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)

We report the histological, ultrastructural, and immunocytochemical features of six hypothalamic gangliocytomas associated with pituitary GH cell adenomas and/or acromegaly. In four patients, the gangliocytoma was intrasellar, and no hypothalamic investigation was performed; in two patients, autopsy confirmed hypothalamic involvement. Four patients had a gangliocytoma associated with pituitary GH cell adenoma and acromegaly; electron microscopy demonstrated an intimate association between neurons and adenomatous GH cells. One patient had a gangliocytoma and a GH cell adenoma but no clinical evidence of acromegaly. In the sixth patient, clinical and biochemical acromegaly was manifest, but no pituitary adenoma was demonstrated. Using immunocytochemistry, human pancreatic tumor GRF (hptGRF-40) was localized in the majority of neurons of all six gangliocytomas. The pituitary adenomas and nontumorous adenohypophyses were negative for hptGRF-40. In addition, somatostatin, glucagon, and GnRH were demonstrated within some neurons of several tumors; insulin and gastrin stains were equivocal. These findings confirm previous proposals of production of a GRF by such gangliocytomas. While the significance of other peptides found in some of the tumors is uncertain, the presence of hptGRF-40 in neurons of these gangliocytomas supports the theory that GRF excess is the mechanism responsible for over-production of GH and provides evidence for a syndrome of hypothalamic acromegaly.
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PMID:A case for hypothalamic acromegaly: a clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor. 642 59

Somatotropes first appear in the fetal rat pituitary just before term. These cells have never been detected in cultured fetal pituitaries. A modified culture medium has, however, enabled their differentiation in vitro. Hypophysial primordia were explanted on days 13-18 of gestation and cultured in different media until the equivalent of term. Immunoreactive somatotropes could be detected, by light and electron microscopy, in cultured primordia explanted on day 14 of gestation or later. The size and numbers of immunoreactive cells depended on culture medium composition. The control medium, containing insulin, cortisol, T3, and glucagon, proved favorable to somatotrope differentiation and proliferation. Increased insulin concentration reduced somatotrope numbers. In the presence of only insulin and cortisol (or corticosterone) somatotropes were more numerous than in the control. Culture medium enriched with insulin alone, with insulin and T3, or with insulin and glucagon, was not suitable for development of this cell type. Addition of GH-releasing factor ( GHRF ) to the medium during the first culture day did not accelerate the first appearance of the somatotropes but did significantly increase their size. GHRF addition 1/2 h before the end of culture did not modify their morphology. The ultrastructure of somatotropes in vitro is very similar to that observed in vivo on day 21 of gestation. The cells were characterized by their lamellar endoplasmic reticulum and immunoreactive secretory granules (300-400 nm maximal section diameter). Fetal somatotropes can, therefore, be successfully caused to differentiate in vitro. Their appearance depends on insulin and glucocorticoid concentration. T3 and/or glucagon may be inhibitory. GHRF may increase storage in somatotropes. These factors may also regulate the development of somatotropes in vivo.
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PMID:Fetal rat somatotropes in vitro: effects of insulin, cortisol, and growth hormone-releasing factor on their differentiation: a light and electron microscopic study. 642 37

Synthetic human pancreatic GRF (hpGRF-44) was administered as an iv bolus to 139 normal children of short stature and 63 patients with GH deficiency. After a dose of 1 and 2 micrograms hpGRF-44/kg BW, mean plasma GH levels peaked at 15 and 30 min, respectively, with corresponding values of 32.2 +/- 3.6 and 31.8 +/- 2.4 (+/- SE) ng/ml in normal but short children. There were no differences according to sex or age in plasma GH response to hpGRF-44 between the ages of 4 and 18 years. A similar plasma GH response was observed when 2 micrograms hpGRF-44/kg BW was administered two hours after lunch. The overall plasma GH response was greater than that of insulin-induced hypoglycemia and was similar to that obtained in the glucagon-propranolol test. Thirty-five of 63 patients with GH deficiency did not respond to a 2 micrograms hpGRF-44/kg BW. However, plasma GH increases to greater than 5 ng/ml occurred in the remaining 28 patients. Their mean GH level reached a peak at 90 min with a value of 8.8 +/- 0.8 ng/ml. These results suggest that hpGRF-44 is useful for evaluating pituitary GH reserve in children of short stature and that some patients with GH deficiency, diagnosed on the basis of established tests, have GH responses to hpGRF-44.
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PMID:Plasma GH response to hpGRF-44 in normal children of short stature and patients with GH deficiency. 642 64

