The interaction of the thyroid gland, pineal gland and immune system in chicken

The interaction of immunological system, thyroid and pineal gland was studied in 5-week old males of Gallus domesticus. Several morphometrical parameters in pineal and thyroid glands were measured after bird immunization with human red blood cells and/or treatment with melatonin or seduxen, melatonin receptor blocker. The peak of the thyroid activity was found on Day 7 after immunization. The immune system appears to directly activate the thyroid gland only in the presence of certain level of melatonin. We suggest that the melatonin mechanism of action includes the enhancement of thyroid gland sensitivity to immune factors. Seduxen prevented the stimulatory influence of the immune system on the thyroid gland.     

Changes in rodent thyroid hormones and cyclic-AMP following treatment with pineal indolic compounds.

Treatment of rats with pineal indolic compounds 5-methoxytryptophol, 5-hydroxytryptophol and serotonin brought about a significant increase in serum thyroxine levels, while serotonin and melatonin caused an increase in thyroid cAMP content with corresponding decrease in the gland's hormones. The total quantity of cAMP in the thyroid was also increased by melatonin in the organ culture system. All these findings would indicate that some of the pineal indoleamines elicit a direct action on the thyroid by stimulating the adenyl cyclase activity and intrathyroidal cAMP, bringing about increased release of thyroxine into the blood stream, and that this is usually not accompanied by adequate synthesis in the gland. Our observation that continuous darkness, which stimulates pineal activity, also brought about an increase in cAMP, concours with our finding of a stimulatory effect of the indolic compounds on thyroid hormone release.     

The role of oxidative stress in physiological and pathological processes in the thyroid gland; possible involvement in pineal-thyroid interactions

Reactive oxygen species (ROS) play an important role in physiological processes, but - when being in excess - ROS cause oxidative damage to molecules. Under physiological conditions, the production and detoxification of ROS are more-or-less balanced. Also in the thyroid, ROS and free radicals participate in physiological and pathological processes in the gland. For example, hydrogen peroxide (H2O2) is crucial for thyroid hormone biosynthesis, acting at different steps of the process. Additionally, H2O2 is believed to participate in the Wolff-Chaikoff's effect, undergoing in conditions of iodide excess in the thyroid. Much evidence has been accumulated indicating that oxidative stress is involved in pathomechanism of thyroid disease, e.g., Graves' disease, goiter formation or thyroid cancer. Melatonin (N-acetyl-5-methoxytryptamine) - the main secretory product of the pineal gland - is a well-known antioxidant and free radical scavenger, widely distributed in the organism. Mutual relationships between the pineal gland and the thyroid have - for a long time - been a subject of intensive research. The abundant to-date's evidence relates mostly to the inhibitory action of melatonin on the thyroid growth and function and - to a lesser extent - to the stimulatory effects of thyroid hormones on the pineal gland. It is highly probable that under physiological conditions melatonin and, possibly, other antioxidants regulate ROS generation for thyroid hormone synthesis. We believe that melatonin may protect against extensive oxidative damage in the course of certain thyroid disorders or in case of a harmful action of some external factors on the thyroid. Thus, oxidative damage and the protective action of antioxidants, melatonin included, may occur during both physiological and pathological processes in the thyroid, however, this assumption, requires further studies.     

Systemic regulation of adipose metabolism

White adipose tissue serves as a critical energy storage depot and endocrine organ. Adipocytes are subject to numerous levels of regulation, including neuronal, endocrine and metabolic. While insulin is the classical endocrine regulator of lipid metabolism in adipose tissue, other important endocrine hormones also control adipose tissue physiology. In this review, we will focus on the contribution of the pituitary in the modulation of adipocyte function, through the direct release of growth hormone as well as via the regulation of the thyroid gland and release of thyroid hormone. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.     

Type-II thyroxine 5'-deiodinase is present in the rat pineal gland

Thyroxine-5'-deiodinase has been identified in the rat pineal gland. The characteristics of the enzyme are compatible with a Type-II deiodinase which is tissue-specific and presumably related to generating a local action of thyroid hormone. Our data suggest there may be a previously unrecognized role of thyroid hormone in the regulation of pineal activity.     

