Distribution of calcitonin cells in the thyroid glands of normal adult rhesus monkeyMacaca mulatta

Summary The calcitonin cells of adult rhesus monkeyMacaca mulatta are located in the central region of thyroid along the median axis. The anterior and posterior poles, the isthmus and peripheral regions of thyroid are completely devoid of C cells. The parathyroid also lacks C cells.     

Aldolase C is localized in neuroendocrine cells

To elucidate the localization of the subunit C of aldolase (aldolase C) in peripheral neuroendocrine cells, we made an immunohistochemical study with monospecific antibodies against human aldolase C. Aldolase C was found to be localized in various types of neuroendocrine cells; in the pituitary gland, thyroid, pancreas, adrenal gland, bronchus, and gastrointestinal tract.     

Aldolase C is localized in neuroendocrine cells

Summary To elucidate the localization of the subunit C of aldolase (aldolase C) in peripheral neuroendocrine cells, we made an immunohistochemical study with monospecific antibodies against human aldolase C. Aldolase C was found to be localized in various types of neuroendocrine cells; in the pituitary gland, thyroid, pancreas, adrenal gland, bronchus, and gastrointestinal tract.     

Endocrine cells producing regulatory peptides

Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.     

Thyroid hormone receptor-mediated regulation of the methionine adenosyltransferase 1 gene is associated with cell invasion in hepatoma cell lines

The thyroid hormone T₃ regulates differentiation, growth, and development. We demonstrated that methionine adenosyltransferase 1A (MAT1A) was positively regulated by T₃ identified by cDNA microarray previously. The expression of the MAT1A was upregulated by T₃ in hepatoma cell lines overexpressing thyroid hormone receptors (TRs). Additionally, these findings indicate that MAT1A may be regulated by CCAAT/enhancer binding protein (C/EBP). The critical role of the C/EBP binding sites was confirmed by the reporter or chromatin immuno-precipitation (ChIP) assay. In addition, C/EBP was upregulated in hepatoma cells after T₃ treatment and ectopic expression of MAT1A inhibited cell migration and invasion in J7 hepatoma cells. Conversely, knockdown of MAT1A expression increased cell migration. Together, these findings suggest that the expression of the MAT1A gene is mediated by C/EBP and is indirectly upregulated by T₃. Finally, TR was downregulated in a small subset of hepatocellular carcinoma cells concomitantly reduced the expression of C/EBPα and MAT1A.     

Endorcine cells producing regulatory peptides

Summary Recent data on the immunologication of regulatory peptides and related propeptide sequences in endocrine cells and tumours of the gastrointestinal tract pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory beenrevised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptidesare the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, -MSH and CLIP (corticotropoin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenalin-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.     

Effect of cold exposure on electrophysiological properties of rat heart

Male rats exposed to the cold (4°C) for five or ten days exhibited modifications in their thyroid state, as documented by increases in serum thyroid hormone levels, to which differently graded modifications of heart weight/body weight ratio, heart rate, and resting metabolic rate were associated. The values of the above mentioned thyroid state indicators returned to those of the control when the animals, kept at cold for ten days, were re-exposed to room temperature (24°C) for an additional 10 days. The configuration of action potentials, recorded in vitro at 26°C from fibres of anterior papillary muscles, was different in control rats of different age and was affected by prolonged cold exposure. In fact, the action potential duration (APD) increased after ten days of cold exposure. In the re-exposed group the APD was not different from that of the controls. Such a pattern was not significantly modified when the stimulation frequency increased from 1 Hz to 5 Hz. The above results suggest that in cold exposure, as in experimental hyperthyroidism, thyroid hormone might exert a cardiac chronotropic effect by modifying heart electrophysiological properties. Thus thyroid hormone should play a basic role during the exposure to cold environment, stimulating the body metabolism and increasing heart rate as a response to the requirement for greater tissue perfusion.     

