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)

The insulin-like growth factors (IGFs) exist primarily bound to cell surface receptors or complexed to specific binding proteins (IGFBPs). The IGFBPs modulate the bioavailability of the IGFs and may enhance or inhibit IGF actions. Several distinct forms of IGFBPs have been described on the basis of size, immunological determinants, and distribution in biological fluids; the IGFBPs may differ as well in their biological function. Sheep thyroid cells produce IGFBPs under hormonal regulation. Cells grown in basal medium or with six-hormone (6H) medium supplements (transferrin, glycyl-histidyl-lysine, hydrocortisone, somatostatin, insulin, and TSH) release nonglycosylated BPs that migrate at 24, 27, 29, and 32 kDa on Western ligand blot. Cells cultured with the thyroid mitogens epidermal growth factor and phorbol ester release additional glycosylated IGFBPs of 40-44 kDa. Immunoprecipitation experiments indicate that 29- and 32-kDa IGFBPs are antigenically related to IGFBP-2, and the 40- to 44-kDa proteins are related to IGFBP-3. Using specific cDNA probes IGFBP-1, -2, and -3, we examined the regulation of IGFBP mRNA levels in sheep thyroid cultures. The rat IGFBP-2 cDNA probe hybridized to an approximately 1.6-kilobase mRNA species in cells under all culture conditions. However, IGFBP-3 mRNA was detectable only in epidermal growth factor- or phorbol ester-treated cells and appeared within 4 h, preceding the release of IGFBP-3 protein into the medium. The 6H additives, which stimulate differentiated function in thyroid cells, inhibited the mRNA levels of both IGFBP-2 and IGFBP-3. IGFBP-1 mRNA was not detectable. The distinct regulation of these IGFBPs suggest that they may play different biological roles in modulating thyroid physiology.
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PMID:Regulation of insulin-like growth factor-binding protein messenger ribonucleic acid levels in sheep thyroid cells. 170 62

The action of somatostatin (SRIH) on 3H-thymidine (thy) incorporation and on c-myc and thyroglobulin RNA levels in a suspension of follicles from normal and goitrous human thyroid was examined. SRIH, at 10(-7) M concentration, inhibited basal thy incorporation (maximally by 4 h lasting for up 24 h), which effect was greater in goiter than in normal thyroid and was also detected in growing adherent epithelial cells. Moreover, in a follicle suspension SRIH prevented TSH-stimulated thy incorporation, both in normal and in goitrous thyroid. Basal expression of c-myc RNA was not affected by SRIH in either tissue, whereas the TSH-stimulated c-myc RNA level was significantly reduced in goiter. No effect of SRIH was observed on basal or TSH-stimulated thyroglobulin RNA levels. SRIH did not alter basal cAMP concentrations in normal or goitrous follicles, but it significantly reduced TSH-stimulated cAMP accumulation both in normal thyroid and in goiter. Overall, our data indicate a direct inhibitory action of SRIH on growth, but not on differentiation, of human thyroid, probably by a mechanism not entirely cAMP dependent.
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PMID:Somatostatin reduces 3H-thymidine incorporation and c-myc, but not thyroglobulin ribonucleic acid levels in human thyroid follicular cells in vitro. 170 76

