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)

Specific somatostatin (SRIH) receptors on human pituitary adenoma cell membranes were characterized using [125I]Tyr11-SRIH as the radioligand. Specific binding of [125I] Tyr11-SRIH to adenoma cell membranes reached a steady state within 30 min at 25 C, and semilogarithmic analysis of the data revealed that the rate of the binding was linear at 25 C with a t1/2 of 13.2 min. Specific binding increased linearly with 5-160 micrograms plasma membrane protein. SRIH-14 and SRIH-28 inhibited [125I]Tyr11-SRIH binding to adenoma cell membranes with ID50S of 0.32 and 0.50 nM, respectively, while secretin, glucagon, gastrin, cholecystokinin-8, bombesin, TRH, LHRH, human GH-releasing factor-(1-44)-NH2, D-Ala2-met-enkephalin, gamma-aminobutyric acid and taurine did not significantly inhibit binding. All of 13 GH-secreting adenomas investigated had specific and high affinity SRIH receptors, with a dissociation constant (Kd) of 0.80 +/- 0.15 nM (mean +/- SEM) and a maximal binding capacity (Bmax) of 234.2 +/- 86.9 fmol/mg protein (mean +/- SEM). Among five of the nonsecreting pituitary adenomas examined, two had SRIH receptors with Kd values of 0.18 and 0.32 nM and Bmax values of 17.2 and 48.0 fmol/mg protein, respectively. In the remaining three, SRIH receptors were not detected. These results indicate that GH-secreting adenomas as well as some nonfunctioning adenomas have specific SRIH receptors, and hence, the function of the adenomas could be altered by SRIH.
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PMID:Specific somatostatin receptors on human pituitary adenoma cell membranes. 286 81

We have studied the in vitro TSH secretion and the adenylate cyclase (AC) activity of a human pituitary adenoma surgically removed from a hyperthyroid patient showing high serum TSH levels. The tumor appeared almost homogeneously constituted by cells positive for an anti-TSH-beta antiserum and showing the ultrastructural characteristics of the adenomatous thyrotrophs. Adenoma fragments released in vitro a large amount of TSH (148.4 microU/mg prot/30 min), alpha-subunit (35.5 ng/mg prot/30 min) and TSH-beta (10.1 ng/mg prot/30 min). The effects of somatostatin (GHRIH) and dopamine (DA) on the hormone release have been tested in vitro. Both agents markedly inhibited the release of intact TSH and TSH-beta whereas the release of alpha-subunit was less affected. The two agents were effective at concentrations higher than 10(-8)M. The ability of GHRIH and DA in modulating the AC activity was investigated in membrane fraction preparations. GHRIH inhibited AC at concentrations higher than 10(-7)M. The maximal inhibition was 32% at 10(-5)M. Conversely, DA slightly stimulated AC activity. This effects was not mimicked by the dopaminergic ergot CH 29-717, which was completely ineffective on the enzyme. These results suggest that: 1) in this TSH-secreting pituitary adenoma a normal secretory response to the inhibiting agents (GHRIH and DA) is present; 2) different mechanisms of transduction of the GHRIH and DA signals (cAMP dependent and cAMP independent) could be operating in this tumor.
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PMID:In vitro studies on TSH secretion and adenylate cyclase activity in a human TSH-secreting pituitary adenoma. Effects of somatostatin and dopamine. 286 99

The plasma GH response to somatostatin (SRIH) infusion and SRIH receptors in pituitary adenoma cell membranes were investigated in six acromegalic patients. Infusion of 0.3 and 1.0 microgram/kg . h SRIH increased plasma SRIH concentrations in these patients in a dose-related manner. In five of the six patients, mean plasma GH levels decreased to 65.5 +/- 5.0% (+/- SEM) and 43.7 +/- 3.1% of the basal level when 0.3 or 1.0 microgram/kg . h SRIH was infused, respectively. In the remaining patient, plasma GH levels did not change, even when a larger dose of SRIH was infused. High density and specific SRIH receptors, with a mean dissociation constant of 0.92 +/- 0.17 nM and a mean maximal binding capacity of 523.8 +/- 174.6 fmol/mg protein, were identified in GH-secreting adenomas from the five SRIH-responsive patients. On the other hand, in the adenoma from the SRIH-nonresponsive patient, the maximal binding capacity (40.5 fmol/mg protein) was as low as those of nonfunctioning adenomas, as reported previously (undetectable to 48.0 fmol/mg protein). We conclude that the differential responses of plasma GH to SRIH in acromegalic patients may be related to variations in the binding capacity for SRIH in adenoma cell membranes.
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PMID:Plasma growth hormone responses to somatostatin (SRIH) and SRIH receptors in pituitary adenomas in acromegalic patients. 286 49

