudo, pela ação da corticosterona, promove modulação da pineal na dependência do estado fisiológico da mesma. Confirmamos a existência de uma relação entre as glândulas adrenais e pineal. Afirmamos que a glândula pineal exerce, além de suas clássicas funções cronobióticas, um papel de grande sensor do estado geral ao organismo inteiro. / The objective of this thesis is to test the hypothesis that the pineal is a player on stress response, likewise that it is one player in inflammatory process. Two stress models, restraint and cold, were applied to the rats for 30 min or 2 hous. The results were: absence of gastric ulcers and TNF serum levels in both stresses, just enhancement of corticosterone plasma levels; only in two hours anyone stress increased significantly pineal melatonin; metyrapone or mifepristone treatment abolish indistinctly the effects of the stresses; thalidomide or phenylephrine treatment did not modify the effects of the stresses. We conclude that the acute moderate stress by the corticosterone action promote modulation of pineal on the dependence of the physiological status of itself. We confirm the existence of a network between the adrenal and pineal glands. We affirm that the pineal gland performs, beyond of its chronobiotical classical functions, one role of the great sensor of internal body state to the whole organism.

O metabolismo energético é dependente, dentre outros fatores, de uma temporização circadiana entre os tecidos participantes da regulação metabólica. O processo de sincronização parece depender da expressão dos genes relógio e de mediadores como a melatonina, que associam o oscilador central e os osciladores periféricos. Investigamos o papel da melatonina na expressão dos genes relógio em tecidos periféricos, onde ratos Wistar foram divididos em dois grupos: pinealectomizados e controle. Após 45 dias os animais foram sacrificados circadianamente e seus tecidos de interesse extraídos para análise através do PCR convencional. A pinealectomia ocasionou significativa desorganização temporal na expressão de quase todos os genes relógios dos tecidos muscular e do adiposo periepididimal. O tecido hepático foi o que menos sofreu alterações pela pinealectomia. Em conclusão, esses dados mostram que a melatonina é necessária para manutenção da ritmicidade dos genes relógio no tecido muscular estriado esquelético, no tecido adiposo periepididimal e no tecido hepático. / The energy metabolism is dependent, between other factors, of a circadian timing among the tissues participants of the metabolic regulation. The synchronization process appears to depend on the expression of clock genes and mediators such as melatonin, involving the central oscillator and peripheral oscillators. We have investigated the role of melatonin in the expression of clock genes in peripheral tissues. Rats have been divided into two groups: pinealectomized and control rats. After 45 days the animals were sacrificed and their tissues of interest have been extracted for analysis by conventional PCR. Pinealectomy caused a significant disruption in the temporal expression of almost all genes of muscle tissue and fat tissue. The liver tissue was the least affected by changes of pinealectomy. In conclusion, these data show that melatonin is necessary for maintaining the rhythmicity of clock genes in skeletal muscle, adipose tissue and liver tissue.

by Louisa Li-Ha Lo. / Bibliography: leaves 174-182 / Thesis (M.Ph.)--Chinese University of Hong Kong, 1986

The morphological and physiological effects of pineal gland activity on the prolactin-secreting cells of the anterior pituitary were examined in blind-anosmic male and female rats. Prolactin synthesis was measured by the ability of anterior pituitaries to incorporate ³H-leucine into prolactin in vitro. Pituitary storage of prolactin was assessed by measuring radioimmunoassayable prolactin levels in the pituitaries in vivo and the total amount of immunoassayable prolactin in vitro. The effects of the activated pineal on prolactin release were estimated by monitoring radioimmunoassayable serum prolactin levels. Finally, the morphology of the prolactin cells was analyzed by both light microscopic immunocytochemistry and transmission electron microscopy. Eight weeks after blinding and olfactory bulbectomy in prepubertal male and female rats, prolactin synthesis, storage and release were all significantly decreased compared to unoperated control values. Pinealectomy in blind-anosmic rats completely prevented these effects. Similar results were obtained four weeks after treatment, but not after only one week. Furthermore, the reductions in prolactin synthesis, storage and release were not a consequence of the pineal-induced gonadal atrophy in these animals, since these effects persisted in ovariectomized-blind-anosimic rats. The pineal also elicited these effects in female rats rendered blind-anosmic after puberty, though to a lesser degree than when immature animals were used. Concomitant with these alterations in prolactin synthesis, storage and release were regressive changes in the morphology of individual prolactin cells and in the number of these cells in the pituitary. Anterior pituitaries from blind-anosmic rats were approximately half the weight of glands from intact animals and contained a third less DNA. This loss of cell number was largely accounted for by a reduction in the number of prolactin cells, as shown by immunocytochemistry. Additionally, each prolactin cell was smaller in size in blind-anosmic female rats and showed scant endoplasmic reticulum, a small Golgi complex, few secretory granules and rare exocytosis patterns. From these data I conclude that the pineal gland exerts a strong inhibition on the prolactin cells of blind-anosmic rats.

No description available.

Thesis (Ph. D.)--Illinois State University, 1972. / Title from title page screen, viewed Sept. 23, 2004. Dissertation Committee: Mathew J. Nadakavukaren, John L. Frehn (co-chairs), Herman Brockman, Arthur Merrick, Joseph Tsang. Includes bibliographical references (leaves 139-148) and abstract. Also available in print.

Thesis (M.S.)--University of Wisconsin--Madison, 1971. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.