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)

We examined the expression of regulated endocrine-specific protein of 18-kD (RESP18) in selected peptidergic and catecholaminergic neurons of adult rat brain. In the hypothalamic paraventricular, supraoptic, and accessory nuclei, RESP18 mRNA was highly expressed in neurons immunostained for oxytocin and vasopressin. RESP18 mRNA was also highly expressed in paraventricular nucleus neurons immunostained for corticotropin-releasing hormone, thyrotropin-releasing hormone, and somatostatin. RESP18 mRNA was expressed in POMC cells of the arcuate nucleus, in neuropeptide Y cells of the dorsal tegmental nucleus, lateral reticular nucleus, and hippocampus, and in brainstem catecholaminergic neurons. RESP18 mRNA expression was high in all paraventricular and arcuate neurons, but RESP18 protein was detectable in the perikarya of a subset of these neurons, suggesting an important post-transcriptional component to the regulation of RESP18 expression. RESP18 antisera immunostained perikarya but not axon fibers or terminals. Sub-cellular fractionation of homogenates of several hypothalamic nuclei identified RESP18 protein in fractions enriched in endoplasmic reticulum. The presence of 22- and 24-kD RESP18 isoforms in the neural lobe of the pituitary indicated that some RESP18 protein exited the endoplasmic reticulum. The post-transcriptional regulation of RESP18 expression and localization of RESP18 protein primarily to the endoplasmic reticulum suggests that RESP18 plays a regulatory role in peptidergic neurons.
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PMID:Expression of RESP18 in peptidergic and catecholaminergic neurons. 928 14

There is growing evidence that protein disulphide isomerase (PDI) has a common chaperone function in the endoplasmic reticulum. To characterise this function, we investigated the interaction of purified PDI with radiolabelled model peptides, somatostatin and mastoparan, by cross-linking. The interaction between the peptides and PDI was specific, for it showed saturation and was abolished by denaturation of PDI. The interaction between a hydrophobic peptide without cysteine residues was much more sensitive to Triton X-100 than the interaction between PDI and a more hydrophilic peptide with or without cysteine residues. We therefore propose that hydrophobic interactions between protein disulphide isomerase and peptides play an important role in the binding process. The interaction between PDI and the bound peptide therefore is enhanced by the formation of mixed disulphide bonds.
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PMID:Interactions between protein disulphide isomerase and peptides. 931 Mar 57

We examined the cellular localization of regulated endocrine-specific protein of 18 kDa (RESP18) and mRNA in peripheral endocrine tissues. In situ hybridization and immunocytochemistry identified RESP18 mRNA in most cells of the anterior and intermediate pituitary, with RESP18 protein apparent in many anterior pituitary cells but very few intermediate pituitary cells. In the adrenal medulla and superior cervical ganglion, RESP18 mRNA co-localized with dopamine beta-mono-oxygenase and neuropeptide Y. In the thyroid, RESP18 mRNA was localized to C-cells. RESP18 mRNA was expressed in most of the cells of the pancreatic islets, co-localizing with insulin, glucagon, and somatostatin. No RESP18 mRNA or protein was detected in the adrenal cortex, ovary, neural lobe of the pituitary, parathyroid, exocrine pancreas, thyroid follicular cells, placenta, mammary tissue, liver, lung, or atria. As in the intermediate lobe of the pituitary, high levels of RESP18 mRNA in the pancreatic islets and adrenal medulla did not always correlate with immunodetectable RESP protein, suggesting that post-transcriptional mechanisms are important in controlling RESP18 expression. Western blot analyses identified 18 kDa RESP and higher molecular weight isoforms of RESP in most tissues and in plasma. Subcellular fractionation of the anterior pituitary identified 18 kDa RESP18 in fractions enriched in endoplasmic reticulum and secretory granules, with the higher molecular weight isoforms of RESP18 concentrated in fractions enriched in secretory granules. The broad neuroendocrine distribution of RESP18 suggests that it subserves an important function in the secretory pathway that is common to the production of many secreted peptides.
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PMID:The expression of regulated endocrine-specific protein of 18 kDa in peptidergic cells of rat peripheral endocrine tissues and in blood. 941 67

