Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used in situ hybridization histochemistry to examine the postnatal development of the somatostatin (SRIF) synthesizing system in the cerebellum of rats. There are numerous hybridizing neurons from 1 to 9 days after birth. These occur throughout the cerebellum including the developing medulla and cortex except in the external granular cell layer. The lateral cerebellar nucleus also contains SRIF gene-containing cells. The intensity of the signals for SRIF mRNA in the cerebellum decreases with age. There is a drastic decrease in SRIF mRNA in the lateral cerebellar nucleus. SRIF cells cannot be detected in the lateral cerebellar nucleus of adult rats, whereas a small, yet significant number of SRIF cells are scattered in the cerebellar medulla. However, the cerebellum of adult rats still contains a significant number of labeled cells in the granular cell layer, although the intensity for SRIF mRNA decreases from 14 days after birth to adulthood. SRIF gene-expressing cells in the cerebellar cortex are located primarily in the granular cell layer and appear to correspond to Golgi cells judging from their characteristic features. These results are consistent with our previous immunohistochemical study on the decrease of SRIF immunoreactivity in the cerebellum of adult rats. These findings, together with a recent study of transient SRIF receptor-expressing cells in the developing cerebellum suggest that SRIF acts during cerebellar development.
Brain Res Mol Brain Res 1989 Dec
PMID:In situ hybridization analysis of the somatostatin-containing neuron system in developing cerebellum of rats. 257 3

Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is subject to regulation by the cAMP as well as the calcium and cGMP second messenger systems. Treatment of intact rat PC12 cells with neuropeptides including secretin and vasoactive intestinal polypeptide (VIP) stimulated tyrosine hydroxylase activity 2 to 3-fold in vitro. Secretin (EC50 = 10 nM) was about 3 orders of magnitude more potent than VIP (EC50 = 3 microM). A combination of several protease inhibitors failed to enhance the potency of either peptide. Other members of the secretin family including glucagon and peptide histidine isoleucine (PHI) stimulated tyrosine hydroxylase activity to a lesser extent. Somatostatin, which is not homologous to secretin, was ineffective. The maximal response of tyrosine hydroxylase activation to 1 microM secretin occurred within 6-15 sec. Secretin, VIP, and forskolin also enhanced tyrosine hydroxylase activity (3,4-dihydroxyphenylalanine production) in intact cells, as determined by high performance liquid chromatography and electrochemical detection. Secretin, VIP, PHI, and glucagon increased the levels of cAMP in PC12 cells more than 10-fold, as determined by radioimmunoassay. We also demonstrated that cAMP is released from the cells into the incubation medium following secretin treatment. Secretin and VIP treatment also enhanced the activity of cAMP-dependent protein kinase in a concentration-dependent fashion, as measured subsequently in vitro. Based on the greater potency of secretin in comparison with VIP, PHI, and glucagon, we suggest that the PC12 cells contain a secretin-preferring receptor that increases cAMP levels and brings about an activation of tyrosine hydroxylase activity through the stimulation of cAMP-dependent protein kinase.
Mol Pharmacol 1989 Dec
PMID:Regulation of tyrosine hydroxylase activity in rat PC12 cells by neuropeptides of the secretin family. 257 21

Somatostatin (SRIF) is a 14-amino acid peptide hormone that is synthesized as part of a larger precursor, prepro-SRIF, consisting of a signal peptide and a proregion of 80-90 amino acids; mature SRIF is located at the carboxyl-terminus of the precursor. We have used a recombinant retroviral expression vector encoding anglerfish prepor-SRIF-I to infect rat pituitary GH3 cells. The aim of these studies was to investigate the intracellular storage and secretion of the total pool of endogenous GH compared to that of SRIF. Several clonal lines of GH3 cells expressing high or low levels of SRIF were treated with TRH, forskolin, or depolarizing concentrations of potassium, and the levels of intracellular and secreted GH or SRIF were determined using highly sensitive RIAs. Approximately 65% of the total GH was secreted basally, whereas less than 20% of the SRIF-immunoreactive material was basally secreted. Forskolin treatment or potassium depolarization stimulated GH release, but only about 50% above basal levels. In contrast, SRIF secretion was stimulated approximately 5-fold in response to these secretagogues. Based on its lower basal rate of secretion compared to GH and its enhanced release in response to a variety of secretagogues, we conclude that the heterologously expressed SRIF is preferentially targeted to the regulated pathway in GH3 cells.
Mol Endocrinol 1989 Oct
PMID:Retrovirus-mediated expression of preprosomatostatin in rat pituitary GH3 cells: targeting of somatostatin to the regulated secretory pathway. 257 12

