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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastrin-releasing polypeptide (GRP) has been implicated in the development of the human fetal lung. To determine whether GRP has a wider role in fetal development, its actions on DNA synthesis and cell replication by isolated epiphyseal growth plate chondrocytes obtained from ovine fetuses between 35 days gestation and near term (145 days) were examined. Chondrocytes were isolated using collagenase from the proximal tibia and cultured in monolayer. Synthesis of DNA was assessed from the incorporation of [3H]thymidine into previously growth-restricted cells after incubation in medium supplemented with GRP1-27 (40-1280 nM). Increase in cell number was assessed after incubation with test medium for 1 week. GRP caused a dose-dependent increase in both cell number and DNA synthetic rate compared to control incubations. Cell number was increased by 50% in the presence of a maximally effective 160 nM GRP and DNA synthesis by up to 800% utilizing chondrocytes obtained from animals of 75-80 days gestation. The mean (+/- SEM) half-maximal concentration of GRP for the stimulation of DNA synthesis was 97 +/- 12 nM (5 separate fetuses). Concentrations of GRP in excess of 160 nM caused a sharp reduction in both cell replication and DNA synthesis. To determine where within the cell cycle GRP exerted its mitogenic action, synchronized chondrocytes were transiently exposed to fetal bovine serum and cultured with GRP for increasing periods of time before pulse labeling with [3H]thymidine during S phase. GRP was as effective in stimulating DNA synthesis when present for the initial 4 h of G1 as when present for the entire G1 period. Since isolated fetal growth plate chondrocytes release insulin-like growth factor II (IGF II) and basic fibroblast growth factor (basic FGF) the possible mediation of GRP action by the release of these peptides or synergistic interactions were examined. Specific antibodies shown to negate the mitogenic actions of exogenous IGFs or basic FGF on chondrocytes did not alter GRP-stimulated DNA synthesis. The release of radioimmunoassayable IGF II by chondrocytes was not altered in the presence of GRP. Coincubation of GRP with submaximal concentrations of IGF I or basic FGF showed additive effects on DNA synthesis. When the actions of galanin were examined it was found to inhibit basal DNA synthesis by chondrocytes at a concentration of 167 nM. However, 66 nM or greater galanin was able to render 160 nM GRP inactive as a mitogen. These results suggest that GRP may potentially influence skeletal development in the ovine fetus and may interact with locally released peptide growth factors or other neuropeptides.
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PMID:Mitogenic action of gastrin-releasing polypeptide on isolated epiphyseal growth plate chondrocytes from the ovine fetus. 157 94

The migration of retinal pigment epithelial (RPE) cells from their normal anatomic position to a new position in the vitreous cavity is a critical feature of proliferative vitreous retinopathy. To determine if insulin-like growth factor I (IGF I), which is present in the vitreous fluid of diabetics, stimulates RPE cells, we examined the effects of IGF I on the proliferation, chemotaxis, and release of plasminogen activator by these cells. At the concentrations of IGF I tested, significant proliferation of RPE cells is seen. Significant chemotaxis of the RPE cells also is seen at all the concentrations of IGF I tested. The mean number of migrating cells per high-powered field in control studies was 43 +/- 13 (x +/- SEM), and for IGF I at 2.5 ng and 50 ng/ml the mean numbers of migrating cells were 96 +/- 17 and 483 +/- 62, respectively (P less than 0.001 for each comparison). The IGF I response was noted to be dose-dependent. The chemotactic response noted at 50 ng/ml of IGF I was greater than the positive chemotactic control of 10% fetal calf serum. Addition of alpha IR-3, an IGF I receptor antibody, eliminated the IGF I chemotactic response. The effect of IGF I on the secretion of plasminogen activators was assessed using an immunological assay for tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI). Media conditioned by RPE cells have measureable levels of PAI and t-PA antigen. IGF I supplementation resulted in an increase of t-PA secretion and PAI secretion over basal levels. These studies support a role for IGF I in modulating RPE cell function.
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PMID:Insulin-like growth factor I stimulates proliferation, migration, and plasminogen activator release by human retinal pigment epithelial cells. 211 Dec 35

