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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rate of transcription of the hepatic phosphoenolpyruvate carboxykinase (PEPCK) and insulin-like growth factor-binding protein 1 (IGFBP-1) genes is stimulated by glucocorticoids and inhibited by insulin. In both cases, the effect of insulin is dominant, since it suppresses both basal and glucocorticoid-stimulated PEPCK or IGFBP-1 gene transcription. Analyses of both promoters by transfection of PEPCK or IGFBP-1-chloramphenicol acetyltransferase fusion genes into rat hepatoma cells has led to the identification of insulin response sequences (IRSs) in both genes. The core IRS, T(G/A)TTTTG, is the same in both genes, but the PEPCK promoter has a single copy of this element whereas the IGFBP-1 promoter has two copies arranged as an inverted palindrome. The IGFBP-1 IRS and PEPCK IRS both bind the alpha and beta forms of hepatic nuclear factor 3 (HNF-3), although the latter does so with a sixfold-lower relative affinity. Both the PEPCK and the IGFBP-1 IRSs also function as accessory factor binding sites required for the full induction of gene transcription by glucocorticoids. A combination of transient transfection and DNA binding studies suggests that HNF-3 is the accessory factor that supports glucocorticoid-induced gene transcription. In both genes, the HNF-3 binding site overlaps the IRS core motif(s). A model in which insulin is postulated to mediate its negative effect on glucocorticoid-induced PEPCK and IGFBP-1 gene transcription indirectly by inhibiting HNF-3 action is proposed.
Mol Cell Biol 1995 Mar
PMID:Hepatic nuclear factor 3- and hormone-regulated expression of the phosphoenolpyruvate carboxykinase and insulin-like growth factor-binding protein 1 genes. 753 83

We have recently established an immortalized granulosa cell line as a model system to investigate ovarian function, with particular emphasis on the insulin-like growth factor (IGF) regulatory system. Previous results have shown that these cells express mRNAs for IGF-binding proteins (IGFBPs)-2 to -5. These IGFBPs are also detected by ligand blots. The current work evaluated the regulation by the IGFs and cAMP on the IGFBPs and their mRNAs and compared the findings to that in primary culture. Our results indicate that levels of the IGFBPs are controlled, in part, by expression of the mRNAs. However, evidence for post-transcriptional regulation was also discovered. IGFBP-3 was stimulated by IGF-I, IGFBP-4 by forskolin, and IGFBP-5 by IGF-I. IGFBP-2, -3, and -4 are expressed under basal conditions whereas IGFBP-5 is only detectable after IGF-I induction. An alteration in the biphasic actions of cAMP in this cell line, as compared to primary culture, was evident.
Mol Cell Endocrinol 1994 Dec
PMID:IGF-binding proteins are differentially regulated in an ovarian granulosa cell line. 753 34

The effect of a gonadotropin-releasing hormone-agonist (GnRH-a) on the synthesis of insulin-like growth factor-binding protein-5 (IGFBP-5), a physiological marker for atresia, was investigated. Granulosa cells obtained from diethylstilbestrol (DES)-treated immature female rats were cultured in serum-free medium for 72 h with GnRH-a and the conditioned media were subjected to immunoblot analysis using rat IGFBP-5 specific antibody. GnRH-a caused a dose-dependent (ED50 = 8.6 x 10(-11) M) accumulation of IGFBP-5, which migrated as 35 (non-glycosylated) and 36 kDa (glycosylated) bands under reducing conditions. A maximally effective dose of GnRH-a (10(-9) M) caused a 4-fold increase in IGFBP-5 accumulation. In contrast, increasing doses of porcine follicle-stimulating hormone (pFSH) caused a biphasic effect on IGFBP-5 accumulation. A low dose of pFSH (0.25 ng/ml) increased and higher doses of pFSH (22.5 ng/ml) decreased the 35 and 36 kDa IGFBP-5 bands. In the presence of high doses of pFSH (20.75 ng/ml), a 22 kDa band corresponding to a cleaved IGFBP-5 fragment appeared in the media. When the granulosa cells were cultured with a saturating dose of pFSH, co-addition of GnRH-a dose dependently inhibited the FSH effects (ED50 = (2.3-3.7) x 10(-10) M). The GnRH-a effects were completely blocked by co-incubation with GnRH-antagonist. IGFBP-5 mRNA accumulation levels were increased by GnRH-a in a dose dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1995 Apr 28
PMID:Gonadotropin-releasing hormone overcomes follicle-stimulating hormone's inhibition of insulin-like growth factor-5 synthesis and promotion of its degradation in rat granulosa cells. 754 20