Growth hormone (GH) synthesis and release from the pituitary is regulated by hypothalamic releasing hormone, insulin-like growth factor-1 (IGF-1), and somatostatin. However, the potential effects of pharmacological doses of exogenous GH on the pituitary are not well studied. To determine the potential chronic effects of exogenous GH on pituitary morphology in dogs, porcine GH (pGH) was administered subcutaneously to 3 groups of dogs (4 animals/sex/group) at doses of 0.025, 0.1, and 1.0 IU/kg/day for 14 wk. A group (4/sex) of dogs served as the vehicle control. The pituitaries from all dogs were weighed and fixed in appropriate fixatives for light and electron microscopic examination; in addition, cells of the pars distalis were quantitated by a point counting method following immunostaining to identify cells containing GH, prolactin (PRL), and adrenocorticotrophic (ACTH) hormones. Administration of pGH resulted in a statistically significant (p < or = 0.05) increased pituitary weight through the high dose. By light microscopy (LM), hypertrophy of pars distalis cells was evident in mid- and high-dose female dogs. The pituitaries of dogs given the lowest dose (0.025 IU/kg/day) of pGH were not remarkable based on weight and LM findings. In addition, transmission electron microscopic (TEM) examination of the pituitary gland of high-dose demonstrated, in both sexes, pituitary cells with variably dilated rough endoplasmic reticulum and decreased numbers of secretory granules; some of these cells reacted positively to GH immunostaining. Quantitative analysis of the pituitary gland of high-dose males and females showed an increase in the absolute volume of all cell populations studied: GH-, PRL-, and ACTH-positive cells. Based on the LM and TEM findings, the increased volume of the cell populations studied is likely related to cellular hypertrophy. The expected elevation in serum GH levels following repeated administration of pGH and an associated elevation in serum IGF-1 levels resulted in morphologic changes in the pituitary gland of dogs given high doses (> or = 0.1 IU/kg/day) of pGH; these observations differed from the reported findings in pituitaries of transgenic mice secreting large quantities of bovine GH.
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PMID:Morphological changes in the pituitary gland of dogs chronically exposed to exogenous growth hormone. 954 58

An autosomal recessive murine mutation, coined "aly/aly" or "alymphoplasia," was recently reported. Homozygotes for aly are defective in both humoral and cell-mediated immune function and have diffuse lymphoid cell infiltration of various tissues, particularly around the conduit ducts of the pancreas and salivary glands. In pilot studies in our laboratories, aly/aly mice were found to have peculiar biliary tract lesions, which were analyzed histologically and immunohistochemically in the present study. The livers of aly/aly mice older than 8 weeks consistently showed a variable lymphoid cell infiltration with lymph follicle formation in portal tracts; intrahepatic biliary epithelial cells showed various types of damage including pseudopyloric gland metaplasia and proliferative changes. In addition, the extrahepatic bile duct and intrahepatic large bile duct were found to contain an acidophilic substance in their epithelial cytoplasm. In the lumen and occasionally in the cytoplasm of these bile ducts, acidophilic crystals were also seen. Ultrastructurally, the intracytoplasmic acidophilic substances consisted of membrane-bound intracytoplasmic inclusions with homogeneous electron density, likely derived from rough endoplasmic reticulum (ER). Immunohistochemically, the cytoplasmic acidophilic substances were simultaneously positive for cystatin C, gastrin, serotonin, and somatostatin. In contrast, the acidophilic crystals did not react with any of these antibodies. These findings suggest that the intracytoplasmic acidophilic substances may contain a precursor of the peptide hormones, possibly because of defective secretion or intracellular transport. We believe that the aly/aly mouse is a useful model for the analysis of biliary metabolic events, and for studies of the interaction of the immune system and biliary destruction.
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PMID:aly/aly mice: a unique model of biliary disease. 962 Mar 19

