Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteins that bind growth hormone (GHBP) have been identified in the blood of many mammalian and avian species, but not in reptilian species. We carried out binding studies with the serum of turtles using chromatographic techniques as well as the dextran-charcoal separation method. As in other species, we found at least two different GHBPs: one with high MW and low affinity and the other with lower MW and higher affinity. The high affinity GHBP was partially purified using gel filtration and affinity chromatography, reaching a degree of purification of 11,000 times (0.17 nmol/g of serum protein in the serum vs 1900 nmol/g protein in the purified material). When the high affinity GHBP was characterized, it was found to have a dissociation constant (Kd: 2.6 +/- 0.7 nM) similar to those described for mouse or rat, but lower than those for chicken, rabbit or man. The binding capacity (Bmax) was 120 +/- 43 fmoles/mg of protein, which can be also expressed as 1.08 +/- 0.38 pmol/ml of serum. A preliminary MW estimation of 50-60 kDa was obtained for turtle higher affinity GHBP. The specificity of this high affinity GHBP is somatogenic, since bovine GH competes as well as human GH for 125I-hGH bound to binding protein, while ovine PRL competes only partially and with low affinity. Unrelated hormones, as insulin and glucagon, can not displace the 125I-hGH bound to turtle GHBP. A very important seasonal variation in turtle GHBP activity was observed: maximum binding was found in November (springtime), followed by a continuous decline over March and May.
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PMID:Identification and initial characterization of serum growth hormone binding protein in the turtle Chrysemys dorbigni. 925 1

MEN-1 is a hereditary autosomal dominant syndrome characterized by the involvement of parathyroid glands, pancreatic islet cells and anterior pituitary gland. Today molecular genetics permit gene carrier analysis to compare the data obtained with the clinical biochemical tests. The twenty living members of the first, second and third generation of a family with MEN-1 were studied to determine the presence of genetic markers in MEN-1 loci 11q13, by linkage analysis and in affected individuals by biochemical tests and clinical examination. Two very informative polymorphic markers immediately flanking the MEN-1 gene on chromosome 11 band q13 were detected: PYGM and D11S987, haplotypes segregated by two members of the second generation, inherited from their father and two of the third generation: the affected one and one presymptomatic. The third generation had the affected member with renal stones and elevated PTH, PRL and glucagon. The presymptomatic carrier of MEN-1 allele showed elevated PTH. Among the members who inherited the normal allele we found one with elevated gastrin, one with elevated glucagon and one with elevated PTH, all asymptomatic. Of one Argentine family studied, molecular diagnosis allowed us to detect one presymptomatic carrier in the members at risk. As suggested by the available literature, accuracy of molecular diagnosis seems to make it the test of choice to exclude those members at risk for MEN-1 inheriting the normal allele.
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PMID:[Molecular diagnosis in an Argentinian family with multiple endocrine neoplasia type-1 (MEN-1)]. 992 73

Although hypopituitarism is a known complication of head injury, it may be underrecognized due to its subtle clinical manifestations. The nonspecific symptoms may be masked by and may contribute to the physical and psychological sequelae of brain trauma. This study examines the prevalence of neuroendocrine abnormalities in patients rehabilitating from traumatic brain injury. Seventy adults (mean age, 31.5 +/- 1.1 yr; range, 18--58; 46 men and 24 women) with traumatic brain injury an average of 49 +/- 8 months before the study (median, 13 months) underwent a series of standard endocrine tests, including serum levels of TSH, free T(4), insulin-like growth factor I, PRL, testosterone (males), and cosyntropin stimulation. Abnormal results of these tests were followed by dynamic tests of gonadotropin, TSH, and GH secretion. Glucagon stimulation testing in 48 subjects revealed GH deficiency (peak, <3 microg/L) in 14.6%. Free T(4) (n = 6; 8.6%), TSH (n = 7; 10%), or both (n = 2; 2.9%) were low in 21.7%, whereas 87% had both TSH and free T(4) below the midnormal level. Basal morning cortisol was below normal in 45.7% of subjects, whereas cosyntropin-stimulated levels were insufficient (peak, <500 nmol/L) in 7.1%. Hypogonadism and hyperprolactinemia were uncommon. In summary, pituitary hormone deficiencies were identified in a substantial proportion of patients with previous brain injury. GH deficiency, found in 15% by glucagon stimulation testing, may compound the physical and psychological complications of traumatic brain injury and interfere with rehabilitation.
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PMID:Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury. 1139 82