Isolated sheep thyroid follicles release specific insulin-like growth factor-binding proteins (IGFBPs). Since IGFBPs can modulate IGF bioactivity, at least in vitro, their presence in thyroid tissue may influence synergistic interactions between TSH and endogenous IGF-I or -II which are known to control both thyroid growth and function. We have examined the hormonal control of IGFBP release in relation to iodine organification. Sheep thyroid follicles were isolated by incubation with collagenase and differential centrifugation, grown in Coon's modified Ham's F12M medium with the addition of transferrin, glycylhistidyl-lysine, somatostatin (3H), TSH, cortisol and insulin (6H), and maintained in OH (hormone-free) or 3H medium with or without further supplements for 48 h. Conditioned culture medium was separated by 8% sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis, transferred to nitrocellulose and incubated with 125I-labelled IGF-II followed by autoradiography (ligand blot). Additionally, the radioactive bands were cut from the filters and quantified by gamma-spectrometry. Iodine organification was assessed by incubation of follicles with 10(6) c.p.m. Na125I for 3 h before washing, solubilization in 0.1 mol NaOH/l and the precipitation of organified radioisotope with 10% (v/v) trichloroacetic acid. Cells conditioned in OH or 3H medium released specific IGFBPs of 46, 34, 28 and 19 kDa on ligand blot analysis. The proteins of 34 and 19 kDa were immunopositive on Western blot analysis using anti-bovine IGFBP-2 antiserum. The 46-kDa IGFBP was retained by Concanavalin A-Sepharose chromatography and demonstrated to be glycoprotein. This is probably ovine IGFBP-3. The addition of TSH, or TSH plus cortisol to OH or 3H medium significantly decreased the 125I-labelled IGF-II associated with the 34- and 28-kDa IGFBP species. All IGFBP species were substantially reduced in 6H medium, which was predominantly due to the effects of TSH and cortisol. When total 125I-labelled IGF-II associated with IGFBPs was considered, a significant (P less than 0.01) inverse correlation existed between IGFBP activity and iodine organification in the same cultures; the latter being greatest in OH or 3H medium supplemented with TSH and cortisol. None of these hormone additions altered the endogenous release of IGF-II by the cells. These results suggest that endogenous IGFs, under hormonal control, may modulate the action of endogenous IGF in the regulation of thyroid function.
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PMID:Hormonal regulation of insulin-like growth factor (IGF)-binding proteins secreted by isolated sheep thyroid epithelial cells: relationship with iodine organification. 171 78

Six insulin-like growth factor binding proteins (IGFBP) have been identified in the conditioned medium from sheep thyroid cells cultured under serum-free conditions. IGFBPs of 32, 28, 23 and 19 kDa were secreted by cells cultured for 14 days in serum-free and hormone-free medium. The constitutive secretion of IGFBP was inhibited by thyrotropin (TSH, 0.3 mU per mL). The effect was most marked on the secretion of the 28 kDa BP. High insulin concentrations stimulated the secretion of this IGFBP. The stimulatory effects of insulin were inhibited by TSH. Growth hormone treatment decreased the secretion of the 28 kDa protein. Tetradecanoylphorbol-13 acetate (TPA) and epidermal growth factor (EGF) both of which stimulate thyroid cell growth but inhibit differentiated function, markedly stimulated IGFBP secretion and induced the appearance of a 46 and a 150 kDa IGFBP. The effects of EGF and TPA were not identical. A rat IGFBP-2 cDNA reacted with sheep thyroid RNA of approximate size 1.6 kb. TPA treatment increased IGFBP-2 mRNA. Other hormones used to enhance differentiation and growth in thyroid cells in culture i.e. transferrin, somatostatin, cortisol and glycyl-histidyl-lysine acetate had no marked effects on IGFBP secretion nor on TSH-dependent, insulin-mediated iodide uptake and organification and cell growth. We show a correlation between secretion of high molecular weight IGFBP with enhanced growth but decreased function. Conversely, we find a correlation between decreased secretion of the 28 kDa BP and increased growth and function.
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PMID:Thyrotropin inhibits while insulin, epidermal growth factor and tetradecanoyl phorbol acetate stimulate insulin-like growth factor binding protein secretion from sheep thyroid cells. 172 84

