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)

This article reviews the biological signals and factors involved in normal and pathological thyrocyte proliferation. The role of thyrotropin, cyclic adenosine 3'5'-monophosphate and hormones of anterior pituitary and placental origin are discussed. The effects on thyroid growth of insulin and insulin-like growth factors, epidermal growth factor and fibroblast growth factor are analyzed, as well as those of metabolites of arachidonic acid, iodide, neuropeptides like somatostatin, calcium metabolism and melatonin. Thyroid growth is also under the control of the sympathetic and parasympathetic nerves of cervical sympathetic and vagal origin, respectively. Involvement of growth-affecting factors that contribute as risk factors for thyroid tumorigenesis, and the pathological immunoglobulins stimulating or inhibiting thyroid growth are reviewed. The picture that emerges underlines the complexity of the regulating phenomena controlling thyroid growth.
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PMID:Thyroid growth-stimulating and growth-inhibiting factors. 791 49

1. The sympathetic superior cervical ganglia (SCG) provide innervation to the pineal gland and median eminence through the internal carotid nerve and to the thyroid and parathyroid glands through the external carotid nerve. 2. Postsynaptic activation in median eminence nerve endings shortly after superior cervical ganglionectomy (SCGx) was accompanied by a depression of LH and FSH release and by a 3-5 day delay in rat estrous cyclicity. A decrease in TSH and GH release and an increase in ACTH and prolactin release were also found. These effects were accompanied by a) an increase in medial basal hypothalamic (MBH) LHRH, TRH and GHRH, b) a decrease in MBH somatostatin, AVP and CRH, and c) a normal adenohypophyseal response to hypophysiotropic hormones. Neurohypophyseal AVP release decreased during degeneration of sympathetic nerve terminals in the neurohypophyseal lobe after SCGx. The effects were generally mediated by alpha 1-adrenoceptors and were pineal gland. 3. In thyroid and parathyroid tissue the following events were observed during the wallerian degeneration phase after SCGx: a) alpha 1-adrenoceptor inhibition of thyroxine (T4) release, b) alpha 1-adrenoceptor inhibition, together with beta-adrenoceptor stimulation, of calcitonin release, and c) alpha 1-adrenoceptor inhibition of parathyroid hormone release. Thyroid sympathetic nerves also modulate slow phenomena such as compensatory thyroid growth after partial thyroidectomy. 4. In rats subjected to cholinergic decentralization of the thyroid gland, a decrease of plasma T4 and an increase of plasma TSH, as well as an impaired goitrogenic and thyroid compensatory response were detectable. The calcitonin and PTH response to changes in calcium levels increased after regional parasympathetic denervation. 5. The results indicate that cervical autonomic nerves constitute a parallel pathway through which the brain communicates with the endocrine system.
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PMID:Peripheral neuroendocrinology of the cervical autonomic nervous system. 808 Dec 83

Thyroid hormones are important to growth in mammals and have been shown to rapidly stimulate the rate of GH gene transcription. In this study, we investigated whether thyroid hormones modulate GH secretion through their effects on the gene expression of GRF, somatostatin (SS), GRF receptor, and receptor subtype 2 for SS (SSTR2). Male adult Sprague-Dawley rats were rendered hypothyroid with a single injection of propylthiouracil followed by methimazole in drinking water (0.02%) for 1 day to 12 weeks. Total RNA extracted from the anterior pituitary and hypothalamus was analyzed by Northern hybridization. GH messenger RNA (mRNA) level in the anterior pituitary was significantly reduced in the hypothyroid animals (P < 0.0001 vs. controls for all treatment duration > or = 1 week). An increase in hypothalamic GRF mRNA level, by 2- and 4-fold, respectively, was seen after 3 and 12 weeks of antithyroid treatment (both P < 0.001 vs. controls). Hypothalamic GRF content, studied in 12-week hypothyroid rats only, was decreased compared with controls (P < 0.05). A reduction in pituitary GRF receptor mRNA level was observed after 1 week of antithyroid treatment (P < 0.01 after 1 week, P < 0.001 after 3 weeks). Total hypothalamic SS content and SS mRNA level in hypothalamic fragments consisting predominantly of the paraventricular and periventricular nuclei became significantly decreased (P < 0.05 and P < 0.005 respectively) after 12-weeks of antithyroid treatment. The reduction in SS gene expression in the periventricular nuclei was confirmed by in situ hybridization. No significant change in the mRNA level of pituitary SSTR2 was observed up to 12 weeks of antithyroid treatment. In conclusion, we have demonstrated a reduction in the gene expression of GRF receptor and SS in the hypothyroid rat. Our results suggest that the changes in hypothalamic GRF and SS gene expression in hypothyroid rats may be compensatory in nature and are likely to be secondary to the reduction in GH synthesis and secretion in these animals. The reduction in basal and GRF-stimulated GH secretion in hypothyroidism can be explained by the observed reduction in GH and GRF receptor gene expression.
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PMID:Gene expression of hypothalamic somatostatin, growth hormone releasing factor, and their pituitary receptors in hypothyroidism. 859 84