We have evaluated the role of cellular Ca2+ transport associated with stimulus-secretion coupling in prolactin (PRL) producing rat pituitary adenoma cells (GH3 cells). The action of different substances, known to modify PRL secretion, on release of 45Ca2+ from preloaded cells were examined. Surface-bound 45Ca2+ was removed by pretreatment with trypsin in EDTA buffer. During the first 6 min, basal efflux of 45Ca2+ occurred at a constant rate (0.24 min-1) at 37 degrees C. Addition of TRH (5 X 10(-7) M) resulted in an immediate enhancement of 45Ca2+ release representing about 20% of the remaining cellular 45Ca2+. In the same experiments PRL secretion increased by 45%. The EDTA in the external medium reduced the basal rate of 45Ca2+ release by 60%, but did not apparently affect the TRH-stimulated release. Somatostatin (10(-6) M) and verapamil (5 X 10(-5) M) inhibited both basal and TRH-stimulated PRL secretion, whereas high extracellular concentration of K+ (5 X 10(-2) M) had a stimulatory effect. However, neither of these treatments changed cellular 45Ca2+ release. Interference with energy-dependent Ca2+ transport by using metabolic inhibitors (iodoacetate, 6 X 10(-3) M; and antimycin, 2 X 10(-6) M) or by replacing Na+ in the medium by choline or by lowering the incubation temperature from 37 to 25 degrees C, had no effect on TRH-stimulated 45Ca2+ release although basal and TRH-stimulated PRL secretion were reduced. Thus, TRH apparently releases 45Ca2+ from calcium binding sites in the cell membrane.
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PMID:On the functional relationship between 45Ca2+ release and prolactin secretion in cultured rat pituitary tumour (GH3) cells. 287 12

Membrane electrical properties and the response to somatostatin were examined in dissociated human pituitary adenoma cells that secrete growth hormone (GH). Under current clamp condition with a patch electrode, the resting potential was -52.4 +/- 8.0 mV, and spontaneous action potentials were observed in 58% of the cells. Under voltage clamp condition an outward K+ current, a tetrodotoxin-sensitive Na+ current, and a Ca2+ current were observed. Cobalt ions suppressed the Ca2+ current. The threshold of Ca2+ current activation was about -60 mV. Somatostatin elicited a membrane hyperpolarization associated with increased membrane permeability in these cells. The reversal potential of somatostatin-induced hyperpolarization was -78.4 +/- 4.3 mV in 6 mM K+ medium and -97.2 +/- 6.4 mV in 3 mM K+ medium. These reversal potential values and a shift with the external K+ concentration indicated that membrane hyperpolarization was caused by increased permeability to K+. The hyperpolarized membrane potential induced by somatostatin was -63.6 +/- 5.9 mV in the standard medium. This level was subthreshold for Ca2+ and Na+ currents and was sufficient to inhibit spontaneous action potentials. Hormone secretion was significantly suppressed by somatostatin and cobalt ions. Therefore, we suggest that Ca2+ entering the cell through voltage-dependent channels are playing an important role for GH secretion and that somatostatin suppresses GH secretion by blocking Ca2+ currents. Finally, we discuss other possibilities for the inhibitory effect of somatostatin on GH secretion.
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PMID:Hyperpolarization of the membrane potential caused by somatostatin in dissociated human pituitary adenoma cells that secrete growth hormone. 287 59

We report the first documentation of GHRH production by a tumour associated with proven multiple endocrine neoplasia (MEN). A 30-year-old woman had hypoglycaemia, hyperparathyroidism, and pituitary adenoma with hyperprolactinaemia. Serum growth hormone elevation was attributed to hypoglycaemia but plasma GHRH was elevated. Subtotal pancreatectomy revealed multiple endocrine tumours and nesidioblastosis. Immunohistochemistry demonstrated insulin, glucagon, and somatostatin in several tumours. GHRH was localized in the largest one and was released from that tumour in vitro. Post-operative plasma GH returned to normal. Excess secretion of humoural factors by one tumour may stimulate growth of other tumours in MEN syndromes. The prevalence of GHRH in MEN-I tumours remains to be established.
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PMID:Pancreatic endocrine tumour producing growth hormone-releasing hormone associated with multiple endocrine neoplasia type I syndrome. 288 80