A photosensitive circadian oscillator in an insect endocrine gland: photic induction of rhythmic steroidogenesis in vitro

The paired prothoracic glands of the insect Rhodnius prolixus each comprise a group of about 200 structurally identical cells. The synthesis (and release) of steroid moulting hormones (ecdysteroids) by these glands is under circadian control in vivo. We monitored ecdysteroid synthesis by single glands during long-term incubations in vitro. Synthesis is rhythmic in vitro and persists in continuous darkness. Glands which are arrhythmic (from prolonged continuous light) respond to transfer to darkness in vitro with the initiation of a free-running circadian rhythm of ecdysteroid synthesis. Therefore, the glands possess a light-sensitive circadian oscillator. These properties are conventionally associated with nervous tissue of animals. It is suggested that rhythmicity is synchronized within the gland by the known structural and electrical coupling between its component cells. The glands share properties with known pacemakers such as the avian pineal. However, the glands in vivo receive input from both light cues and the cerebral neuropeptide, prothoracicotropic hormone. Rhythmic release of this neuropeptide is controlled by a second oscillator located in the brain. We conclude that the pacemaker in the endocrine system of R. prolixus comprises at least three oscillators, one in each prothoracic gland and one in the brain, which are coupled hormonally. We conclude that the prothoracic gland is an important component of the circadian system controlling development in R. prolixus and that peripheral endocrine glands may play a more active role in the generation of animal circadian organization than has been thought. Accepted: 30 August 1997     

Human pineal luteinizing hormone receptors

The presence of luteinizing hormone receptors in human pineal glands from five females and three males, ranging in age from 61-89 yr, was examined by in situ hybridization and immunocytochemistry. The results demonstrated the presence of these receptors at the mRNA and protein levels in all the pineal glands examined. Pineal gland luteinizing hormone receptors could potentially be involved in the regulation of melatonin synthesis.     

Human pineal luteinizing hormone receptors

The presence of luteinizing hormone receptors in human pineal glands from five females and three males, ranging in age from 61-89 yr, was examined by in situ hybridization and immunocytochemistry. The results demonstrated the presence of these receptors at the mRNA and protein levels in all the pineal glands examined. Pineal gland luteinizing hormone receptors could potentially be involved in the regulation of melatonin synthesis.     

Circadian rhythms of indoleamines and serotonin N-acetyltransferase activity in the pineal gland

Conclusion The circadian rhythm of melatonin synthesis in the pineal glands of various species has been summarized. The night-time elevation of melatonin content is in most if not all cases regulated by the change of N-acetyltransferase activity. In mammals, the N-acetyltransferase rhythm is controlled by the central nervous system, presumably by suprachiasmatic nuclei in hypothalamus through the superior cervical ganglion. In birds, the circadian oscillator that regulates the N-acetyltransferase rhythm is located in the pineal glands. The avian pineal gland may play a biological clock function to control the circadian rhythms in physiological, endocrinological and biochemical processes via pineal hormone melatonin.     

The effect of triiodothyronine on oocyte maturation in the starred sturgeon following exposure to low temperatures and female reservation

A sharp cooling of the sevryuga females as well as their reservation at the spawning temperatures suppress the ability of oocytes coated by follicle membranes to mature under the effect of hypophyseal gonadotrophic hormones in vitro and in vivo. At the same time the oocytes from these females in both the types of experiments are able to mature in vitro in the Ringer solution with progesterone. The injection of triiodthyronine to cooled or reserved females restores the ability of their oocytes to mature under the effect of hypophyseal gonadotrophic hormones both in vivo and in vitro. Such oocytes in our experiments undergo normal development upon fertilization. The thyroid gland hormone (triiodthyronine) influences thus, the ability of follicle epithelium to respond to the effect of hypophyseal gonadotrophic hormones by stimulation of oocyte maturation; this influence of triiodthyronine appears to be indirect. Some practical aspects of this problem are discussed.     