Uncontrolled study has demonstrated the usefulness of somatostatin in the treatment of mild Graves' ophthalmopathy (GO). We performed a prospective study to evaluate the usefulness of somatostatin as compared to corticosteroid in the treatment of moderately severe GO. All patients were rendered euthyroid and observed for 3 months to exclude spontaneous improvement without active treatment. They were randomized to receive either somatostatin (SS, octreotide 200 micrograms q8h subcutaneously, n = 8) or corticosteroid (CS, prednisone 1 mg/kg/day in decreasing doses, n = 10). Assessments of soft tissue inflammation, exophthalmos, palpebral aperture, intraocular pressure, diplopia, cornea, and visual acuity were made every 4 weeks for 3 months. MRI of the orbit was performed before and after treatment. Both SS and CS therapy decreased the palpebral aperture and activity score after 3 months (p < 0.05), but those treated with CS had a lower activity score after treatment when compared to SS [2.5 (1-7) v.s. 3.5 (0-4), median (range), p < 0.05]. Only CS, but not SS, was able to reduce intraocular pressure and muscle size as documented by MRI, but no significant reduction in proptosis was observed in either group. Also, patients' self-assessments of the eye changes after treatment were similar between the two groups. Both groups showed significant elevation of urinary glycosaminoglycan (GAG) excretion before therapy (SS 24.6 +/- 10.8; CS 27.8 +/- 11.4 mg/24 h), which was reduced after treatment (SS 12.5 +/- 7.3; CS 10.8 +/- 6.3 mg/24 h, p < 0.05). However, no significant correlation could be observed between the degree of GAG reduction and the clinical outcome of the patients. In conclusion, the long acting SS octreotide was effective in reducing soft tissue inflammation and providing symptomatic relief in GO but not as effective as corticosteroid in reducing muscle size. In view of the minimal side-effects and similar efficacy as compared to corticosteroid in patients with minimal extraocular muscle enlargement, it is suggested that a trial of SS may be considered in selected patients with GO.
Thyroid 1996 Oct
PMID:The effect of somatostatin versus corticosteroid in the treatment of Graves' ophthalmopathy. 922 22