Pancreatic D-cell disorder was analyzed in Coxsackievirus B4-induced diabetic mice employing molecular hybridization with a radiolabelled probe to quantitate somatostatin mRNA, and specific immunoprecipitation to measure somatostatin synthesis and its release. Many infected mice showed blood glucose lower than noninfected control animals at 72 h postinfection and 85% became hyperglycemic at 6-8 weeks postinfection. Pancreatic somatostatin decreased by 24% and 43% at 72 h and 6 weeks postinfection, respectively, while somatostatin release in islets from the infected mice increased by 2-fold or more. Residual islet somatostatin content after release was initially higher than control at 72 h and then declined at 6 weeks. Islet cellular RNA content decreased by 35% at 6 weeks, somatostatin mRNA content decreased by approximately 45% at 72 h and 6 weeks postinfection. D-cell disorder - somatostatin mRNA supply, synthesis, and release - is clearly evident in this model, which could be of significance in type I diabetes.
Mol Cell Endocrinol 1989 Nov
PMID:Pancreatic D-cell disorder in coxsackievirus B4-induced diabetic mice. 257 48

The topographical distribution and incidence of endocrine cells in the crypt and villus epithelium and along the length of the mouse intestine was studied. Cells containing somatostatin and bombesin like reactivity were stained by immunocytochemical techniques using polyclonal antiserum. Most of the somatostatin cells were found in the duodenum, jejunum and ileum, and these cells were generally more frequent on the villus compared to the crypts. This may indicate that the somatostatin cells develop late in the endocrine cell lineage. Bombesin like cells were rare in occurrence, and were only present in measureable numbers in the ileum, where they were observed in the crypt and villi. The application of ELISA assays to determine the specificity of the antisera for these peptides is also discussed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:The distribution of endocrine cells along the mouse small intestine. Bombesin and somatostatin producing cells. 257 21

Our laboratory reported previously that chimeric genes encoding either rat somatostatin (SS) or human GH (hGH), but containing the identical mouse metallothionein-I (MT) promoter/enhancer sequences and hGH 3'-flanking sequences, were selectively expressed in the gonadotrophs of transgenic mice. The experiments reported here were designed to identify the DNA sequences responsible for this unexpected cell-specific expression within the anterior pituitary. We produced new transgenic mice expressing fusion genes that tested separately the requirement of the MT or 3'-hGH sequences for gonadotroph expression. A fusion gene that retained the original MT and SS sequences, with a simian virus 40 polyadenylation signal exchanged for the 3'-hGH sequences, no longer directed strong pituitary expression, but was active in the liver. In contrast, a cytomegalovirus promoter/enhancer-SS-hGH fusion gene was expressed at the same high level in the anterior pituitaries of transgenic mice as the originally studied MT-SS-hGH gene. Immunohistochemical analysis indicated that pituitary expression of the cytomegalovirus promoter/enhancer-SS-hGH fusion gene was also restricted to gonadotroph cells in adult mice. These studies indicate that sequences within the 3'-flanking region of the hGH gene can direct expression of chimeric genes to pituitary cells that do not normally produce growth hormone.
Mol Endocrinol 1989 Dec
PMID:Cryptic human growth hormone gene sequences direct gonadotroph-specific expression in transgenic mice. 257 62