The sympathetic superior cervical ganglia as "little neuroendocrine brains"

The superior cervical ganglia (SCG) provide sympathetic innervation to the pineal gland, cephalic blood vessels, the choroid plexus, the eye, carotid body and the salivary and thyroid glands. Removal of the ganglia brings about several neuroendocrine changes in mammals, including the disruption of water balance in pituitary stalk-sectioned rats and the alteration of normal photoperiodic control of reproduction and thyroid function in hamsters, ferrets, voles, rams and goats. These effects are commonly attributed to pineal denervation. However, pinealectomy does not always mimic ganglionectomy in its neuroendocrine sequelae. This paper discusses several examples illustrating the differences in ganglia and pineal removal, including the acute and chronic effects of ganglionectomy on the control of thyroid response to TSH in rats. A functionally relevant link between SCG and the hypothalamus occurs in rats, inasmuch as ganglionectomy depresses norepinephrine uptake and increases the number and responses of alpha-adrenoceptors in medial basal hypothalamus. Lastly the SCG are active points of concurrency for hormone signals, as revealed by the metabolic changes induced by steroid and anterior pituitary hormones in these structures, even in the absence of intact preganglionic connections, as well as by the existence of putative receptors for some of the hormones, namely estradiol, testosterone and corticosteroids. The SCG appear to constitute a peripheral neuroendocrine center.     

Effects of Pinealectomy and Exogenous Melatonin on the Thyroid Gland Activity Varies in Relation to Reproductive Status of Male Spotted Munia (Lonchura punctulata; Aves,Passeriformes)

The purpose of this investigation was to explore whether the pineal organ and its hormone melatonin has any influence on the activity of thyroid glands, if so, how that relates to the reproductive status of a hitherto unstudied seasonally breeding wild bird. Accordingly, an identical experimental regimen was followed with adult male spotted munia (Lonchura punctulata; Passeriformes) during both its gametogenically active (August-September) and inactive (March-April) phases of the annual reproductive cycle. In either case, the levels of circulating thyroid hormones (both T₃ and T₄) and cellular characteristics of thyroid glands in groups of birds were studied following surgical removal of the pineal gland and/or daily afternoon administration of melatonin (10 μg/ 100 g body weight/ day for 30 days). The results of the same experimental schedule were found to be different depending on the sexual status of the concerned birds. During the breeding phase, pinealectomy (Px) induced significantly decreased values of T₃ and increased for T₄ along with hypertrophy of the thyroid follicular cells (TFC). The changes were reversed in melatonin treated Px birds. An increased amount of T₃ and decreased concentration of serum T₄ were also observed in melatonin injected intact birds. Conversely, the responses of TFC and of thyroid hormones in blood to either Px, or Px with melatonin, or to melatonin alone in intact munias during their inactive reproductive phase were just opposite to those noted during the breeding phase. The results of the present study suggest an influence of the pineal upon the thyroid in spotted munia. Moreover, it appears that this influence is carried out by melatonin, the action of which is reversible in relation with the gametogenic status of the concerned avian species.     

Pineal modulation of thymus and immune function in a seasonally breeding tropical rodent, Funambulus pennanti

The immune system driven by cytokines is now known to be influenced by various other endocrine glands and its hormones. Results of the present study indicate a bidirectional relation between the pineal-thymus axis and the immune system status of an Indian tropical rodent, Funambulus pennanti, during winter months (reproductive inactive phase), when it faces maximum challenges from nature. Pinealectomy during the reproductive inactive phase inhibited thymus and spleen functions, which resulted in significant changes in leukocyte and lymphocyte counts and T-cell-mediated immune function (measured in terms of delayed-type hypersensitivity response to oxazolone). Blastogenic responses of lymphoid cells (thymocytes, splenocytes, and lymph node cells) also decreased following ablation of the pineal gland. To check the definite role of the pineal gland we injected melatonin into pinealectomized squirrels, and the suppressed immune function was significantly restored. Neuroendocrine control of the pineal gland on the histocompatible tissues in this seasonal breeder, F. pennanti, suggests an adaptive mechanism of the immune system for survival in the tropical zone. J. Exp. Zool. 289:90-98, 2001.     