Thyroid associated ophthalmopathy (TAO) is a disorder involving the soft tissues and extraocular muscles of the orbit seen mainly in cases of Graves' disease. Although an immunogenic pathogenesis has been proposed, the actual mechanisms of the in vivo retrobulbar involvement are not well defined. The recent introduction of the 111In-labeled somatostatin analog, octreotide, which can bind in vivo to the cell membrane of activated lymphocytes expressing somatostatin receptors, has provided a new investigational tool for diseases with a presumed immunological background. Based on this property, octreotide scans can be expected to be positive in cases of immunological disease showing tracer accumulation within affected sites. The aim of this study was to evaluate the utility of scintigraphic imaging with octreotide of the retrobulbar space in cases of TAO, including sequential studies of patients undergoing immunosuppressive therapy. We studied a series of 51 patients who had Graves' disease with varying degrees of TAO. Nine patients had received immunosuppressive therapy. The degree of orbital inflammation was classified according to the clinical activity score of Mourits. Both planar and tomographic imaging of the orbit were carried out using 111 MBq of the 111In-labeled octreotide (OctreoScan) 2 h after tracer injection. A significant tracer accumulation in the retrobulbar space was seen in all 20 patients with a high activity score, in 8 of 16 cases with a negative score, and in 11 of 20 cases with an intermediate Mourits' score. In cases of persistent eye disease in spite of immunosuppressive therapy, the octreotide scan remained positive. Successful therapy either with prednisolone, external radiation, or i.v. immunoglobulins showed a significant diminution of tracer uptake after finishing the therapeutic regime. Three-dimensional reconstruction of the images also revealed a significant tracer accumulation in the areas of the lacrimal gland, the nasal region, and the pituitary. Controls cases (n = 30) showed no uptake in the orbital region. We conclude that 111In octreotide scintigraphy is an objective method that identifies patients with active inflammatory eye disease, i.e., having significant tracer uptake in the retrobulbar space. This uptake appears to reflect an immunological process, since immunosuppressive therapy will significantly decrease tracer accumulation.
Thyroid 1997 Feb
PMID:Evaluation of immunological mechanisms mediating thyroid-associated ophthalmopathy by radionuclide imaging using the somatostatin analog 111In-octreotide. 934 89

We present a 32-year-old male with a thyrotropin (TSH)-secreting pituitary microadenoma with normal alpha-subunit (SU) and/or alpha-SU/TSH molar ratio. An interesting feature of this patient is that the size of the pituitary tumor remained unchanged during a 6-year follow-up without treatment. The tumor was clearly visualized with somatostatin receptor imaging, indicating that it was somatostatin receptor-positive. Subcutaneous injection of 100 microg octreotide acetate three times daily resulted in significant reduction of TSH and free thyroid hormones 6 weeks after initiation of treatment. However, tumor size was not changed 3 months after initiation of octreotide therapy and thyroid hormones, but not TSH level, eventually increased in spite of increasing the octreotide dosage up to 600 microg/day. This led to discontinuation of treatment. The patient responded only temporarily to octreotide in spite of somatostatin receptors. This case further demonstrates that a normal alpha-SU and/or alpha-SU/TSH molar ratio cannot exclude the possibility of a TSH-secreting pituitary adenoma.
Thyroid 1997 Jun
PMID:A case of thyrotropin-secreting pituitary microadenoma with normal thyrotropin alpha-subunit level. 922 17

We report here an unusual case of association between thyrotropin (TSH)-secreting pituitary adenoma and papillary thyroid carcinoma in a young female patient. Serum TSH levels did not significantly change after both stimulatory (thyrotropin-releasing hormone [TRH], domperidone) and inhibitory (bromocriptine levotriiodothyronine, [LT3], levothyroxine [LT4], LT4 plus LT3) tests, while a 67% decrease of serum TSH levels was obtained after acute administration of a somatostatin analog (SMS 201-995, 100 microg s.c.). Serum alpha-subunit levels and the alpha-subunit/TSH molar ratio were clearly elevated. Magnetic resonance imaging (MRI) revealed the presence of a pituitary adenoma (1 cm in diameter). Pitfalls arising from the failure to inhibit TSH secretion in a patient thyroidectomized for papillary cancer are discussed.
Thyroid 1998 Feb
PMID:Unusual association between a thyrotropin-secreting pituitary adenoma and a papillary thyroid carcinoma. 951 Jan 28

