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 study evaluated the effect of somatostatin on immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) secretion in vivo in rats and monkeys and on iPTH secretion in vitro by normal bovine parathyroid tissue and by a human parathyroid adenoma. Somatostatin infusion promptly (within 0.5 h) suppressed both iPTH and iCT in both species studied in vivo, the suppression being progressive during the infusion period. In in vitro studies, somatostatin caused significant dose-related decreases in basal, low Ca-stimulated, and high Ca-suppressed PTH secretion from normal bovine parathyroid tissue and from basal and low Ca-stimulated PTH secretion from a human parathyroid adenoma. Therefore, somatostatin 1) suppresses both PTH and CT secretion in vivo; 2) acts directly on the parathyroid cell and presumably directly on the C-cell also; 3) acts upon normal and adenomatous parathyroid tissue; 4) suppresses basal, low Ca-stimulated and high Ca-suppressed PTH secretion; and 5) has a dose-related effect. The possible role of somatostatin in the physiological control of PTH and CT secretion (and therefore in Ca homeostasis), and in the pathogenesis of abnormalities of Ca homeostasis, requires further evaluation.
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PMID:Effect of somatostatin on parathyroid hormone and calcitonin secretion. 10 71

High calcium leads to the secretion of calcitonin, and the administration of 1,25-dihydroxyvitamin D3 leads to a decreased transcription of the calcitonin gene. We now report the effect of chronic hypercalcemia, hypocalcemia, and vitamin D deficiency on calcitonin gene expression in vivo in the rat. Hypercalcemia was created by calcium infusions for 6 h, a high-calcium diet given to weanling rats for 3 weeks, and the transplantation of the Walker carcinosarcoma 256 cell line. Despite serum calcium as high as 22 mg/dl, there was no difference in calcitonin mRNA levels among these rats. The control genes studied, actin and somatostatin, which is specific for C cells in the thyroparathyroid tissue, also did not differ among the different groups of rats. Injected 1,25-(OH)2D3 decreased calcitonin mRNA levels at 6 h, as previously reported. Hypocalcemia, created by feeding diets deficient in calcium and vitamin D to weanling rats for 3 weeks, had no effect on calcitonin mRNA levels, in contrast to the large increases in PTH mRNA levels. These results demonstrate that calcitonin gene expression in vivo in the rat is regulated by administered 1,25-(OH)2D3 but not by changes in serum calcium.
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PMID:Regulation of calcitonin gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat. 136 Jul 44

Chromogranin-A (CgA) is an acidic soluble protein with a virtually ubiquitous occurrence in normal human neuroendocrine tissues. Of the many potential tissue sources of CgA immunoreactivity, which contribute to basal (unstimulated) circulating CgA? To explore this question we studied the effects of selective and nonselective suppression of secretion at several sites within the neuroendocrine system. Selective disruption of sympathetic outflow by trimethaphan decreased basal CgA by 25%, suggesting that sympathetic neurons contribute to circulating CgA. Plasma CgA in patients with unilateral and bilateral adrenalectomy fell within the range observed in normal subjects, weighing against the adrenal medulla as a major source of basal circulating CgA. Selective suppression of a variety of anterior and posterior pituitary cell types decreased plasma levels of the usual resident peptide hormones, but left plasma CgA unperturbed. After propranolol treatment, plasma CgA remained unaltered. Secretin suppressed plasma PTH and calcitonin, but did not alter plasma CgA levels. On the other hand, widespread nonselective suppression of a variety of neuroendocrine secretory cells by somatostatin decreased plasma CgA by 48%. Plasma catecholamines were unaltered by somatostatin infusion, suggesting that somatostatin inhibited CgA release from nonsympathoadrenal sources. During the infusion of somatostatin, the plasma epinephrine increment in response to insulin-induced hypoglycemia was maintained, and plasma CgA did not fall, nor did it rise after somatostatin cessation. Taken together, these findings suggest that somatostatin did not inhibit transport of stimulation-released CgA from the adrenal medulla to the circulation. In conclusion, although the adrenal medulla is the major tissue source of CgA immunoreactivity in man, other neuroendocrine sites, including sympathetic axons and multiple endocrine glands, appear to influence the basal circulating concentration of CgA.
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PMID:Suppression of chromogranin-A release from neuroendocrine sources in man: pharmacological studies. 167 83