TSH as well as alpha-subunit, secretion has been shown to decrease after the administration of the somatostatin analog octreotide acetate (SMS 201-995). We have studied a 59-yr-old, male patient with a TSH- and gonadotropin-secreting tumor who, because of severe cardiomyopathy, was treated with long-term somatostatin analog rather than surgical resection of the pituitary tumor. Thirteen weeks of treatment with thrice daily sc injection of 100 micrograms octreotide acetate resulted in decreased TSH and alpha-subunit secretion, normal serum thyroid hormone levels, reduction in LH and testosterone level, and significant tumor size reduction. Long-term treatment for 51 weeks has not been associated with any significant side effects. We have shown that octreotide acetate may be a therapeutically valuable modality for certain patients with neoplastic inappropriate secretion of TSH (NIST). A probable effect of octreotide acetate on neoplastic gonadotropes, as evidenced by the reduction of the LH level with a concomitant decrease in testosterone level, is, likewise, suggested.
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PMID:Reduction in size of a thyrotropin- and gonadotropin-secreting pituitary adenoma treated with octreotide acetate (somatostatin analog). 174 May 6

It has been demonstrated that nerve fibres storing immunoreactivity of vasoactive intestinal polypeptide, peptide histidine iso-leucine, neuropeptide Y, substance P, calcitonin gene-related peptide, galanin, and cholecystokinin exists in the thyroid, though the content of these neuropeptides is lower in the thyroid than in other organs, like in the gut. Furthermore, the parafollicular C-cells have been shown to harbour several different peptides: calcitonin, somatostatin, calcitonin gene-related peptide, gastrin-releasing peptide, katacalcin and helodermin. In addition, other regulatory peptides like atrial natriuretic hormone, growth factors, and cytokines are also produced in the thyroid. This review summarizes today's knowledge on the effects of these peptides on thyroid hormone secretion and their possible role in thyroid physiology. So far, functional studies have failed to establish any convincing effect of substance P, calcitonin gene-related peptide, galanin and cholecystokinin on basal or TSH-stimulated thyroid hormone secretion. In contrast, vasoactive intestinal peptide has convincingly been demonstrated to stimulate thyroid hormone secretion, and neuropeptide Y to potentiate the inhibitory action of noradrenaline on TSH-induced thyroid hormone secretion. This suggests that these two neuropeptides are involved in the intrathyroidal neural regulation of thyroid function. Moreover, the C-cell peptides somatostatin, calcitonin, calcitonin gene-related peptide, and katacalcin seem to be involved as inhibitors of thyroid hormone secretion, whereas both gastrin-releasing peptide and helodermin stimulate thyroid hormone secretion. Atrial natriuretic hormone and growth factors, and cytokines seem to inhibit thyroid hormone secretion. Hence, studies undertaken so far suggest a local intrathyroidal peptidergic regulatory concept, the exact role of which remains to be established.
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PMID:Regulatory peptides in the thyroid gland--a review on their localization and function. 182 1

An invasive TSH-secreting adenoma inducing mild hyperthyroidism was diagnosed in a 16-year-old male. Initial surgical treatment led to a temporary clinical and biological improvement. Recurrence of the thyrotoxicosis was treated with the somatostatin analogue, SMS 201-995 (octreotide) with normalization of the serum thyroid hormone levels with a dose of 200 micrograms per day. With immunoelectron microscopy, the tumour cells appeared poorly granulated with small secretory granules located at the periphery of the cells; only part of those were immunoreactive with an anti-TSH beta monoclonal antibody. No specific TRH binding site was found in a tumour membrane preparation. By quantitative autoradiography, somatostatin specific binding sites were as numerous in the TSH-secreting tumour as in control GH-secreting tumours. Binding kinetics and guanosine triphosphate dependency of the binding were equivalent in the TSH and GH tumours tested. Although all of the tumour cells displayed the same ultrastructural features, some were non-immunoreactive, suggesting that they could secrete an altered form of TSH. The absence of TRH receptors in the tumour cells is in accordance with previous reports on this type of tumour. We confirm the efficiency of octreotide treatment in this case of neoplastic TSH inappropriate secretion. The therapeutic effect of octreotide goes along with the presence of a high density of guanine nucleotide-dependent somatostatin binding sites in the tumour cells.
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PMID:A human TSH-secreting adenoma: endocrine, biochemical and morphological studies. Evidence of somatostatin receptors by using quantitative autoradiography. Clinical and biological improvement by SMS 201-995 treatment. 185 93

