Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid C cells, or parafollicular cells, are mainly known for producing calcitonin, a hormone involved in calcium homeostasis with hypocalcemic and hypophosphatemic effects. Classically, the main endocrine activity of this cell population has been believed to be restricted to its roles in serum calcium and bone metabolism. Nonetheless, in the last few years evidence has been accumulating in the literature with regard to local regulatory peptides secreted by C cells, such as somatostatin, ghrelin, thyrotropin releasing hormone or the recently described cocaine- and amphetamine-related transcript, which could modify thyroid function. As thyrotropin is the main hormone controlling the hypothalamic-pituitary-thyroid axis and, accordingly, thyroid function, we have examined the functional expression of the thyrotropin receptor in C-cell lines and in thyroid tissues. We have found that rat and human C-cell lines express the thyrotropin receptor at both mRNA and protein levels. Furthermore, incubation of C cells with thyrotropin resulted in a 10-fold inhibition of thyrotropin-receptor expression, and a concomitant decrease of the steady-state mRNA levels for calcitonin and calcitonin gene-related peptide determined by quantitative real-time PCR was found. Finally, thyrotropin receptor expression by C cells was confirmed at protein level in both normal and pathological thyroid tissues by immunohistochemistry and immunofluorescence. These results confirm that C cells, under regulation by thyrotropin, are involved in the hypothalamic-pituitary-thyroid axis and suggest a putative role in local fine-tuning of follicular cell activity.
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PMID:Functional expression of the thyrotropin receptor in C cells: new insights into their involvement in the hypothalamic-pituitary-thyroid axis. 1949 88

While TSH-producing adenoma (TSHoma) is rare, the diagnosis is often delayed because the clinical features are heterogeneous. The patient was a 69-year-old woman who had been referred to the Yachiyo Medical Center in August 2008, because of dyspnea, loss of appetite, weight loss of 10 kg, and diarrhea that lasted 4 years. We diagnosed this patient with pituitary TSH-producing macroadenoma. Thyroid hormone concentration was increasing although the serum TSH level was within a normal range after trans-sphenoidal surgery. We considered that because of enlargement of the thyroid gland due to long-term stimulation by TSH, a low concentration of TSH could stimulate the thyroid gland to produce excess T3 or T4. The somatostatin analogue, octreotide was used to control the TSHoma and serum TSH concentration but not thyroid hormone. The octreotide in combination with thiamazole treatment for 14 months controlled thyroid hormone concentration and decreased the thyroid mass, and ultimately, the thiamazole could be stopped. To date, the use of combination therapy of octreotide with thiamazole in patients with remaining TSH-producing adenoma without Basedow's disease is rare, and we suggest that this treatment is one of the therapeutic means to treat recurrence of TSH-producing adenoma after surgery with progressive complications or large thyroid gland.
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PMID:A case of TSH-producing adenoma treated with octreotide in combination with thiamazole for the control of TSH and thyroid hormones after trans-sphenoidal neurosurgery. 2151 53

Thyroid hormones are essential regulators of growth, development and normal bodily function and their release is coordinated by the hypothalamic-pituitary-thyroid (HPT) axis. While the HPT axis has been established as an acutely stress-responsive neuroendocrine system, relatively little is known about the mechanisms of its stress regulation. The present study examined acute stress-induced changes in peripheral hormone levels [triiodothyronine (T3); thyroxine (T4), thyroid-stimulating hormone (TSH), reverse triiodothyronine (rT3)] and central mRNA levels of regulators of the HPT axis [thyrotropin-releasing hormone (TRH), somatostatin (SST), type II deiodinase (D2)] in response to an inescapable tail-shock, a rodent model of stress. Additionally, we examined whether individual differences in spontaneous exploratory behavior in an open field test predicted basal levels of TH or differential susceptibility to the effects of stress. The stress condition was associated with decreases in peripheral T3, T4 and TSH, but not rT3, when compared with controls. No changes were observed in TRH or SST mRNA levels, but there was a trend suggesting stress-related increases in D2 mRNA. We also found that an animal's exploratory behavior in an unfamiliar open field arena was positively related to peripheral thyroid hormone levels and predicted the magnitude of stress-induced changes. In conclusion, we found suggestive evidence for stress-induced decrease in central drive HPT axis, but the central mechanisms of its stress regulation remain to be elucidated. Additionally, we found that individual differences in animals' exploratory behavior were correlated with peripheral TH levels.
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PMID:Thyroid hormone regulation by stress and behavioral differences in adult male rats. 2168 56