Activation and inactivation of thyroid hormone by deiodinases: Local action with general consequences

The thyroid hormone plays a fundamental role in the development, growth, and metabolic homeostasis in all vertebrates by affecting the expression of different sets of genes. A group of thioredoxin fold-containing selenoproteins known as deiodinases control thyroid hormone action by activating or inactivating the precursor molecule thyroxine that is secreted by the thyroid gland. These pathways ensure regulation of the availability of the biologically active molecule T3, which occurs in a time-and tissue-specific fashion. In addition, because cells and plasma are in equilibrium and deiodination affects central thyroid hormone regulation, these local deiodinase-mediated events can also affect systemic thyroid hormone economy, such as in the case of non-thyroidal illness. Heightened interest in the field has been generated following the discovery that the deiodinases can be a component in both the Sonic hedgehog signaling pathway and the TGR-5 signaling cascade, a G-protein-coupled receptor for bile acids. These new mechanisms involved in deiodinase regulation indicate that local thyroid hormone activation and inactivation play a much broader role than previously thought. Received 29 August 2007; received after revision 11 October 2007; accepted 16 October 2007     

Demonstration of a basal lamina in cocultures of thyroid cells and embryonal swine skin cells]

Porcine thyroid and embryo skin cells were isolated and cultured. Cultures from each kind of cells, as well as cocultures were fixed twice a week for electron microscopy. On day 8th a basal lamina like material appears only in the cocultures, along the basal plasmalemma of the reassociated thyroid cells. This amorphous material increases up to day 17th.     

Detection of the H-RAS oncogene in human thyroid anaplastic carcinomas

We have transfected high-molecular-weight DNA from human thyroid carcinomas into murine 3T3 cells. As a result we identified several foci of morphologically distinct transformed cells in each of the tumour DNA transfected cultures. After a total of three rounds of transfection, the transformed cells were shown to form tumours in nude mice. Southern blot analysis of DNA prepared from third-round transfectants demonstrated the presence of human Alu repetitive sequences and, after hybridization with probes for known oncogenes, indicated the presence of the human H-RAS oncogene in 3T3 cells transfected with three out of four anaplastic carcinoma DNA samples. It appears therefore that activation of RAS genes may be an important event in the development of the anaplastic thyroid tumours.     

Allogeneic effect on induction of thyroglobulin antibodies and thyroid lesions in mice

Summary All previous attempts failed to induce thyroglobulin antibodies or thyroid infiltrates in mice immunized with homologous thyroglobulin without adjuvants. However, an allogeneic effect obviated the need of adjuvants for triggering thyroglobulin-reactive lymphocytes to produce thyroglobulin antibodies or thyroid lesions.This work was supported by a grant from the Margaret Duffy and Robert Cameron C. Troup Fund. I thank Ellen Kenney for technical assistance and Dr Pei-nan Tsung for the X-ray irradiation.     

Detection of theH-RAS oncogene in human thyroid anaplastic carcinomas

Summary We have transfected high-molecular-weight DNA from human thyroid carcinomas into murine 3T3 cells. As a result we identified several foci of morphologically distinct transformed cells in each of the tumour DNA transfected cultures. After a total of three rounds of transfection, the transformed cells were shown to form tumours in nude mice. Southern blot analysis of DNA prepared from third-round transfectants demonstrated the presence of human Alu repetitive sequences and, after hybridization with probes for known oncogenes, indicated the presence of the humanH-RAS oncogene in 3T3 cells transfected with three out of four anaplastic carcinoma DNA samples. It appears therefore that activation ofRAS genes may be an important event in the development of the anaplastic thyroid tumours.     

Effects of thyroxine and exercise on the glandular and plasma levels of corticosterone in the male rat

Summary The results presented here demonstrates that the thyroid gland is essential for normal corticosterone production. They further show that exercise stimulates this production whether the thyroid gland is present or not. The release or metabolism of corticosterone seems dependent upon an intact thyroid gland since plasma levels of corticosterone are decreased during exercise if the thyroid is absent. The administration of thyroxine is not sufficient to renew these levels.     