1. Regulation of pulsatile secretion of growth hormone (GH) relies on hypothalamic neuronal loops, major transmitters involved in their operation are growth hormone releasing hormone (GHRH) synthetized mostly in arcuate nucleus (ARC) neurons, and somatostatin (SRIH), synthetized both in hypothalamus periventricular (PVe) and ARC neurons. 2. Neurons synthetizing both peptides can inhibit each other in a reciprocal manner. Other neuropeptides synthetized in ARC neurons, such as galanin, or in ARC interneurons, such as neuropeptide Y (NPY), are able to modulate synthesis and release of GHRH and SRIH into the hypothalamohypophyseal portal system. 3. In addition, the hitherto uncharacterized endogenous ligand of the recently cloned growth hormone releasing peptide receptor, expressed mostly in the ARC, triggers GH release, presumably by actions on ARC interneurons. 4. Thyroid, gonadal, and adrenal steroid hormones also affect the GHRH-SRIH balance; a differential distribution of sex steroid receptors in the ARC and the PVe is likely to account for the different pattern of GH secretion in male and female animals. 5. Growth hormone itself is able to inhibit the amplitude of GH secretory episodes and to increase their frequency, by entering the brain (presumably by receptor-mediated internalization at the level of the choroid plexus) and acting subsequently on ARC neurons. 6. At the pituitary level, major neurotransmitters regulating GH cells act on receptors of the VIP/PACAP/GHRH family and of the somatostatin family, in particular, sst2 and sst3. Those are coupled to accumulation of cAMP as a second messenger. 7. In addition, patch-clamp experiments and measurement of intracellular Ca2+ indicate that GH cells present characteristic, GHRH-dependent, but self-maintained Ca2+ spikes and [Ca2+]i transients, which reflect adaptive mechanisms to constraints of episodic release. 8. Recent data on transcription factors affecting GH gene expression and somatotrope differentiation are also summarized. 9. Regulation and differentiation of somatotropes also depend upon paracrine processes within the pituitary itself and involve growth factors and several neuropeptides, for instance, vasoactive intestinal peptide, angiotensin 2, endothelin, and activin. 10. Finally, characteristic changes occur in the GH secretory pattern under discrete, pathological conditions, such as abnormal growth and dwarfism, diabetes, and acromegaly, as well as during inflammatory processes.
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PMID:Hypothalamic and hypophyseal regulation of growth hormone secretion. 952 32

Thyroid-stimulating hormone (TSH) secreting pituitary adenoma is a rare but important cause of thyrotoxicosis. It poses a challenge for both diagnosis and management. We report the case of a young Chinese man presenting with thyrotoxicosis, complicated by congestive heart failure, secondary to a TSH secreting pituitary adenoma. The case illustrates the importance of prompt diagnosis and allows discussion of both medical and surgical management, including the use of a long-acting somatostatin analogue.
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PMID:TSH secreting pituitary adenoma: a rare cause of thyrotoxicosis. 953 75

Recent studies have shown successful therapy with the long-acting somatostatin (SM) analogues octreotide and lanreotide in patients with thyroid eye disease (TED). In one such study it was also found that response to low-dose octreotide treatment (300 microg) in these patients was correctly predicted by [111In-DTPA-D-Phe1]-octreotide scintigraphy and concluded that this parameter should be used as a predictive test of the effectiveness of treatment with nonradioactive octreotide. It has also been suggested that octreoscan-111 may be seen as a parameter of disease activity in TED. However, it remains to be clarified whether octreoscan-111 predicts the therapeutic outcome better than the clinical activity score, or magnetic resonance imaging (MRI) or finally measurement of glucosaminoglycan (GAG) in the plasma and/or urine. The exact mechanism of action of SM analogues has not yet been fully clarified. Three explanations may be offered. First, SM suppresses insulin-like growth factor 1 (IGF-1) activity and inhibits IGF-1-mediated effects. A second possible mechanism could be the direct inhibition of the release of cytokines from T-lymphocytes, and finally, SM analogues may act on target cells through specific cell surface receptors. In view of the encouraging therapeutic results reported thus far in several studies, SM analogues may provide a valuable therapeutic alternative to corticosteroids, especially in patients who cannot tolerate the latter. However, further prospective, placebo-controlled studies with a large number of patients are needed before we can reach final conclusions.
Thyroid 1998 May
PMID:Somatostatin analogues in the treatment of thyroid eye disease. 962 41


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