Somatomedin C/IGF I, dehydroepiandrosterone sulfate (DHAS), testosterone (T) or estradiol (E2) have been measured in 154 patients of a previous study in which growth hormone (GH) responses to classical pharmacologic stimuli and spontaneous growth hormone secretion during sleep were compared in short children before and at the beginning of puberty. Five groups were identified: Group I, normal growth hormone secreting children; group II, completely growth hormone deficient; group III, partially growth hormone deficient; group IV, with normal sleep secretion and low responses to stimuli; group V, with the reverse situation. The somatomedin C/IGF I levels were widely dispersed. In group I, the mean +/- SEM levels of somatomedin C/IGF I were 0.77 +/- 0.047 U/ml before puberty and 1.36 +/- 0.142 U/ml in early pubertal patients, with a relation to age (r = 0.52, p less than 0.001). The difference between prepubertal and pubertal patients was significant. In groups II to V, there was no pubertal rise of somatomedin C/IGF I. In group II, the mean IGF I level was 0.48 +/- 0.05 U/ml, significantly lower than in prepubertal patients of group I. In groups III, IV and V, it was 0.7 +/- 0.069 U/ml, 0.8 +/- 0.059 U/ml, and 0.73 +/- 0.059 U/ml respectively, not different from prepubertal patients of group I, but significantly lower than in early pubertal patients of the same group. In prepubertal patients, somatomedin C/IGFI was slightly but highly significantly correlated to the growth hormone sleep secretion (r = 0.27, p less than 0.001) and to dehydroepiandrosterone sulfate (r = 0.36, p less than 0.001), but growth hormone and dehydroepiandrosterone sulfate were not correlated together.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Relation of the secretion of growth hormone (GH), somatomedin C/IGF I (IGF I) and steroids before and after the beginning of puberty in patients of short stature]. 213 77

Somatomedin C/IGF I, dehydroepiandrosterone sulfate (DHAS), testosterone (T) or estradiol (E2) have been measured in 154 patients of a previous study in which growth hormone (GH) responses to classical pharmacologic stimuli and spontaneous growth hormone secretion during sleep were compared in short children before and at the beginning of puberty. Five groups were identified: Group I, normal growth hormone secreting children; group II, completely growth hormone deficient; group III, partially growth hormone deficient; group IV, with normal sleep secretion and low responses to stimuli; group V, with the reverse situation. The somatomedin C/IGF I levels were widely dispersed. In group I, the mean +/- SEM levels of somatomedin C/IGF I were 0.77 +/- 0.047 U/ml before puberty and 1.36 +/- 0.142 U/ml in early pubertal patients, with a relation to age (r = 0.52, p less than 0.001). The difference between prepubertal and pubertal patients was significant. In groups II to V, there was no pubertal rise of somatomedin C/IGF I. In group II, the mean IGF I level was 0.48 +/- 0.05 U/ml, significantly lower than in prepubertal patients of group I. In groups III, IV and V, it was 0.7 +/- 0.069 U/ml, 0.8 +/- 0.059 U/ml, and 0.73 +/- 0.059 U/ml respectively, not different from prepubertal patients of group I, but significantly lower than in early pubertal patients of the same group. In prepubertal patients, somatomedin C/IGF I was slightly but highly significantly correlated to growth hormone sleep secretion (r = 0.27, p less than 0.001) and to dehydroepiandrosterone sulfate (r = 0.36, p less than 0.001), but growth hormone and dehydroepiandrosterone sulfate were not correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The relation between the secretion of growth hormone (GH), somatomedin C/IGF I (IGF I) and steroids before and after the onset of puberty in patients of small stature]. 214 88

The effects of a physiological dose of IGF I (40 ng/ml approximately 5 x 10(-9) M) on steroidogenesis were studied in bovine adrenal fasciculata cells cultured in serum-free McCoy's medium. They were compared with those of a single dose of ACTH (0.25 ng/ml approximately 10(-10) M) at approximately the concentration inducing half-maximal stimulation. With IGF I, steroidogenesis commenced after 48 h culture and progressively increased throughout the 96-h test period. Expressed as stimulated level/control level ratios, glucocorticoid (cortisol + corticosterone) responses to IGF I after 4 days' culture (2.41 +/- 0.20 (SEM) n = 9) were similar to those obtained with ACTH (2.59 +/- 0.18, n = 9). A combination of the two peptides had a synergistic effect (5.95 +/- 0.79, n = 5). The cortisol/corticosterone ratio increased in the presence of IGF I from 1 +/- 0.19 to 1.76 +/- 0.45 (n = 7, P less than 0.02), although less so than in the presence of ACTH (5.50 +/- 0.98). Moreover, cortisol production was accompanied by androstenedione production (2.36 ng/10(6) cells, n = 3) similar to that induced by ACTH (2.10 ng/10(6) cells, n = 3). These findings together suggest stimulation of 17 alpha-hydroxylase activity. Cell multiplication was unaffected by IGF I. [3H]Thymidine incorporation into DNA reached only 193% +/- 17 (SEM) (n = 4) of control levels, whereas with ACTH it dropped to 60% +/- 5. Our findings show that IGF I alone has no mitogenic effect on adrenocortical cells in vitro, but that it is capable of inducing differentiated steroidogenesis.
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PMID:Insulin-like growth factor I (IGF I) induces cortisol production in bovine adrenocortical cells in primary culture. 217 Jul 67