Inactivation of Ret/Ptc1 oncoprotein and inhibition of papillary thyroid carcinoma cell proliferation by indolinone RPI-1

Genetic alterations causing oncogenic activation of the RET gene are recognized as pathogenic events in papillary and medullary thyroid carcinomas. Inhibition of Ret oncoprotein functions could thereby represent a specific therapeutic approach. We previously described the inhibitory activity of the 2-indolinone derivative RPI-1 (formerly Cpd1) on the tyrosine kinase activity and transforming ability of the products of the RET/PTC1 oncogene exogenously expressed in murine cells. In the present study, we investigated the effects of RPI-1 in the human papillary thyroid carcinoma cell line TPC-1 spontaneously harboring the RET/PTC1 rearrangement. Treatment with RPI-1 inhibited cell proliferation and induced accumulation of cells at the G2 cell cycle phase. In treated cells, Ret/Ptc1 tyrosine phosphorylation was abolished along with its binding to Shc and phospholipase C, thereby indicating abrogation of constitutive signaling mediated by the oncoprotein. Activation of JNK2 and AKT was abolished, thus supporting the drug inhibitory efficacy on downstream pathways. In addition, cell growth inhibition was associated with a reduction in telomerase activity by nearly 85%. These findings in a cellular context relevant to the pathological function of RET oncogenes support the role of Ret oncoproteins as useful targets for therapeutic intervention, and suggest RPI-1 as a promising candidate for preclinical development in the treatment of thyroid tumors expressing RET oncogenes.Received 31 December 2002; received after revision 21 February 2003; accepted 10 April 2003     

Effects of TSH and cyclic AMP on the human thyroid cells cultured in a chemically defined medium.

In a serum-free, chemically defined medium human thyroid cells elongated remarkably and resembled fibroblastic cells. They retained the cyclic AMP response to TSH and the supplement of medium with TSH or dibutyryl cyclic AMP permitted the preservation of epithelial nature by the cells. Cyclic AMP of the cells of epithelial nature was higher than those of fibroblastic appearance.     

Effects of altered thyroid state on the inhibition produced by locus coeruleus in purkinje cells in the rat

Summary The number of cerebellar Purkinje cells inhibited after locus coeruleus stimulation was found to be greater in hyperthyroid rats than in control healthy animals; these in turn showed a higher percentage of inhibited cells than hypothyroid rats. It is concluded that thyroid hormone is capable of modulating synaptic activity in the LC-PC pathway.     

Effects of TSH and cyclic AMP on the human thyroid cells cultured in a chemically defined medium

Summary In a serum-free, chemically defined medium human thyroid cells elongated remarkably and resembled fibroblastic cells. They retained the cyclic AMP response to TSH and the supplement of medium with TSH or dibutyryl cyclic AMP permitted the preservation of epithelial nature by the cells. Cyclic AMP of the cells of epithelial nature was higher than those of fibroblastic appearance.     

Serotonin-containing cells in the ascidian endostyle

Summary In the ascidian endostyle, all fluorescence due to serotonin is localized in the peripheral, iodine-binding area of the endostylar epithelium, which is homologous to the vertebrate thyroid. The amine appears to be stored in granule-containing cells which may correspond to the vertebrate calcitocytes.We are grateful to Dr M.P. Gorbunova for helpful advise and diseussion.     

Zur Frage des Angriffspunktes des Thiouracil

Summary The mechanism of action of thiouracil and thiourea was investigated on Xenopus tadpoles. Both substances are able to stop metamorphotic changes if administered early enough. Characteristic disturbances occur in the epithelium of the thyroid follicles after only 24 hours. The action of these substances over a period of several weeks may lead to goitre. In the pituitary anterior lobe, on the other hand, the same characteristic changes take place in the basophilic cells as after thyroidectomy. The thyroid structure of hypophysectomised tadpoles corresponds to that of untreated hypophysectomised animals. Thiourea and thiouracil do not inhibit the thyroxine effect on thyroidectomised and hypophysectomised tadpoles. These findings indicate that the point of attack of thiouracil and thiourea lies in the follicular epithelium of the thyroid, and thus supportAstwood's hypothesis.     

Immunocytochemical demonstration of calmodulin in cells secreting by exocytosis

Calmodulin is a regulator of several calcium-dependent cellular processes. It has been suggested that it plays a role in the mechanism of secretion. Employing an indirect immunoperoxidase technique at the light microscope level, this study demonstrates the presence of calmodulin in several exocytotic cells (mast cells, thyroid follicular cells, neurohypophyseal neurosecretory terminals, pancreatic beta-cells and pancreatic acinus cells) in rat and man. The positive staining reaction for calmodulin was granular and at least in the case of rat mast cells it appeared to be associated with the granule membrane.