Thyroid diseases are the commonest endocrine disorders in the general population. In most of the cases, they are consistent with benign conditions which may be asymptomatic or affect people at a variable extent. Since they often represent chronic conditions their prevalence increases by age and reaches in elderly the highest rates. Thyroid nodules are a common clinical finding. Most subjects with thyroid nodules have few or no symptoms. Thyroid nodules are more commonly non-functioning. However, in elderly, toxic multinodular goiter is the most frequent cause of spontaneous hyperthyroidism and often, it emerges insidiously from nontoxic multinodular goiter. Although autoimmune thyroiditis is the most common cause of hypothyroidism in elderly subjects, other causes, such as drugs, neck radiotherapy, thyroidectomy or radioiodine therapy, are frequently observed among these subjects. A small subset of medications including dopamine agonists, glucocorticoids and somatostatin analogs affect thyroid function through suppression of TSH. Other medications that may affect TSH levels are metformin, antiepileptic medications, lithium carbonate and iodine-containing medications. Other drugs can alter T4 absorption, T4 and T3 transport in serum and metabolism of T4 and T3, such as proton-pump inhibitors and antacids, estrogens, mitotane and fluorouracil, phenobarbital and rifampin. Amiodarone administration is associated with thyrotoxicosis or hypothyroidism. Thyroid cancer has similar characteristics in elderly as in general population, however the rate of aggressive forms such as the anaplastic histotype, is higher in older than younger subjects. Diagnosis of thyroid diseases includes a comprehensive medical history and physical examination and appropriate laboratory tests. A correct diagnosis of thyroid diseases in the elderly is crucial for proper treatment, which consists in the removal of medications that may alter thyroid function, in the use of levo-thyroxine in case of hypothyroidism, anti-thyroid drugs in case of hyperthyroidism and use of surgery, radioiodine therapy and percutaneous ablative procedures in selected cases. In conclusion, thyroid diseases in patients older than 60 years deserve attention from different points of view: the prevalence is different from the young adult; symptoms are more nuanced and makes difficult the diagnosis; age and comorbidity often force therapeutic choices and may limit safety and efficacy of therapy. Finally, in elderly patients for whom specific therapy is necessary, more gradual and careful therapeutic approach and close follow-up are recommended in order to minimize the alterations of thyroid function which are induced by many drugs commonly used in clinical practice.
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PMID:Thyroid diseases in elderly. 2201 51

The classical attitude of Nuclear Medicine practitioners on matters of peptide-receptor interactions has maintained an intrinsic monogamic character since many years. New advances in the field of biochemistry and even in clinical Nuclear Medicine have challenged this type of thinking, which prompted me to work on this review. The central issue of this paper will be the use of somatostatin analogs, i.e., octreotide, in clinical imaging procedures as well as in relation to neuroendocirne tumors. Newly described characteristics of G-protein coupled receptors such as the formation of receptor mosaics will be discussed. A small section will enumerate the regulatory processes found in the cell membrane. Possible new interpretations, other than tumor detection, based on imaging procedures with somatostatin analogs will be presented. The readers will be taken to situations such as inflammation, nociception, mechanosensing, chemosensing, fibrosis, taste, and vascularity where somatostatin is involved. Thyroid-associated orbitopathy will be used as a model for the development of multi-agent therapeutics. The final graphical summary depicts the multifactorial properties of ligand binding.
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PMID:Reflections on the theory of "silver bullet" octreotide tracers: implications for ligand-receptor interactions in the age of peptides, heterodimers, receptor mosaics, truncated receptors, and multifractal analysis. 2221 90

Recent discoveries in molecular biology offer new perspectives in the treatment of endocrine tumors. There is currently no medical therapy for Cushing's disease that targets the pituitary adenoma. Pasireotide, a new somatostatin analog, demonstrates a strong affinity for somatostatin receptors expressed by corticotroph adenomas. Some recent clinical trials showed a decrease of urinary free cortisol with pasireotide. This new treatment could be useful in case of pituitary surgery failure. Thyroid tumorigenesis involves kinase signaling cascade. Tyrosine-kinase inhibitors have now been tested in the treatment of progressive differentiated iodine refractory thyroid carcinomas or medullary carcinomas and showed modestly encouraging results.
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PMID:[Endocrinology]. 2230 34