Expression of Secretogranin III in Chicken Endocrine Cells: Its Relevance to the Secretory Granule Properties of Peptide Prohormone Processing and Bioactive Amine Content

The expression of secretogranin III (SgIII) in chicken endocrine cells has not been investigated. There is limited data available for the immunohistochemical localization of SgIII in the brain, pituitary, and pancreatic islets of humans and rodents. In the present study, we used immunoblotting to reveal the similarities between the expression patterns of SgIII in the common endocrine glands of chickens and rats. The protein–protein interactions between SgIII and chromogranin A (CgA) mediate the sorting of CgA/prohormone core aggregates to the secretory granule membrane. We examined these interactions using co-immunoprecipitation in chicken endocrine tissues. Using immunohistochemistry, we also examined the expression of SgIII in a wide range of chicken endocrine glands and gastrointestinal endocrine cells (GECs). SgIII was expressed in the pituitary, pineal, adrenal (medullary parts), parathyroid, and ultimobranchial glands, but not in the thyroid gland. It was also expressed in GECs of the stomach (proventriculus and gizzard), small and large intestines, and pancreatic islet cells. These SgIII-expressing cells co-expressed serotonin, somatostatin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, or insulin. These results suggest that SgIII is expressed in the endocrine cells that secrete peptide hormones, which mature via the intragranular enzymatic processing of prohormones and physiologically active amines in chickens.     

Purinergic signalling in endocrine organs

There is widespread involvement of purinergic signalling in endocrine biology. Pituitary cells express P1, P2X and P2Y receptor subtypes to mediate hormone release. Adenosine 5′-triphosphate (ATP) regulates insulin release in the pancreas and is involved in the secretion of thyroid hormones. ATP plays a major role in the synthesis, storage and release of catecholamines from the adrenal gland. In the ovary purinoceptors mediate gonadotrophin-induced progesterone secretion, while in the testes, both Sertoli and Leydig cells express purinoceptors that mediate secretion of oestradiol and testosterone, respectively. ATP released as a cotransmitter with noradrenaline is involved in activities of the pineal gland and in the neuroendocrine control of the thymus. In the hypothalamus, ATP and adenosine stimulate or modulate the release of luteinising hormone-releasing hormone, as well as arginine-vasopressin and oxytocin. Functionally active P2X and P2Y receptors have been identified on human placental syncytiotrophoblast cells and on neuroendocrine cells in the lung, skin, prostate and intestine. Adipocytes have been recognised recently to have endocrine function involving purinoceptors.     

Metabolic regulation by alpha 1- and alpha 2-adrenoceptors.

The role of alpha-adrenoceptors in the mediation of autonomic function, particularly in the control of the cardiovascular system, is widely known. However, alpha-adrenoceptors are also important in the regulation of a variety of metabolic processes that occur in the body either through direct action or by stimulation of the release of other mediators that control metabolic function. Thus, alpha 2-adrenoceptor activation by circulating or neuronally released catecholamines inhibits the release of insulin from pancreatic islet beta-cells and, by inhibiting this response, alpha 2-adrenoceptor antagonists have been shown to have an antihyperglycemic effect. The alpha-adrenoceptor-mediated regulation of the release of pituitary hormones is indirect, with alpha-adrenoceptors being located on peptidergic neurons in the hypothalamus that secrete releasing hormones into the hypophysial portal system to regulate the secretion of hormones from the anterior pituitary gland. Thus, the increase in cortisol secretion from the adrenal glands following a meal is produced, at least in part, by an alpha 1-adrenoceptor-mediated increase in vasopressin and CRF-41 secretion from neurons on the hypothalamus that stimulate the release of adrenocorticotrophic hormone secretion from the pituitary gland, which subsequently stimulates the synthesis and release of cortisol from the adrenal medulla. In addition to metabolic regulation by alpha 1- and alpha 2-adrenoceptors within the endocrine system, alpha-adrenoceptors are also a component of the system that regulates certain aspects of metabolism within autonomic effector cells, such as the control of smooth muscle cell division and growth during periods of continued alpha-adrenoceptor activation as a result of activation of second messenger systems.     

Effects of high-altitude hypoxia on the hormonal response to hypothalamic factors