PTH and calcitonin are the two major hormones controlling calcium metabolism. Recently two new substances related to these hormones have been isolated: calcitonin gene related peptide (CGRP) and PTH-related protein (PTHrP). CGRP is a potent vasodilator and stimulant of intestinal secretion while PTHrP is probably the agent responsible for humoral hypercalcaemia of malignancy. We report here a patient with a prostatic tumour presenting with vasodilation, diarrhoea and hypercalcaemia. Our investigations revealed that the primary prostatic and liver secondary tumour contained CGRP, calcitonin and PTHrP. Most of the immunoreactive CGRP in the tumour and plasma co-eluted with the biologically active form of CGRP. The circulating levels of CGRP correlated with the presence of the diarrhoea. PTHrP concentration in the tumours was one of the highest reported for any tumour although previous studies may have utilized less than optimal extraction procedures. The somatostatin analogue, octreotide (SMS 201-995), did not reduce the plasma CGRP or the diarrhoea, a finding similar to that seen in patients with medullary thyroid carcinoma and high plasma CGRP. The hypercalcaemia was also unaffected by octreotide administration. This is the first report of a prostatic tumour associated with over-production of calcitonin, PTHrP and CGRP. The major life-threatening effects of this unusual case of prostatic carcinoma were diarrhoea and hypercalcaemia. Both these effects could be tentatively ascribed to newly discovered substances, CGRP and PTHrP. With the greater availability of assays to measure CGRP and PTHrP in plasma, a detailed examination of the incidence of over-production of these substances in various cancers will be possible.
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PMID:Production of calcitonin gene related peptide, calcitonin and PTH-related protein by a prostatic adenocarcinoma. 206 Jan 48

We measured multiple components of serum or plasma in 221 members of a kindred with familial multiple endocrine neoplasia type 1 (FMEN1). The kindred showed typical features of FMEN1; the FMEN1 gene could be traced through 7 generations with 74 members identifiable as gene carriers. Between family screening in 1981 and completion of our study in 1985, we identified 16 previously unscreened members as carriers of the FMEN1 gene. The earliest age at diagnosis of FMEN1 was 17. The tests with the greatest yield of abnormal results among carriers of the FMEN1 gene were albumin-adjusted calcium, PTH, gastrin, and (in females) prolactin. The following tests provided little or no use in identifying carriers: prolactin (in males), pancreatic polypeptide, glucagon, glicentin, insulin, growth hormone, motilin, and somatostatin. Primary hyperparathyroidism was the commonest expression of the FMEN1 gene; the gene penetrance for this trait increased from near 0% before age 15 to near 100% after age 40. It appeared prior to development of serious morbidity from hypergastrinemia or hyperprolactinemia. All 42 co-operating members who were alive and expressing the FMEN1 gene in 1984 showed active or treated primary hyperparathyroidism. Primary hypergastrinemia had a prevalence below half of that for primary hyperparathyroidism at all ages and was not diagnosed in the absence of primary hyperparathyroidism. Primary hyperprolactinemia was still less prevalent than primary hypergastrinemia. It was limited almost exclusively to females.
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PMID:Multiple endocrine neoplasia type I: assessment of laboratory tests to screen for the gene in a large kindred. 287 98

We studied the role of low plasma somatostatin (SRIF) levels in intestinal calcium absorption (CaA) in man. Plasma somatostatin-like immunoreactivity (SLI; pg X ml-1) rose after a 600-cal test meal (from 22.9 +/- 2 basally to 30.6 +/- 3.6 at 45 min, p less than 0.05), but was not affected by an oral Ca load (264 mg). Under intravenous SRIF (0.15 microgram kg-1 h-1) plasma SLI rose from 3.3 +/- 0.4 basally to 24.5 +/- 3 at 45 min (p less than 0.001). CaA was not influenced under these conditions, whereas insulin levels fell significantly and the levels of PTH, calcitonin, glucagon and GH were not changed. A regulating role of SRIF in CaA seems therefore unlikely for human physiology, since neither SLI is influenced by an oral Ca load, nor is CaA changed under postprandial SLI. The fall in insulin under postprandial-like SLI levels favors the view of a hormonal role of SRIF in man.
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PMID:Low-dose infusion of somatostatin in man--no effect upon intestinal calcium absorption but a fall in blood insulin. 287 94

In exceptional cases, acromegaly develops as the clinical expression of an ectopic secretion of Growth Hormone (GH) or Growth Hormone-Releasing Factor (GRF), tumorous in origin. In the present report, we describe an instance of acromegaly caused by the secretion of GRF from a voluminous pancreatic tumor. The resection of this tumor resulted in a temporary disappearance of the biological and clinical symptoms of acromegaly, which then reappeared in conjunction with a rise in plasma GRF. From this pancreatic tumor, substances displaying a potent GRF activity were isolated and characterized. Amino acid analyses revealed that they were related to 3 peptides containing respectively 44, 40 and 37 aminoacids. The largest (hp GRF (1-44)-NH2) referred as hp GRF or somatocrinin is considered to be the primary molecule. The pancreatic tumor was multisecreting as proved by high plasma levels of somatostatin, pancreatic polypeptide and glucagon, normalized after the tumor removal, taken together with the immunocytochemical demonstration of the presence of these peptides in the tissue and with the isolation of somatostatin. In contrast hypercalcemia associated with an elevated plasma level of IR-PTH was unmodified by tumor removal. Diagnosis of acromegaly as ectopic endocrine syndrome will probably be facilitated by plasma GRF radioimmunoassay, as a result of production of anti synthetic GRF antibodies.
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PMID:[Acromegaly, clinical expression of the production of growth hormone releasing factor in pancreatic tumors]. 643 Feb 7