Thyrotropic pituitary adenoma is a rare disease fortunately diagnosed with increasing frequency. Its originality lies in the fact that it occurs in two very different pathological contexts. The first form raises few problems: the occurrence of a pituitary tumoral syndrome in a patient with hypothyroidism, even of relatively short duration, should suggest the diagnosis. In such cases of reactive thyrotropic adenoma, simple correction of the hypothyroidism by replacement therapy seems to be capable not only of curing the thyroid disorder and lowering TSH values, but also of promoting regression of the pituitary tumour. Primary autonomous adenoma responsible for TSH hypersecretion followed by thyrotoxicosis belongs to the realm of inappropriate TSH secretion, and it should be diagnosed whenever high, or even normal (at least non-suppressed). TSH levels coexist with peripheral hyperthyroidism. As a rule, the presence of a pituitary tumour differentiates this adenoma from non-tumoral inappropriate TSH secretion due to resistance to thyroid hormones. Primary thyrotropic pituitary adenoma is treated by surgery. In case of failure or relapse, radiotherapy or medical treatment with a dopaminergic agonist or a long-acting somatostatin analogue may be considered.
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PMID:[Thyrotropic pituitary adenoma. Clinical aspects, course and treatment]. 295 27

A 54 year old woman suffered from acromegaly due to a pancreatic islet cell tumour producing GHRH. The tumour was demonstrated on CT scan. The diagnosis was established from elevated plasma levels of GHRH, GH and prolactin, and by the lack of signs of a pituitary adenoma in trans-sphenoidal surgery. Acromegaly was cured by tumour removal. Light microscopically, the tumour showed a medullary and microlobular pattern. The cells were large and often cuspidal. Small granules were found in semi-thin sections. Small aggregations of amyloid fibres were seen, mostly around capillaries. Immunocytochemistry revealed GHRH, NSE, neurotensin, serotonin, VIP and PP. S 100 was positive only in nerve fibres. Staining for GH, ACTH, calcitonin, alpha-HCG, beta-HCG, insulin, glucagon, gastrin, substance P, bombesin and somatostatin was negative. Ultrastructure showed oval partly lobulated nuclei with small nucleoli, moderate amounts of rough endoplasmic reticulum, many free ribosomes, some large Golgi fields and small numbers of secretory granules measuring 150 nm or, in a few cells, 650 nm. Only 4 other cases of pancreatic endocrine tumours causing acromegaly by ectopic GHRH secretion are described in the literature and these were similar to our case in many respects.
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PMID:Morphology of a GHRH producing pancreatic islet cell tumour causing acromegaly. 301 79

Acromegaly is caused by GH-secreting pituitary adenomas and, in rare cases, by ectopic production of GRH with resultant hypersecretion of GH. Important systemic manifestations include acral enlargement, swelling, disfigurement, glucose intolerance and diabetes, hypertension, nerve entrapment, arthropathy, and cardiac disease. Tumor-related major manifestations are visual impairment, oculomotor paralysis, and hypopituitarism. Morbidity is substantial, and mortality is increased. Diagnosis should be made as early as possible by measuring plasma GH after an oral glucose load and plasma somatomedin C levels. Assessment of a pituitary lesion is best made by CT scanning in the coronal plane. Therapy is mandatory and consists of surgical removal of the pituitary adenoma (usually by the transsphenoidal route) or of the ectopic source of GRH (carcinoids or islet cell tumors). Adjunctive radiation and/or drug therapy is often necessary if complete surgical ablation of the adenoma is not possible. Radiation therapy can be administered as conventional supervoltage x-ray treatment or in the form of heavy particle beams. Drugs effective in partially lowering GH levels are bromocriptine and (not yet released) somatostatin analogues. Long-term follow-up of treated patients is important to guard against recurrence, progression, or development of hypopituitarism.
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PMID:Acromegaly. 331 99

This paper reports the case of a 31-year-old woman with hyperthyroidism, increased TSH and thyroid hormone levels, evidence of a pituitary adenoma, hyperprolactinaemia, amenorrhoea, and galactorrhoea. Following trans-sphenoidal pituitary adenomectomy, mild hyperthyroidism and increased TSH and alpha subunit levels persisted, whereas hyperprolactinaemia, amenorrhoea, and galactorrhoea disappeared. Serum TSH levels were not affected by administration of TRH, metochlopramide, domperidone, l-dopa or somatostatin. Serum TSH chromatography showed a normal pattern. Following a second trans-sphenoidal pituitary adenomectomy and radiotherapy, hyperthyroidism disappeared, and the TSH and alpha subunit levels returned to normal. Light microscopy showed no specific TSH immunostaining although electron microscopy revealed numerous secretory granules alined along the plasma membrane. The post-operative follow-up confirmed the presence of a TSH-secreting pituitary adenoma associated to functional hyperprolactinaemia.
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PMID:Hyperthyroidism due to a thyroid-stimulating hormone (TSH)-secreting pituitary adenoma associated with functional hyperprolactinaemia. A case report. 342 60


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