A new strain, named WRT cells, has been generated from primary cultures of rat thyroids. The primary culture was grown in Coon's modified Ham's F12 medium with 5% calf serum, insulin, hydrocortisone, transferrin, somatostatin, glycyl-L-histidyl-L-lysine and thyrotropin (TSH). On the basis of the following facts, the WRT cell strain, cloned from the primary culture, was considered 'normal': the cells are euploid, not carcinogenic, not able to grow in soft agar, and show contact inhibition. Their differentiated functions consist of the ability to synthesize thyroglobulin and to take up iodide, and they have a TSH-dependent adenylate cyclase system. TSH increases cellular adenosine 3',5'-cyclic monophosphate (cAMP) levels and [3H]thymidine incorporation in WRT cells from a concentration similar to that active on another clonal rat cell line (FRTL-5), even though the cell replication appears to be differently regulated in the two cell strains. In fact, the WRT cell doubling time is 42 h and they are also able to grow in the absence of TSH, though more slowly. In the same conditions, FRTL-5 cells have a population doubling time of 38 h, but they are not able to grow in the absence of TSH. When the effect of the other growth factors of the medium was studied, insulin appears to be a growth stimulus by itself, while it is only a facilitative step for TSH action in FRTL-5 cells. WRT cells, unlike FRTL-5 cells, can grow with a population doubling time of 80 h, when cultured for prolonged periods in a medium with a low serum concentration (0.5%), but containing insulin plus TSH. In conclusion, the WRT cell strain is a new and interesting experimental model for studying growth factors at the level of the thyroid, especially for their mechanism of action on the TSH receptor.
Mol Cell Endocrinol 1987 Nov
PMID:Insulin stimulates cell growth of a new strain of differentiated rat thyroid cells. 282 50

The xenograft line, UCRU-PR-2, has been characterized further. Established from a primary human undifferentiated small cell carcinoma of the prostate, it has been maintained as a stable xenograft line in nude mice and is currently in passage 9. The tumor has maintained the features of small cell undifferentiated carcinoma but shows epithelial as well as neuroendocrine characteristics. In this paper, we describe synthesis and secretion of peptide hormones, ACTH, beta-endorphin and somatostatin in vivo and ACTH and beta-endorphin in vitro by the tumor, UCRU-PR-2. This suggests that the gene for proopiomelanocortin is expressed and that processing of the molecule occurs. This line may yield insights into the histogenesis of the subtypes of prostate cancer, and also aid studies of regulation of ectopic hormone production.
Mol Cell Endocrinol 1988 Feb
PMID:Ectopic hormone production by a prostatic small cell carcinoma xenograft line. 283 15

We developed a method, termed an H-blot, by which the poly(A) tract of any specific mRNA may be detected by RNA filter hybridization after its removal from the body of the mRNA by a RNase H-catalyzed endonucleolytic cleavage in the 3' untranslated region. Using this method, we studied the modulation of the length of the poly(A) tract of rat vasopressin mRNA in vivo during changes in the levels of this mRNA resulting from a physiologic stimulus, osmotic stress. The poly(A) tract of hypothalamic vasopressin mRNA in hydrated rats was, quite remarkably, approximately 250 nucleotides in length, in contrast to that of somatostatin mRNA, which was approximately 30 nucleotides long. Vasopressin mRNA poly(A) tail length increased progressively from approximately 250 to approximately 400 nucleotides with the application of the hyperosmotic stimulus and declined to base line after its removal; somatostatin mRNA poly(A) tail length did not change during osmotic stress. The poly(A) tract length of total hypothalamic mRNA was between 35 and 140 nucleotides and also did not change with osmotic stress. Modulation of poly(A) tract length of specific mRNAs during stimulation of gene expression may provide an additional level of genetic regulation.
Mol Cell Biol 1988 Jun
PMID:The vasopressin mRNA poly(A) tract is unusually long and increases during stimulation of vasopressin gene expression in vivo. 284 76

We reported recently the presence of somatostatin-like immunoreactivity (SLI) in the glomerulus of rat kidney. In the present study, we examined factors affecting SLI release from isolated rat glomeruli using a perifusion system. Perifusate containing a mixture of essential amino acids stimulated SLI release, while other hormonal agents such as parathyroid hormone, vasopressin, angiotensin II, bradykinin, epinephrine, PGE2, known to have direct actions on the glomerulus, had no discernible effect on SLI release. Addition of somatostatin to the perifusate did not affect either basal or angiotensin II-stimulated PGE2 release from isolated glomeruli. Our preliminary results demonstrate the stimulatory effect of mixed amino acids on somatostatin release from isolated glomeruli. Further studies are needed to elucidate the possible physiological significance of the present findings.
Mol Cell Endocrinol 1985 Jul
PMID:Amino acids release somatostatin-like immunoreactivity from isolated rat glomeruli. 286 84


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