The objective of the present study was to further investigate the ionic mechanism of the action of GHRP-6 on male rat pituitary cells in culture. A synthetic hexapeptide, GHRP-6 stimulates the secretion of growth hormone both in vivo and in vitro. It is generally accepted that Ca2+ and protein kinase C but not cAMP are involved in the signal transduction pathway of the action of GHRP-6. Ca2+-influx through voltage-gated Ca2+ channels and mobilization of internal stored Ca2+ are thought to be responsible for an increase in cytosolic Ca2+ concentration. For activation of the voltage-gated Ca2+ channels, however, it is not determined whether the membrane Na+ permeability plays a role. To answer this question, we measured intracellular Na+ concentration of the pituitary cells with ion imaging technique. We found that GHRP-6 increased [Na+]i; the Na+ response depended on the presence of extracellular Na+ and was blocked by Gd3+, known as a blocker of nonselective cation channels but not by tetrodotoxin, a blocker of the voltage-gated Na+ channel; thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ ATPase, had no effect on the response; Ca2+ chelating agent, BAPTA had no inhibitory effect on the response; ouabain, an inhibitor of Na+-K+ ATPase, did not block the rise in [Na+]i induced by GHRP-6; somatostatin, which hyperpolarizes the cells by activating K+ channels, suppressed the response. These data clearly showed that GHRP-6 increased [Na+]i in the rat pituitary cells including somatotrophs. The rise in [Na+]i is likely to be due to an increase in the membrane Na+ permeability which should depolarize the cells, thereby activating the voltage-gated Ca2+ channels. This process leads to an influx of Ca2+ and subsequent increase in [Ca2+]i which results in an exocytotic release of GH.
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PMID:The effect of GHRP-6 on the intracellular Na+ concentration of rat pituitary cells in primary culture. 1052 Jan 28

Growth hormone (GH) modulates the hypothalamic release of somatostatin and GH-releasing hormone; however, there has been no evidence of GH autoregulation on the pituitary somatotroph. To determine the effects of GH on its own regulation, we examined the pituitaries of giant transgenic mice expressing a GH agonist (E117L), dwarf transgenic mice expressing a GH antagonist (G119K), and dwarf mice devoid of the GH receptor/binding protein (GHR/BP). In the E117L transgenic mice, the number and distribution of pituitary GH-immunoreactive cells were unchanged from nontransgenic littermate controls; an ultrastructural examination revealed typical, densely granulated somatotrophs. In contrast, the pituitaries of the G119K mice contained both moderately granulated somatotrophs and a sparsely granulated (SG) population with well-developed synthetic organelles and a distinct juxtanuclear globular GH-staining pattern. GHR/BP-deficient mice exhibited a marked reduction in the intensity of cytoplasmic GH immunoreactivity; however, prominent GH staining in the juxtanuclear Golgi was seen. GH-immunoreactive cells were increased in number, and the reticulin network pattern was distorted; stains for proliferating cell nuclear antigen confirmed mild hyperplasia. Electron microscopy showed that the somatotrophs were hyperactive SG cells with prominent endoplasmic reticulum membranes, large Golgi complexes, and numerous mitochondria. These findings are consistent with synthetic and secretory hyperactivity in pituitary somatotrophs due to the reduced GH feedback regulation. The changes are most striking in animals that are devoid of GHR/BP and less marked in animals expressing a GH antagonist; both models had reduced insulin-like growth factor-I levels, but the more dramatic change in the GHR/BP animals can be explained by abrogated GH signaling. This represents the first evidence of direct GH feedback inhibition on pituitary somatotrophs, which may have implications for the use of GH analogs in different clinical settings.
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PMID:Evidence for growth hormone (GH) autoregulation in pituitary somatotrophs in GH antagonist-transgenic mice and GH receptor-deficient mice. 1070 16