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

This report describes the histologic, immunocytochemical, and ultrastructural study of a multihormonal carcinoid tumor of the pancreas, secreting a growth hormone releasing factor (GRF) which provoked acromegaly. The patient presented a nonfamilial multiple endocrine neoplasia, type 1. The absence of radiologic signs of a pituitary adenoma in conjunction with elevated plasma levels of pancreatic polypeptide, glucagon, somatostatin, as well as growth hormone (GH), led to the discovery of the tumor. Its surgical excision produced a rapid disappearance of most of the clinical and biologic disorders. No immunoreactive GH was found in the tumor using radioimmunoassay and immunocytochemistry. In contrast, three peptides with GH-releasing activity were extracted and characterized. Immunocytochemistry showed that the GRF-reactive cells, together with rare somatostatin-storing cells, made up areas which demonstrated a medullary pattern of growth with extracellular amyloid deposits. Under electron microscopic examination, actively secreting cells were observed which carried endocrine granules of 100 to 150 nm in diameter. The other regions of the tumor presented a different type of growth and were composed of pancreatic polypeptide-, glucagon-, or somatostatin-reacting cells. Cells immunostained with antisera raised against beta-endorphin were also noted. These data suggest that GRF may be a new biologic marker for pancreatic endocrine tumors.
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PMID:Multihormonal carcinoid tumor of the pancreas. Secreting growth hormone-releasing factor as a cause of acromegaly. 643 52

We have studied the vasorelaxant properties of vasoactive intestinal peptide (VIP) using helical strips of bovine, porcine and human brain arteries in vitro. The resting tension of the arterial strips was increased during experiments by prostaglandin F2 alpha or KCl so as to increase the magnitude of the relaxant response to VIP. Arteries supplying different regions of the bovine brain responded potently to VIP with ED50 values of 1.8 nM, 2.3 nM, 6.8 nM and 9.0 nM for the middle, anterior and posterior cerebral arteries and the basilar artery, respectively. The porcine basilar artery and branches of the human middle cerebral artery responded to VIP with ED50 values of 4.2 nM and 1.6 nM, respectively. The homologous neuropeptide, PHI, relaxed the bovine middle cerebral and porcine basilar arteries less potently than did VIP, with ED50 values for PHI being 11 nM and 43 nM, respectively. However, PHI elicited in the two arteries a maximal vasodilatory response of similar magnitude as did VIP. The other homologous peptides, human pancreatic growth hormone releasing factor 1-40 [hpGRF 1-40], secretin, and glucagon, and the VIP fragments, VIP 1-12 and VIP 10-28, were completely inactive. In contrast, VIP, which had been oxidized to VIP-(Met17 sulfoxide) or VIP-(Met17 sulfone), retained full activity. These structure-activity relationships for relaxation of brain arteries are consistent with previous studies of other biological responses to VIP.
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PMID:Characterization of the relaxant effects of vasoactive intestinal peptide (VIP) and PHI on isolated brain arteries. 654 49

His-DTrp-Ala-Trp-DPhe-LysNH2, [His1,Lys6] GHRP, is a new synthetic hexapeptide which specifically elicits a dosage-related release of GH in vitro and in vivo without a concomitant release of LH, FSH, TSH, or PRL and, in limited in vivo studies, insulin or glucagon. Our results indicate that this small peptide has the attributes of a hypophysiotropic hormone. In vitro the minimum and maximum active dosages ranged from 1-10 ng/ml in the pituitary incubate assay. It was active in rats, monkeys, lambs, calves, and under special experimental conditions chicks, indicating its lack of species dependency. It was active when administered iv, sc, or ip to rats. After iv injection, GH levels rose within 2 min, peaked at +10-20 min, and by 2 h usually had returned to normal. It was not possible to directly compare the potencies of [His1,Lys6]GHRP, and the GH-releasing factors GHRF-44 and GHRF-40 after a single sc injection in rats because the time course of the GH response of these peptides was different. The GH response of [His1,Lys6]GHRP was longer in duration than either of these larger peptides. Both SRIF-14 and SRIF-28 inhibited the GH response of the hexapeptide; however, SRIF-28 was about four times more active than SRIF-14 in vitro and 7.5 times more active in vivo. When this small peptide was administered sc once or twice daily to immature rats for 9 or 25 days, the BW gain increased above the control. At the end of the weight gain studies the pituitary remained fully responsive to the peptide. Thus, [His1,Lys6] GHRP may be a valuable peptide for investigating the function of the pituitary somatotrophs and, in addition, it has the potential for increasing BW gain of a variety of normal animals by inducing GH release via a direct pituitary site of action.
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PMID:On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. 671 55