Serum insulin-like growth factor (IGF) and IGF-binding protein (IGF BP) levels were determined in 13 insulin-dependent diabetic patients (30-60 yr of age) during an episode of severe metabolic decompensation and the recovery phase. After separation by acidic gel filtration, the samples were assayed for IGF using a protein-binding assay (which measures mainly IGF I-related peptides) and for IGF BP by measuring the binding activity, in both assays using IGF I as tracer. The reference standard was a pool of normal adult serum with an assigned potency of 1 U IGF and 1 U IGF BP per ml. The mean IGF level in the uncontrolled state, 0.55 +/- 0.05 (SEM) U/ml, was about half that of normal subjects (1.03 +/- 0.03 U/ml, P less than 0.001). With treatment, IGF levels reached the normal range within 3 days. The pattern of changes in IGF BP levels was roughly similar, although the values in the uncontrolled state were less depressed (0.78 +/- 0.04 U/ml vs. 0.98 +/- 0.04 in normal subjects, P less than 0.01). Highly significant correlations (P less than 0.001) were found between IGF levels and the biological parameters reflecting control of the diabetes: glycosuria (r = -0.60), glycemia (r = -0.52), ketonemia (r = -0.65), and HCO3- (r = 0.58). Similar but less significant correlations were found for IGF BP. The mean GH level during the period of metabolic decompensation (9.0 +/- 1.5 ng/ml) was elevated compared to that after recovery (2.9 +/- 0.8 ng/ml) (P less than 0.025). There was a negative correlation between GH values and IGF levels (r = -0.67, P less than 0.001). The correlation with IGF BP was much less significant (r = -0.38, P less than 0.05). The results clearly reflect the role of insulin and nutritional factors in the control of IGF levels. They also support the notion that the biosynthesis of IGF and IGF BP is not regulated in the same way.
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PMID:Serum levels of insulin-like growth factor (IGF) and IGF binding protein in insulin-dependent diabetics during an episode of severe metabolic decompensation and the recovery phase. 257 89

We have investigated whether the previously demonstrated stimulatory actions of growth hormone on DNA synthesis and (pro)insulin biosynthesis and release of isolated adult rat islets of Langerhans are mediated by an autocrine release of somatomedin-C/insulin-like growth factor I (SM-C/IGF I). In medium containing 1% fetal calf serum, the presence of 16.7 mmol/l glucose, or 2.7 mmol/l glucose supplemented with a concentrate of essential amino acids, caused a significant increase in 3H-thymidine incorporation and insulin release compared to 2.7 mmol/l glucose alone but no increase in SM-C/IGF I release. Further supplementation with 1 microgram/ml growth hormone increased 3H-thymidine incorporation and SM-C/IGF I release within all groups, and insulin release in the 16.7 mmol/l glucose and 2.7 mmol/l plus amino acid groups. The ability of growth hormone to increase 3H-thymidine incorporation in the presence of 16.7 mmol/l glucose, but not its action on insulin release, was partly inhibited by a monoclonal antibody against SM-C/IGF I (control cultures 100%; growth hormone alone 261 +/- 27%, mean +/- SEM; growth hormone + anti-SM-C/IGF I 179 +/- 21%; p less than 0.05, n = 18). Growth hormone, but not 100 ng/ml SM-C/IGF I, increased insulin biosynthesis assessed as immunoprecipitable 3H-labelled insulin by 45%, but this was accompanied by a similar increase in overall protein synthesis. Similarly growth hormone, but not SM-C/IGF I caused a 75% increase in glucose oxidation by islets. Both growth hormone and SM-C/IGF I failed to increase the cellular uptake of alpha-aminoisobutyric acid or 3-O-methyl glucose over a 90 min period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone regulation of DNA replication, but not insulin production, is partly mediated by somatomedin-C/insulin-like growth factor I in isolated pancreatic islets from adult rats. 266 10