Using a solution phase assay we have demonstrated that sheep adipose tissue explants secrete insulin-like growth factor binding proteins (IGFBPs) when cultured in serum-free medium over a 24 h period. Further, we demonstrate that secretion of IGFBP(s) is inhibited (up to 50%) by incubation of the cultures in the presence of 10(-8) M dexamethasone. This inhibitory effect is overcome when insulin (10 ng/ml) and ovine growth hormone (100 ng/ml) are incubated together (but not separately) with glucocorticoid. Further characterisation of this IGF binding activity by high performance size exclusion chromatography and Western ligand blot analysis indicated that under our culture conditions sheep adipose tissue explants secrete one predominant 21 kDa IGFBP and it is this BP which is hormonally regulated as described above. We discuss our results in the context of endocrine/paracrine/autocrine control of adipose tissue metabolism and differentiation.
Mol Cell Biochem 1995 Apr 26
PMID:Glucocorticoids regulate the secretion of a 21kDa-IGF-binding protein by sheep adipose tissue explants. 754 83

Recent studies suggest a role for the insulin-like growth factor (IGF) system in the repair of damaged tissue following hypoxic-ischemic injury in the infant rat brain. We have used a unilateral model of hypoxic-ischemic injury to assess the possible involvement of two IGF binding proteins (IGFBPs), IGFBP-4 and IGFBP-5, in the post-asphyxial response. Ligation of the right carotid artery of 21-day-old rats was followed by either 15 min or 60 min exposure to 8% oxygen to produce moderate and severe damage respectively. Using in situ hybridization, the distribution of IGFBP-4 and IGFBP-5 mRNA was determined in brains collected over 10 days following the insult. In the control brains (no damage), both IGFBPs were expressed in distinct regions. IGFBP-4 mRNA was detected in limited areas of the hippocampus and in several cortical layers, while IGFBP-5 mRNA was found primarily in the thalamus. In response to hypoxic-ischemic injury, IGFBP-4 mRNA expression was reduced in regions of neuronal loss, suggesting a neuronal origin for IGFBP-4. The expression of IGFBP-5 mRNA was not altered by the 15 min insult, but was heavily induced from 3 days following the 60 min insult, particularly in the subependymal layer and adjacent white matter on the ligated hemisphere. This suggests that IGFBP-5 may be involved in recovery from severe hypoxic-ischemic injury and may be important in the regeneration of oligodendrocytes.
Brain Res Mol Brain Res 1993 May
PMID:Differential expression of insulin-like growth factor binding proteins (IGFBP) 4 and 5 mRNA in the rat brain after transient hypoxic-ischemic injury. 768 82

The developmental expression of the individual components of the insulin-like growth factor (IGF) system in pigs was examined. Serum IGF-I and IGF-binding protein-3 (IGFBP-3) levels were low during fetal life and increased during postnatal development. Levels of mRNAs encoding these proteins were not greater for liver than for nonhepatic tissues (skeletal muscle, lung, kidney) and did not increase during the postnatal period, whereas hepatic growth hormone (GH) receptor mRNA expression was increased postnatally. Serum IGF-II levels exceeded IGF-I levels at all developmental stages examined and both exhibited postnatal increases. IGF-II mRNA abundance, in contrast, was high in the fetal tissues with the exception of lung and declined during the perinatal transition. Hepatic IGFBP-2 mRNA and serum IGFBP-2 levels increased during the latter half of gestation and then declined postnatally. The levels in muscle and liver of type I IGF receptors and the corresponding mRNAs also exhibited postnatal decreases. The discordance of changes in hepatic IGF-I and IGF-II mRNA abundance with serum IGF levels during the postnatal period does not support the concept that liver is the primary endocrine source of IGFs in the young pig. The postnatal increases in serum IGF levels may reflect decreased plasma clearance rates of these peptides which may be related to the transition in IGFBP type from IGFBP-2 to IGFBP-3 in blood and the reduced tissue expression of IGF receptors.
Mol Cell Endocrinol 1993 May
PMID:Ontogeny of the porcine insulin-like growth factor system. 768 18

The insulin-like growth factor (IGF) binding proteins (IGFBPs) have several functions, including transporting the IGFs in the circulation, mediating IGF transport out of the vascular compartment, localizing the IGFs to specific cell types, and modulating both IGF binding to receptors and growth-promoting actions. The functions of IGFBPs appear to be altered by posttranslational modifications. IGFBP-3, -4, -5, and -6 have been shown to be glycosylated. Likewise all the IGFBPs have a complex disulfide bond structure that is required for maintenance of normal IGF binding. IGFBP-2, -3, -4, and -5 are proteolytically cleaved, and specific proteases have been characterized for IGFBP-3, -4, and -5. Interestingly, attachment of IGF-I or II to IGFBP-4 results in enhancement of proteolysis, whereas attachment of either growth factor to IGFBP-5 results in inhibition of proteolytic cleavage. Cleavage of IGFBP-3 results in the appearance of a 31 kDa fragment that is 50-fold reduced in its affinity for the IGF-I or IGF-II. In spite of the reduction in its affinity, this fragment is capable of potentiating the effect of IGF-I on cell growth responses; therefore, proteolysis may be a specific mechanism that alters IGFBP modulation of IGF actions. Other processes that result in a reduction in IGF binding protein affinity are associated with potentiation of cellular responses to IGF-I and -II. Specifically, the binding of IGFBP-3 to cell surfaces is associated with its ability to enhance IGF action and with a ten- to 12-fold reduction in its affinity for IGF-I and IGF-II.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1993 Aug
PMID:IGF binding proteins and their functions. 769 Oct 98