The dynamics of potassium excretion were examined in normal dogs and dogs with chronic renal insufficiency of at least 4 weeks' duration (remnant model). All animals, in balance on diets providing 15, 50, or 100 mEq of potassium and 100 mEq of sodium, were challenged with 50 mEq of potassium chloride. Immediately thereafter, hourly clearances were obtained for 5 hours. Irrespective of dietary potassium, mean fasting serum potassium and urinary potassium excretion (UKV) were similar in normal and remnant dogs with mean GFR's of 57 +/- 3 and 16 +/- 3 ml/min, respectively. After orogastric administration of 50 mEq potassium, serum potassium rose significantly more in remnant (2.2 to 2.5 mEq/liter) than in normal (0.9 to 1.2 mEq/liter) groups (P less than 0.001). Conversely, UKV increased significantly less, 70 to 96 vs. 151 to 194 micro Eq/min, respectively (P less than 0.001). In 5 hours, normal animals excreted 61 to 67% of the load, but remnant dogs only 30 to 37% (P less than 0.001). In all groups, UKV correlated directly with serum potassium concentration. But this relationship was markedly attenuated in the remnant groups (P less than 0.001) and independent of dietary potassium. In contrast, the same slope describes the relationship between UKV/GRF and serum potassium for all, normal and remnant, animals. The blunted kaliuresis occurred despite the more severe hyperkalemia in remnant than in normal dogs; it was not associated with significant changes in acid-base, diuresis, natriuresis, serum glucose, insulin, and glucagon concentrations and occurred despite prolonged hyperaldosteronism. The results demonstrate a severe limitation of the remnant kidney's ability to rapidly excrete a potassium load. Changes in serum potassium, or a consequence thereof, are important for the urinary excretion of potassium following its acute administration.
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PMID:Renal handling of potassium in dogs with chronic renal insufficiency. 731 8

Proteins with seven transmembrane segments (7TM) define a superfamily of receptors (7TM receptors) sharing the same topology: an extracellular N-terminus, three extramembranous loops on either side of the plasma membrane, and a cytoplasmic C-terminal tail. Upon ligand binding, cytoplasmic portions of the activated receptor interact with heterotrimeric G-coupled proteins to induce various second messengers. A small group, recently recognized on the basis of homologous primary amino acid sequences, comprises receptors to hormones of the secretin/vasoactive intestinal peptide/glucagon family, parathyroid hormone and parathyroid hormone-related peptides, growth hormone-releasing factor, corticotropin-releasing factor, and calcitonin. A cDNA, extracted from a neuroectodermal cDNA library, was predicted to encode a new 886-amino-acid protein with three distinct domains. The C-terminal third contains the seven hydrophobic segments and characteristic residues that allow the protein to be readily aligned with the various hormone receptors in the family. Six egf-like modules, at the N-terminus of the predicted mature protein, are separated from the transmembrane segments by a serine/threonine-rich domain, a feature reminiscent of mucin-like, single-span, integral membrane glycoproteins with adhesive properties. Because of its unique characteristics, this putative egf module-containing, mucin-like hormone receptor has been named EMR1. Southern analysis of a panel of somatic cell hybrids and fluorescence in situ hybridization have assigned the EMR1 gene to human chromosome 19p13.3.
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PMID:EMR1, an unusual member in the family of hormone receptors with seven transmembrane segments. 760 60

Two types of cDNA encoding PACAP receptors were isolated from the rat brain cDNA library by homology screening with a cDNA probe for VIP receptor. Nucleotide sequence analysis indicated that these two types of receptor mRNA were generated by alternative splicing mechanisms. These two cloned cDNAs were introduced into CHO cells respectively. Resultant transformants showed specific binding to [125I]PACAP27 which was displaced by unlabeled PACAP27 but not by VIP. Thus, these receptors are two subtypes of Type I PACAP receptor (Type I-A and Type I-B). The amino acid sequences of rat PACAP receptors deduced by the cDNAs showed a remarkable similarity with rat receptors for VIP, secretin, glucagon, and GHRH. A 6.5 kb significant hybridizing signal of the PACAP receptor mRNA was detected in the rat brain, and slight signal was also detected in the lung and the liver.
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PMID:Molecular cloning and functional expression of rat cDNAs encoding the receptor for pituitary adenylate cyclase activating polypeptide (PACAP). 768 25


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