Cholinergic pathways play an important role in the regulation of GH secretion. To assess their participation in GH feedback, we investigated the effect of pyridostigmine (an acetylcholinesterase inhibitor) on plasma GH responses to GH-releasing hormone (GHRH) plus TRH, insulin hypoglycemia, and arginine as well as on the inhibition of these responses by exogenous GH. The GH response to each stimulus was inhibited by an infusion of GH (0.55 micrograms/m2/min), started 4 h earlier. Pyridostigmine (120 mg, orally), administered 30 min before the stimulus, enhanced GH responses to GHRH and insulin during both saline and GH infusions. However, GH responses during combined administration of pyridostigmine and GH were less than those during pyridostigmine alone. GH responses to arginine, in contrast, were not affected by pyridostigmine in either the absence or presence of exogenous GH. TSH responses to TRH were unaltered by either GH or pyridostigmine. Pyridostigmine enhancement of GH responses to a maximally stimulatory dose of GHRH suggests that its effect is exerted by inhibition of somatostatin release. The lack of effect of pyridostigmine on plasma GH responses to arginine suggests that arginine and pyridostigmine increase GH secretion through a common pathway. The enhancement by pyridostigmine of GH responses in both the presence and absence of exogenous GH suggests that exogenous GH and pyridostigmine exert their discordant effects on GH secretion through independent mechanisms.
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PMID:The role of the cholinergic pathway in growth hormone feedback. 190 84

We studied the effect of histamine on serum prolactin and thyrotropin (TSH) levels in male rats with anterolateral hypothalamic deafferentation of hypothalamic connections or anterolateral cut (ALC). The success of ALC was confirmed by immunohistochemistry of somatostatin (SRIF) in the medial basal hypothalamus. ALC did not affect basal prolactin or TSH levels. Thyrotropin-releasing hormone (TRH, 200 ng/rat, i.p.) did not affect prolactin secretion either in sham-operated or ALC rats. In sham-operated rats intracerebroventricularly administered histamine increased significantly prolactin levels. Hypothalamic deafferentation abolished the effect of histamine on prolactin levels. TRH increased significantly serum TSH levels both in sham-operated controls and ALC rats. In the latter, however, the TSH-secretory response to TRH was significantly (p less than 0.05) larger compared to the controls. Intracerebroventricularly infused histamine (2 micrograms/rat) did not change the TRH-induced TSH secretion in either group of rats. These results show that (1) the effect of histamine on prolactin secretion is mediated through nerve tracts which are destroyed by ALC, and (2) cutting of afferent TRH (through sensitization) and SRIF fibers (through lacking inhibition) entering medial basal hypothalamus may both contribute to the enhanced TSH response to exogenous TRH.
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PMID:Anterolateral hypothalamic deafferentation inhibits histamine-induced prolactin secretion and potentiates TRH-induced thyrotropin secretion in male rats. 194 13

Somatostatin (SRIF) inhibits calcitonin and T3-T4 secretion in thyroid. We have investigated the in vitro effect of SRIF on the basal and TSH induced [3H]thy incorporation, thyroglobulin (tgb) RNA and cAMP level in follicular cells, isolated from normal and adenomatous human thyroids. [3H]thy uptake has been evaluated as TCA-precipitable material in 2, 4, 8, 24 h incubated follicles and 24 h incubated adherent cells. Tgb RNA has been quantified with cytoplasmic dot blot hybridization and cAMP level with RIA method. SRIF reduces basal and TSH-induced [3H]thy in both suspension follicles and epithelial adherent cells. However it does not modify tgb RNA nor cAMP levels in incubated follicles. These data suggest a direct antiproliferative effect of SRIF on human thyroid.
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PMID:[Effects of somatostatin on human thyroid folliculi in vitro]. 196 42


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