SS, a natural cyclic tetradecapeptide, is a potent suppressor of pituitary GH and TSH secretion. At least five distinct SS receptor (SSTR) subtypes have been cloned and termed SSTRs 1-5. Both SSTR2 and SSTR5 regulate human GH and TSH secretion. Recently, a novel enzymatically stable SS analog, PTR-3173 (Somatoprim), with affinity for human SSTR2, SSTR4 and SSTR5, has been identified. This cyclic heptapeptide analog suppressed rat GH in vivo with no effect on insulin and minimal effect on glucagon secretion. Using primary cultures of human fetal pituitaries (20-24-week gestation) and GH-secreting adenomas, we studied the in vitro inhibitory effects of PTR-3173 on human pituitary secretion. PTR-3173 suppressed GH release from both fetal pituitaries (maximal suppression of 54% with 10 nM) and cultures of GH-cell adenomas (35% suppression with 100 nM). Octreotide and PTR-3173 had comparable inhibitory effects on GH secretion from fetal human pituitaries. TSH was mildly suppressed by PTR-3173, whereas ACTH secretion was not affected in fetal pituitary cultures. In cultures of eight GH-secreting adenomas, octreotide was superior to PTR-3173 in suppressing GH from two adenomas, PTR-3173 was more potent in three other tumors, and three adenomas did not respond significantly to either analog. PTR-3173 suppressed PRL in several mixed GH-PRL adenomas. In conclusion, PTR-3173, a novel SS analog with a unique SSTRs binding combination, is a potent in vitro suppressor of human GH. Combining this inhibitory effect with the lack of effect on insulin secretion, it is suggested that PTR-3173 may be clinically useful for the treatment of acromegaly.
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PMID:PTR-3173 (somatoprim), a novel somatostatin analog with affinity for somatostatin receptors 2, 4 and 5 is a potent inhibitor of human GH secretion. 1563 23

Somatostatin (SST) inhibits pancreatic endocrine secretion. It is generally accepted that SSTR2 and SSTR5 mediate the inhibition of glucagon and insulin release, respectively. The present study was performed to test the hypothesis that SSTR2, but not SSTR5, mediates SST-induced inhibition of insulin release in hamster beta-cells. Both hamster clonal beta-cells HIT-T15 and pancreatic islets were used to test this hypothesis. Both SST and a nonpeptide SSTR2 agonist L-779,976 (1-100 nM) inhibited insulin release from HIT-T15 and islets in a concentration-dependent manner. In contrast, nonpeptide agonists for SSTR1, 3, 4 and 5 at the highest concentration studied (1 microM) failed to inhibit insulin release. PRL-2903, a peptide SSTR2 antagonist (0.1-1 muicroM), antagonized SST-induced inhibition of insulin release in a concentration-dependent manner. Taken together, we conclude that, in hamster beta-cells, SST inhibits insulin release via SSTR2 but not SSTR5.
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PMID:Somatostatin inhibits insulin release via SSTR2 in hamster clonal beta-cells and pancreatic islets. 1592 1

Multiple endocrine neoplasm type 1 (MEN1) syndrome predisposes to the development of endocrine and non-endocrine tumors with an autosomal dominant pattern of inheritance. Different mutations have been found throughout the gene with a variable phenotype expression. The proband, a Caucasian man, was admitted to our department in 2001, at the age of 51 because of a 1-yr history of diarrhoea and hypertension. He reported a previous intestinal resection for bowel occlusion with a histological diagnosis of unspecified mesenchymal neoplasia. He had also undergone a left adrenalectomy for a large nonfunctioning adrenal adenoma. Subsequently, he had suffered from gastralgia and melena; a gastroduodenoscopy showed an erosive gastritis. His family history was negative for endocrine disorders. On physical examination, multiple abdominal cutaneous lipomas and facial angiofibromas were observed. Biochemical screening revealed a primary hyperparathyroidism and an increase in circulating levels of PRL, chromogranin-A, gastrin and glucagon. The whole body computed tomography (CT) scan, the 111In-octreotide scan and the pituitary magnetic resonance imaging (MRI) did not reveal any abnormality. The presence of small neuroendocrine tumors was suspected by a positron emission tomography uptake in the epigastric region. The endoscopic ultrasound revealed a pancreatic lesion sized 1.1 cm that is under evaluation. Direct DNA sequencing analysis of the proband MEN1 gene revealed the 579delG frameshift mutation in the exon 3. The genetic screening of the family revealed the same mutation in 3 out of 5 offspring. The biochemical screening revealed some features of the MEN1 syndrome in all three of them. In conclusion, a novel frameshift MEN1 mutation was found in kindred with an apparently negative family history. Our experience confirms that MEN1 syndrome is a complex and underestimated condition, unless specifically investigated by trained specialists.
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PMID:MEN1 family with a novel frameshift mutation. 1679 69


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