The effects of glucagon and PTH on renal tubular electrolyte handling were studied in anesthetized, thyroparathyroidectomized Brattleboro rats infused with somatostatin. Fractional excretion of Ca and Mg was significantly lower during infusion of both hormones. Micropunctures of same nephrons localized the bulk of the increase in reabsorption in Henle's loop, where both hormones significantly enhanced the reabsorptive capacities for Ca, Mg, and K. Beyond the early distal tubule, Ca and Mg reabsorption was significantly greater during glucagon infusion and Ca reabsorption was significantly greater during PTH infusion. Cyclic adenosine monophosphate at a plasma concentration of 10(-6) M did not reproduce the effects of either glucagon or PTH. These results are similar to the findings reported for the effects of ADH and calcitonin on Ca, Mg, and K tubular handling, but different as far as Na and Cl are concerned, since their loop reabsorption was not significantly altered by glucagon and PTH. The data obtained here for glucagon and PTH, together with those for ADH and calcitonin, support the hypothesis that these four hormones exert similar effects in the thick ascending limb.
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PMID:PTH-like glucagon stimulation of Ca and Mg reabsorption in Henle's loop of the rat. 669 22

PTH-related peptide (PTHrP), which shares 8 of 13 NH2-terminal residues with PTH, causes similar biological effects and interacts with the same receptor as PTH. In the gastrointestinal tract, human PTH and PTHrP-(1-34) relax rat fundic strips. However, the level of their action and the receptor involved in this effect are unknown. The aims of this study were 1) to determine the effects of human PTH-(1-34), human PTHrP-(1-34), -(1-16), and -(7-34) and vasoactive intestinal peptide (VIP) on circular isolated smooth muscle cells from guinea pig ileum; 2) to study the intracellular pathways involved in these effects; and 3) and to characterize the receptors involved by using specific antagonists. Smooth muscle cells were dispersed by enzymatic digestion. Contraction was assessed by measuring the length of 50 cells and expressed as the percent decrease in cell length from the control value. The relaxing effects of PTH, PTHrP and analogs, VIP, or antagonists were expressed as a percentage of the maximal effect observed in their absence. VIP, PTH-(1-34), and PTHrP-(1-34), -(1-16), and -(7-34) had no effect by themselves on these cells. However, when cells were contracted by the sulfated C-terminal octapeptide of cholecystokinin (10 nM), VIP, PTH-(1-34), and PTHrP(1-34) inhibited the sulfated C-terminal octapeptide of cholecystokinin-induced contraction in a concentration-dependent manner, whereas PTHrP-(1-16) and -(7-34) had no effect. The EC50 values of VIP, PTH-(1-34), and PTH-(1-34), and PTHrP-(1-34) were 7 nM, 20 pM, and 20 pM, respectively. The VIP antagonist ([D-P-Cl-Phe6,Leu17]VIP) inhibited VIP-, PTH-(1-34)-, and PTHrP(1-34)-induced relaxation, with IC50 values of 20, 500, and 400 pM, respectively. Likewise, the PTH/PTHrP antagonist [Tyr34-bovine PTH-(7-34)NH2] inhibited PTH-(1-34)-, PTHrP(1-34)-, and VIP-induced relaxation, with IC50 values of 1, 1, and 90 pM, respectively. Preincubation of cells with somatostatin, N-ethylmaleimide, and (R)-p-cyclic adenosine-3',5'-monophosphothioate inhibited the PTH-(1-34), PTHrP(1-34)-, and VIP-induced relaxation. In conclusion, human PTH and PTHrP induce a relaxation of intestinal smooth muscle by a direct myogenic effect. This effect requires the 1-34 amino acid sequence and is mediated by the activation of adenylate cyclase and protein kinase-A. Interactions among PTH, PTHrP, and VIP indicate that they may cross-react with their respective receptors.
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PMID:Parathyroid hormone (PTH) and PTH-related peptide induce relaxation of smooth muscle cells from guinea pig ileum: interaction with vasoactive intestinal peptide receptors. 752 62

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


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