Transgenic rats carrying a PEPCK-SV40 large T-antigen (TAg) transgene rapidly develop numerous pancreatic islet cell neoplasms, the cells of which express TAg. Although many of the larger neoplasms contain relatively undifferentiated cells, many tumors contain areas of well-differentiated cells with abundant endoplasmic reticulum (ER) and secretory granules for endocrine hormones like those observed in normal pancreatic islets. In the well-differentiated lesions, glucagon-producing alpha-cells, insulin-producing beta-cells, and somatostatin-producing delta-cells are readily identifiable morphologically under the electron microscope. Beta-cells were observed in all normal and hyperplastic islets, and nests of these cells were scattered throughout the larger neoplasms. These nests varied from small clusters of epithelium-like cells that stain intensely for insulin, to sheets of small, basophilic cells that stain more diffusely for the hormone. Alpha-cells were also present in all of the normal and hyperplastic islets, but in larger hyperplastic islets, the peripheral localization was absent. Larger neoplasms contained many nests of glucagon-expressing cells, as well as scattered glucagon-producing single cells. Delta-cells were rarely observed in the hyperplastic islets and in the neoplasms. Blood-glucose levels were unaltered in the transgenic animals relative to their nontransgenic litter mates. Thus although these islet cell neoplasms express several polypeptide hormones, there is no obvious clinical effect of such expression in vivo.
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PMID:Multiple polypeptide hormone expression in pancreatic islet cell carcinomas derived from phosphoenolpyruvatecarboxykinase-SV40 T antigen transgenic rats. 1070 38

This study was aimed to localize and characterize the somatostatin-immunoreactive (SOM-IR) neurons in the rat cuneate nucleus (CN). By immuno-histochemistry, the SOM-IR neurons, which were widely distributed in the nucleus, were round, spindle or multiangular in shape (mean area = 226.1 +/ -3.1 microm(2), n = 1016). By electron microscopy, the neurons shared all the ultrastructural features of the cuneothalamic neurons (CTNs) which showed a slightly indented nucleus and a fairly rich cytoplasm containing well-developed Golgi apparatuses and rough endoplasmic reticulum (rER). The SOM immunoreaction product filled the cytoplasm of the neurons extending from the soma to the proximal and distal dendrites, which were postsynaptic to unlabeled boutons. In addition to soma and dendrites, SOM-IR boutons were also identified which made axodendritic synaptic contacts with SOM-IR dendrites. The SOM-IR neurons were characterized by using anti-SOM pre-embedding immunolabeling coupled with horseradish peroxidase (HRP) retrograde method, or SOM immunolabeling along with anti-glutamate, gamma-aminobutyric acid (GABA) or glycine post-embedding immunolabeling for identification of CTNs, glutamate-IR, GABA-IR and glycine-IR neurons, respectively. It was shown that more then 80% of the CTNs contained SOM and, furthermore, they contained glutamate but not GABA or glycine. On the basis of present findings, it is suggested the majority of the SOM-IR neurons in the rat CN are CTNs and that they may be involved in modulation of somatosensory synaptic transmission.
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PMID:Somatostatin-IR neurons are a major subpopulation of the cuneothalamic neurons in the rat cuneate nucleus. 1100 Apr 47

The development of a variety of enteroendocrine cells of the gut is poorly understood. We tested whether immature intestinal stem cells were switched to multiple enteroendocrine hormone-producing cells by in vitro transfer of a homeobox gene. We transfected the pancreatic-duodenal homeobox 1 gene (Pdx1) into IEC-6 cells, an embryonic intestinal epithelial cell line derived from a normal rat, and selected the cells that overexpressed Pdx1 by 150-fold compared with control. The cells were examined for differentiation into enteroendocrine cells by immunocytochemical and electron microscopic analyses. Transfected cells cultured on micropore filters formed a trabecular network piled up on monolayer cells. These trabecular cells showed nuclear localization of Pdx1 protein and contained well-developed rough endoplasmic reticulum as well as many secretory granules of pleomorphic shape in the cytoplasm. Antibodies against chromogranin A, serotonin, cholecystokinin, gastrin, and somatostatin stained these secretory granules in the cytoplasm. Furthermore, immunofluorescence double staining analysis showed that different hormones were produced within a cell. These results provide the evidence that immature intestinal epithelial cells can differentiate into multiple hormone-producing enteroendocrine cells in response to overexpression of Pdx1.
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PMID:Differentiation of immature enterocytes into enteroendocrine cells by Pdx1 overexpression. 1140 76


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