Thyroid hormone (TH) plays an important role in brain development, and TH deficiency during pregnancy or early postnatal periods leads to neurological disorders such as cretinism. Hypothyroidism reduces the number of parvalbumin (PV)-positive interneurons in the neocortex and hippocampus. Here we used a mouse strain (growth-retarded; grt) that shows growth retardation and hypothyroidism to examine whether somatostatin (Sst)-positive interneurons that are generated from the same pool of neural progenitor cells as PV-positive cells are also altered by TH deficiency. The number of PV-positive interneurons was significantly decreased in the neocortex and hippocampus of grt mice as compared with normal control mice. In contrast to the decrease in the number of PV neurons, the number of Sst-positive interneurons in grt mice was increased in the stratum oriens of the hippocampus and the hilus of the dentate gyrus, although their number was unchanged in the neocortex. These changes were reversed by triiodothyronine administration from postnatal day (PD) 0 to 20. TH supplementation that was initiated after PD21 did not, however, affect the number of PV- or Sst-positive cells. These results suggest that during the first three postnatal weeks, TH may be critical for the generation of subpopulations of interneurons.
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PMID:Amelioration of improper differentiation of somatostatin-positive interneurons by triiodothyronine in a growth-retarded hypothyroid mouse strain. 2433 74

Hyperthyroidism is mainly due to autoimmune thyroid disorders or toxic goiter, and very rarely to the presence of thyrotropin (TSH)-secreting pituitary adenomas (TSHomas). These tumors are characterized by high levels of circulating free thyroid hormones (FT4 and FT3) in the presence of nonsuppressed serum TSH concentrations. Failure to correctly diagnose TSHomas may result in inappropriate thyroid ablation, which results in a significant increase of pituitary tumor mass. The diagnosis is mainly achieved by measuring TSH after T3 suppression and TRH stimulation tests. These dynamic tests, together with pituitary imaging and genetic testing are useful in distinguishing TSHomas from the syndromes of resistance to thyroid hormone action. The treatment of choice is surgery. In cases of surgical failure, somatostatin analogs have been found to be effective in normalizing TSH secretion in more than 90% of patients.
Eur Thyroid J 2013 Jun
PMID:2013 European thyroid association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors. 2478 44

Thyroid hormones (TH) play a key role in regulation of seasonal as well as acute changes in metabolism. Djungarian hamsters (Phodopus sungorus) adapt to winter by multiple changes in behaviour and physiology including spontaneous daily torpor, a state of hypometabolism and hypothermia. We investigated effects of systemic TH administration and ablation on the torpor behaviour in Djungarian hamsters adapted to short photoperiod. Hyperthyroidism was induced by giving T4 or T3 and hypothyroidism by giving methimazole (MMI) and sodium perchlorate via drinking water. T3 treatment increased water, food intake and body mass, whereas MMI had the opposite effect. Continuous recording of body temperature revealed that low T3 serum concentrations increased torpor incidence, lowered Tb and duration, whereas high T3 serum concentrations inhibited torpor expression. Gene expression of deiodinases (dio) and uncoupling proteins (ucp) were analysed by qPCR in hypothalamus, brown adipose tissue (BAT) and skeletal muscle. Expression of dio2, the enzyme generating T3 by deiodination of T4, and ucps, involved in thermoregulation, indicated a tissue specific response to treatment. Torpor per se decreased dio2 expression irrespective of treatment or tissue, suggesting low intracellular T3 concentrations during torpor. Down regulation of ucp1 and ucp3 during torpor might be a factor for the inhibition of BAT thermogenesis. Hypothalamic gene expression of neuropeptide Y, propopiomelanocortin and somatostatin, involved in feeding behaviour and energy balance, were not affected by treatment. Taken together our data indicate a strong effect of thyroid hormones on torpor, suggesting that lowered intracellular T3 concentrations in peripheral tissues promote torpor.
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PMID:Thyroid hormone status affects expression of daily torpor and gene transcription in Djungarian hamsters (Phodopus sungorus). 2643 75

Metastases of differentiated thyroid cancer (DTC) can lose affinity to radioiodine with the passage of time, with resultant difficulty in management. Thyroid tumors are known to express somatostatin receptors and therefore 111In-pentetreotide, somatostatin analogue, can visualize tumors with high concentration of somatostatin receptors. We report a case of I-131 whole body scan (WBS) negative recurrent metastatic papillary thyroid carcinoma with positive 18F FDG PET-CT and 111In-pentetreotide scan. Somatostatin receptor scintigraphy (SRS) with 111In-pentetreotide may be useful both in the staging and monitoring of patients with non-iodine avid carcinoma of the thyroid. 111In-pentetreotide scan positive patients are potential candidates for somatostatin receptor-targeted therapy.
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PMID:111In-pentetreotide scintigraphy and 18F FDG PET-CT in differentiated thyroid carcinoma metastases with negative whole body radioiodine scan. 2649 23


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