Recent observations suggest that the diverse actions of the insulin-like growth factors (IGFs) are the result of interactions of the various components that make up the IGF system. The components of this system include IGF-I and -II and their variants, the type 1 and 2 IGF receptors and the insulin-like growth factor binding proteins (IGFBPs). Various components of the IGF system are expressed in the developing mouse embryo and the adjacent tissues of the reproductive tract in which the embryo develops. Thus there is the potential for paracrine interactions between the maternal and fetal tissues. Transcripts for the IGF receptors, IGF-I and IGF-II, have been demonstrated in the periimplantation mouse embryo. While there are now data from gene ablation experiments indicating that IGF-II is important in embryogenesis, the role of other components of the IGF system such as the IGFBPs remains unclear. The data accumulated so far are largely empirical, and there is as yet little compelling evidence that maternal IGFs derived from oviduct or uterine fluid and maternal tissues are necessary for normal fetal development. We have started to develop transgenic mice lines overexpressing IGFBPs to attempt to address the role of these binding proteins in fetal development.
Mol Reprod Dev 1993 Aug
PMID:The IGFs and their binding proteins in murine development. 769 Oct 99

The three-dimensional structure of human insulin-like growth factor (IGF) II in aqueous solution at pH 3.1 and 300 K has been determined from nuclear magnetic resonance data and restrained molecular dynamics calculations. Structural constraints consisting of 502 NOE-derived distance constraints, 11 dihedral angle restraints, and three disulfide bridges were used as input for distance geometry calculations in DIANA and X-PLOR, followed by simulated annealing refinement and energy minimization in X-PLOR. The resulting family of 20 structures was well defined in the regions of residues 5 to 28 and 41 to 62, with an average pairwise root-mean-square deviation of 1.24 A for the backbone heavy-atoms (N, C2, C) and 1.90 A for all heavy atoms. The poorly defined regions consist of the N and C termini, part of the B-domain, and the C-domain loop. Resonances from these regions of the protein gave stronger cross peaks in two dimensional NMR spectra, consistent with significant motional averaging. The main secondary structure elements in IGF-II are alpha-helices encompassing residues 11 to 21, 42 to 49 and 53 to 59. A small anti-parallel beta-sheet is formed by residues 59 to 61 and 25 to 27, while residues 26 to 28 appear to participate in intermolecular beta-sheet formation. The structure of IGF-II in the well-defined regions is very similar to those of the corresponding regions of insulin and IGF-I. Significant differences between IGF-II and IGF-I occur near the start of the third helix, in a region known to modulate affinity for the type 2 IGF receptor, and at the C terminus. The IGF II structure is discussed in relation to its binding sites for the insulin and IGF receptors and the IGF binding proteins.
J Mol Biol 1995 Apr 28
PMID:Solution structure of human insulin-like growth factor II. Relationship to receptor and binding protein interactions. 773 48

The cerebrospinal fluid (CSF) contains the same proteins as blood plasma, but with a different pattern of concentrations. Protein concentrations in CSF are much lower than those in blood. CSF proteins are derived from blood or synthesized within the brain. The choroid plexus is an important source of CSF proteins. Transthyretin is the protein most abundantly synthesized and secreted by choroid plexus. It determines the distribution of thyroxine in the cerebral compartment. Synthesis of transthyretin first evolved in the brain, then later it became a plasma protein synthesized in the liver. Other proteins secreted by choroid plexus are serum retinol-binding protein, transferrin, caeruloplasmin, insulin-like growth factors, insulin-like growth factor binding proteins, cystatin C, alpha 1-antichymotrypsin, alpha 2-macroglobulin, prothrombin, beta 2-microglobulin and prostaglandin D synthetase. Species differences in expression of the genes for these proteins are outlined, and their developmental pattern, regulation and roles in the cerebral extracellular compartment are discussed.
Comp Biochem Physiol B Biochem Mol Biol 1995 May
PMID:The cerebral expression of plasma protein genes in different species. 774 30


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