Acute and chronic exposure to high altitude induces various physiological changes, including activation or inhibition of various hormonal systems. In response to activation processes, a desensitization of several pathways has been described, especially in the adrenergic system. In the present study, we aimed to assess whether the hypophyseal hormones are also subjected to a hypoxia-induced decrease in their response to hypothalamic factors. Basal levels of hormones and the responses of TSH, thyroid hormones, prolactin, sex hormones, and growth hormone to the injection of TRH, gonadotropin-releasing hormone, and growth hormone-releasing hormone (GHRH) were studied in eight men in normoxia and on prolonged exposure (3-4 days) to an altitude of 4,350 m. Thyroid hormones were elevated at altitude (+16 to +21%), while TSH levels were unchanged, and follicle-stimulating hormone and prolactin decreased, while leutinizing hormone was unchanged. Norepinephrine and cortisol levels were elevated, while no change was observed in levels of epinephrine, dopamine, growth hormone (GH), IGF-1, and IGFBP-3. The mean response to hypothalamic factors was similar in both altitudes for all studied hormones, although total T4 was lower in hypoxia during 45 to 60 min after injection. The effect of hypoxia on the hypophyseal response to hypothalamic factors was similar among subjects, except for the GH response to GHRH administration. We conclude that prolonged exposure to high-altitude hypoxia induces contrasted changes in hormonal levels, but the hypophyseal response to hypothalamic factors does not appear to be blunted.     

A computational model of the human thyroid

The thyroid, the largest gland in the endocrine system, secretes hormones that help promote bodily growth and development. This gland regulates hormonal secretion rate in spite of changes in dietary iodine which is a key ingredient in the hormone's biosynthesis. The thyroid relies on several feedback mechanisms for this regulation, and in this paper we use recent molecular-level and clinical observations to engineer a computational thyroid model. We use simulation and analysis to show that this models captures known aspects of thyroid physiology. We identify features in the model that are responsible for hormonal regulation, and use the model to identify and evaluate competing hypotheses associated with Wolff-Chaikoff escape.     

Excretion, Metabolism and Enterohepatic Circulation Pathways and Their Role in Overall Thyroid Hormone Regulation in the Rat

Regulation of thyroid, adrenocortical and other hormones secretedby the major endocrine glands in mammals is widely attributedprimarily to feedback control relationships with the pituitary,hypothalamus or both, with hepatobiliary and intestinal mechanismshaving no more than a passive or excretory role. I present anotherview of enterohepatic components in thyroid endocrine function,suggesting a functional and more pervasive role for the intestine,in a more complex hierarchical system controlling thyroid hormonelevels, effects and economy in the rat, and possibly in othermammals. A central factor is the existence of enterohepaticcycling of these hormones, or their reabsorption from intestnalpools to portal and then systemic blood. This process affectstheir dynamic behavior throughout the organism, not only hormoneeconomy, because bidirectional transport of hormone betweenblood and intestine (including large pools in luminal contents)renders all or part of the gut internal to the system regulatingthyroid hormones. We review the evidence for and possible significanceof this hypothesis, covering specific aspects of hormone levelcontrol in the rat, including the deiodination, conjugationand other metabolic pathways, particularly in liver and intestine,and the fecal and urinary excretory (sink) and hormone production(source) pathways. The modulators of enterohepatic subsystemregulation of thyroid hormones are postulated to involve thecombined effects of hormone conjugation and degradation processesin liver and their subsequent secretion in bile, coupled withthe bacterial deconjugation, the reabsorption and certain hormonestorage mechanisms of the intestine.     

Activity and expression of ecto-5′-nucleotidase/CD73 are increased by thyroid hormones in vascular smooth muscle cells

Extracellular nucleotides ATP, ADP, AMP and adenosine are well known signaling molecules of the cardiovascular system that are involved in several physiological processes: cell proliferation, platelet aggregation, inflammatory processes and vascular tonus. The levels of these molecules are controlled by ecto-NTPDases and ecto-5′-nucleotidase/CD73 (ecto-5′-NT/CD73) actions, which are responsible for the complete ATP degradation to adenosine. The thyroid hormones, thyroxine (T₄) and triiodothyronine (T₃), play important roles in the vascular system promoting vasodilatation. Here we investigated the influence of thyroid hormones on the enzyme cascade that catalyzes the interconversion of purine nucleotides in vascular smooth muscle cells (VSMC). Exposure of VSMCs to 50nM T₃ or T₄ did not change ATP and ADP hydrolysis significantly. However, the same treatment caused an increase of 75% in AMP hydrolysis, which was time-dependent but dose-independent. Moreover, T₃ treatment significantly increased ecto-5′-NT/CD73 mRNA expression, which suggests a genomic effect of this hormone upon ecto-5′-NT/CD73. In addition to the importance of the ecto-5′-NT in cell proliferation and differentiation, its overexpression could result in higher extracellular levels of adenosine, an important local vasodilatator molecule.