The rise in serum IGF I concentration during continuous subcutaneous insulin infusion (CSII) may be a contributory factor in the deterioration of diabetic retinopathy that sometimes occurs during this treatment but the relation of serum levels to the severity of retinopathy has not been previously studied. In twelve non-obese insulin dependent diabetics (age range: 22-41 yrs) with mean +/- SD duration of diabetes: 14.8 +/- 4.7 yrs, serum IGF I concentration, HbA1 and retinopathy score were estimated prospectively over twelve months following the institution of CSII therapy. After four months of treatment, eight patients showed deterioration of retinopathy by at least one level of severity. Serum IGF I concentration rose from a mean +/- SEM of 155 +/- 17.7 micrograms/l at entry to 199 +/- 23.1 micrograms/l at four months and by twelve months had returned to near initial values 163 +/- 17.4 micrograms/l. There was however, no significant correlation between retinopathy score and serum IGF I level by analysis of variance for the whole group, or in the group of diabetics whose retinopathy deteriorated. The rise in IGF I concentration over the first four months and subsequent decline in IGF I values over the next eight months was inversely related to HbA1 concentration (r = -0.58; P less than 0.05). One patient with early ischaemic retinopathy on entry, experienced a marked rise in serum IGF I corresponding to a rapid tightening of glycaemic control. At four months she developed florid proliferative changes requiring panretinal laser therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Progression of diabetic retinopathy and changes in serum insulin-like growth factor I (IGF I) during continuous subcutaneous insulin infusion (CSII). 292 51

The temporal relationships between the changes in inulin and p-aminohippurate clearances and plasma growth hormone (GH) and insulin-like growth factor I (IGF I levels were examined in a man with hypothalamic GH deficiency before and during the first 6 days of treatment with daily GH injections. The patient ate a diet with a constant protein and salt content from 1 week before the study until it was completed. During the 4-hour period immediately after the first GH injection, plasma GH rose markedly, but plasma IGF I was not detectable, and effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) did not change from baseline. On the next day, before the second GH injection was given, plasma GH was only slightly elevated, plasma IGF I had increased, and ERPF and GFR had risen by +35.5 +/- 2.1% (SEM) and +22.7 +/- 2.8%, respectively. On the 4th and 7th days, immediately before the GH injections, there was no further rise in ERPF and GFR, both of which remained well above baseline values. At these times, plasma GH levels were at baseline, but plasma IGF I continued to rise progressively. These data are consistent with the thesis that the low ERPF and GFR in GH deficiency is due to the lack of synthesis of IGF I rather than the deficiency in GH per se. The data are also consistent with a stimulatory effect of IGF I on ERPF and GFR.
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PMID:Increase in renal plasma flow and glomerular filtration rate during growth hormone treatment may be mediated by insulin-like growth factor I. 323 97

To investigate the possible role of somatomedin-C/insulin-like growth factor I (Sm-C/IGF I) in early human development, we measured this peptide by radioimmunoassay in extracts of multiple tissues and in plasma from fetuses during the first half of gestation (9-19 wk). All tissues contained Sm-C/IGF I far in excess of that which could be accounted for by Sm-C/IGF I derived from blood entrapment. Lung and intestine had the highest concentrations (166 +/- 35 mU/g, n = 25 and 160 +/- 20 mU/g, n = 19, respectively; mean +/- SEM) and liver the lowest (67 +/- 16 mU/g, n = 26). Plasma concentrations were 270 +/- 20 mU/ml (n = 20). Neither fetal weight (6-258 g) nor gestational age correlated with Sm-C/IGF I concentrations in any tissue or in plasma. These findings suggest that Sm-C/IGF I is synthesized in many human fetal tissues from as early as the 1st trimester. They also provide further evidence for an autocrine/paracrine role of this peptide growth factor.
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PMID:Tissue and plasma somatomedin-C/insulin-like growth factor I concentrations in the human fetus during the first half of gestation. 370 13


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