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)

Six insulin-like growth factor binding proteins (IGFBP) have been identified in the conditioned medium from sheep thyroid cells cultured under serum-free conditions. IGFBPs of 32, 28, 23 and 19 kDa were secreted by cells cultured for 14 days in serum-free and hormone-free medium. The constitutive secretion of IGFBP was inhibited by thyrotropin (TSH, 0.3 mU per mL). The effect was most marked on the secretion of the 28 kDa BP. High insulin concentrations stimulated the secretion of this IGFBP. The stimulatory effects of insulin were inhibited by TSH. Growth hormone treatment decreased the secretion of the 28 kDa protein. Tetradecanoylphorbol-13 acetate (TPA) and epidermal growth factor (EGF) both of which stimulate thyroid cell growth but inhibit differentiated function, markedly stimulated IGFBP secretion and induced the appearance of a 46 and a 150 kDa IGFBP. The effects of EGF and TPA were not identical. A rat IGFBP-2 cDNA reacted with sheep thyroid RNA of approximate size 1.6 kb. TPA treatment increased IGFBP-2 mRNA. Other hormones used to enhance differentiation and growth in thyroid cells in culture i.e. transferrin, somatostatin, cortisol and glycyl-histidyl-lysine acetate had no marked effects on IGFBP secretion nor on TSH-dependent, insulin-mediated iodide uptake and organification and cell growth. We show a correlation between secretion of high molecular weight IGFBP with enhanced growth but decreased function. Conversely, we find a correlation between decreased secretion of the 28 kDa BP and increased growth and function.
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PMID:Thyrotropin inhibits while insulin, epidermal growth factor and tetradecanoyl phorbol acetate stimulate insulin-like growth factor binding protein secretion from sheep thyroid cells. 172 84

The ability of TSH to stimulate synthesis and release of thyroid hormones in ovine thyroid follicles in vitro depends partially on a synergy with insulin-like growth factors (IGFs). The cellular availability of IGFs may be influenced by the release of several IGF binding proteins (IGFBPs). The purposes of these studies was to 1) further characterize the species of IGFBPs synthesized by thyroid follicles, 2) examine the ability of TSH and cortisol to alter IGFBP gene expression and protein release, and 3) investigate the actions of exogenous IGFBPs on thyroid cell function. Adult sheep thyroid follicles were isolated after collagenase digestion, grown to confluence in Coon's modified Ham's F12M medium (OH) with the addition of transferrin, glycylhistidyl-lysine, somatostatin (3H), cortisol and insulin, and maintained in serum-free test media with or without further supplements for up to 48 h. Conditioned media were analyzed for IGFBP presence by Western ligand blotting, and by immunoblotting using specific antisera against bovine IGFBP-2 and human IGFBP-5. IGFBP mRNAs from follicles were identified by Northern blot hybridization using [32P]labeled complementary DNAs encoding ovine IGFBP-1 or -2, and rat IGFBP-4, -5, or -6. Uptake and organification of Na[125I] were measured by incorporation into trichloroacetic acid-precipitable material. Isolated thyroid follicles synthesized four species of IGFBPs in either 0H or 3H medium as detected by ligand blotting, of sizes 40-46, 34, 28, and 18 kilodaltons (kDa), respectively. The 32 kDa IGFBP was identified immunologically as IGFBP-2, whereas the 28 kDa and 18 kDa species were identified as IGFBP-5. Northern blot hybridization of total RNA from cells in 3H medium demonstrated an IGFBP-2 messenger RNA (mRNA) [1.4 kilobase (kb)], an IGFBP-4 mRNA (2.6 kb), and two IGFBP-5 mRNAs (6 kb and 1.8 kb). No IGFBP-1 or -6 mRNAs were detected. Incubation of cultured follicles with TSH (30-500 microU/ml) caused a dose-dependent decrease in the abundance of all IGFBP mRNAs and released proteins, which were reduced further by TSH together with cortisol (10 nM). When the inhibitory effect of TSH and cortisol was removed, IGFBP-2 mRNA increased within 3 h and was 7-fold greater within 12 h. IGFBP-2 did not appear in the conditioned medium until 12 h after TSH removal, along with the other IGFBP species.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hormonal regulation and biological actions of insulin-like growth factor binding proteins in isolated ovine thyroid follicles. 750 36

The purpose of this research was to study the chemical reactivity of a somatostatin analogue, octreotide acetate, formulated in microspheres with polymers of varying molecular weight and co-monomer ratio under in vitro testing conditions. Poly(D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide) (PLA) microspheres were prepared by a solvent extraction/evaporation method. The microspheres were characterized for drug load, impurity content, and particle size. Further, the microspheres were subjected to in vitro release testing in acetate buffer (pH 4.0) and phosphate buffered saline (PBS) (pH 7.2). In acetate buffer, 3 microsphere batches composed of low molecular weight PLGA 50:50, PLGA 85:15, and PLA polymers (< or =10 kDa) showed 100% release with minimal impurity formation (<10%). The high molecular weight PLGA 50:50 microspheres (28 kDa) displayed only 70% cumulative release in acetate buffer with significant impurity formation (approximately 24%). In PBS (pH 7.4), on the other hand, only 50% release was observed with the same low molecular weight batches (PLGA 50:50, PLGA 85:15, and PLA) with higher percentages of hydrophobic impurity formation (ie, 40%, 26%, and 10%, respectively). In addition, in PBS, the high molecular weight PLGA 50:50 microspheres showed only 20% drug release with ~66% mean impurity content. The chemically modified peptide impurities inside microspheres were structurally confirmed through Fourier transform-mass spectrometry (FT-MS) and liquid chromatography/mass spectrometry (LC-MS/MS) analyses after extraction procedures. The adduct compounds were identified as covalently modified conjugates of octreotide with lactic and glycolic acid monomers within polymeric microspheres. The data suggest that due to steric hindrance factors, polymers with greater lactide content were less amenable to the formation of adduct impurities compared with PLGA 50:50 copolymers.
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PMID:Identification of chemically modified peptide from poly(D,L-lactide-co-glycolide) microspheres under in vitro release conditions. 1519 45