A F Bristow, R Gaines-Das, S L Jeffcoate, D Schulster
{"title":"The First International Standard for Somatropin: report of an international collaborative study.","authors":"A F Bristow, R Gaines-Das, S L Jeffcoate, D Schulster","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Following an earlier decision to move away from the in vivo bioassay for determination of the potency of therapeutic somatropin (recombinant DNA human growth hormone), 18 laboratories in 12 countries participated in an international collaborative study designed to establish an international standard for somatropin, calibrated both by bioassay and by physicochemical assays of somatropin content. The mean in vivo biological potency of preparation studied, coded 88/624, was 6.75 IU/ampoule (fiducial limits 6.30-7.23). Determination of the protein content by quantitative amino-acid analysis yielded a mean estimate of 1.98 mg protein per ampoule. (Relative standard deviation = 2.88%). Data from the study also yielded mean values of 97.2% +/- 0.8% for the monomer content of the preparation, and 8.18 (RSD = 4.00%) for A1% at 276 nm. At its 45th meeting, in October 1994, the ECBS of WHO formally established the preparation 88/624 as the First International Standard for Somatropin, with a defined content of 2.0 mg protein per ampoule, and a defined specific activity of 3.0 International Units per milligram.</p>","PeriodicalId":77148,"journal":{"name":"Growth regulation","volume":"5 3","pages":"133-41"},"PeriodicalIF":0.0,"publicationDate":"1995-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18586657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of IGF-I in the control of GH secretion in rainbow trout (Oncorhynchus mykiss).","authors":"O Blaise, C Weil, P Y Le Bail","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To study the role of IGF-I on GH secretion, we looked firstly for IGF-I binding sites in the central nervous system. IGF-I presents a single class of binding sites on brain membranes and pituitary extracts. Their affinity constants (Ka) were 11.44 +/- 4.66 and 4.42 +/- 1.37 x 10(9) M-1, respectively and their capacity (Bmax) were 119.83 +/- 46.21 and 73.65 +/- 20.87 fmoles/mg, respectively. In a second step IGF-I and bGH action on GH release was tested in vitro and in vivo. IGF-I inhibited GH release by pituitary cell cultures while bGH did not, suggesting direct action of IGF at the pituitary level and indirect action of GH, possibly mediated by IGF-I. IGF-I injected into catheterization fish induced a rapid inhibition of GH release, while bGH induced a delayed one. This timing supports a direct effect of IGF-I on GH release and the indirect effect of bGH. So peripheral IGF-I can play a role on GH secretion, perhaps as a mediator of GH action. This could explain the delayed fluctuation of GH and IGF-I plasma levels previously observed. This strong relationship between plasma IGF and GH secretion in trout seems to be different from that in mammals in which systemic IGF does not seem to play a predominant role in regulating GH secretion.</p>","PeriodicalId":77148,"journal":{"name":"Growth regulation","volume":"5 3","pages":"142-50"},"PeriodicalIF":0.0,"publicationDate":"1995-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18586658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T Hasegawa, P Cohen, Y Hasegawa, P J Fielder, R G Rosenfeld
{"title":"Characterization of the insulin-like growth factors (IGF) axis in a cultured mouse Leydig cell line (TM-3).","authors":"T Hasegawa, P Cohen, Y Hasegawa, P J Fielder, R G Rosenfeld","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Characterization of the insulin-like growth factor (IGF) axis in a cultured mouse Leydig cell line (TM-3) was performed. Radioimmunoassayable IGF-I and IGF-II concentrations in TM-3 conditioned media (CM) were below the assay detection levels. Affinity cross-linking of IGF-I and IGF-II to crude membranes prepared from TM-3 cells revealed both type 1 and type 2 receptors and a 31 kDa IGF binding protein (IGFBP). Immunoprecipitation of solubilized crude membranes indicated that the 31 kDa protein was membrane associated IGFBP-4. Western ligand blots of CM from TM-3 cells demonstrated the presence of 24 and 28 kDa bands as major IGFBPs, and 25, 40, and 44 kDa as minor ones. The 28 kDa band could be invisible after Endoglycosidase-F treatment, suggesting that the 28 kDa IGFBP was a glycosylated form of IGFBP. The 24 kDa and 28 kDa bands were immunoprecipitated with an antibody to IGFBP-4. Treatment of TM-3 cells with IGF-I increased the levels of the 24 kDa IGFBP-4, as well as 25, 28, 40, and 44 kDa IGFBPs. IGF-I treatment also resulted in the appearance of a 29 kDa IGFBP. Neither the 25 nor 29 kDa bands were deglycosylated with Endoglycosidase-F nor immunoprecipitated by antibodies to rIGFBP-1 and -2. On the other hand, IGF-II treatment resulted in a significant decrease in the 24 kDa IGFBP-4.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77148,"journal":{"name":"Growth regulation","volume":"5 3","pages":"151-9"},"PeriodicalIF":0.0,"publicationDate":"1995-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18588007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Increased plasma insulin-like growth factor-I (IGF-I) following oral and intraperitoneal administration of growth hormone to rainbow trout, Oncorhynchus mykiss.","authors":"S Moriyama","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Changes in plasma insulin-like growth factor-I (IGF-I) and growth hormone (GH) levels in rainbow trout, Oncorhynchus mykiss, were investigated after either intraperitoneal or oral (intragastric) administration of salmon GH. Plasma IGF-I and GH levels were measured by homologous radioimmunoassays for salmon IGF-I and GH. After intraperitoneal injection of salmon GH at doses of 0.1 or 1.0 micrograms/g body weight to rainbow trout, plasma GH levels increased to a maximum after 6 h and declined rapidly thereafter. Plasma IGF-I levels were elevated after 12 h, reaching maximum at 24 h and (after the higher dose of GH) remaining high at 78 h after GH injection. In contrast, following intragastric administration of salmon GH at the same doses, plasma GH levels were significantly elevated 12 h after administration, reaching a maximum at 15 h and declining to basal levels at 24 h. Plasma IGF-I levels increased significantly after 48 h and remained elevated (after the higher dose of GH) for more than 96 h. Effects on plasma GH and IGF-I were dose-dependent notwithstanding the route of administration of GH. These results indicate that plasma IGF-I in salmonid fish is under GH control and that oral administration of the hormone is followed by longer-lasting effects than those achieved by intraperitoneal injection.</p>","PeriodicalId":77148,"journal":{"name":"Growth regulation","volume":"5 3","pages":"164-7"},"PeriodicalIF":0.0,"publicationDate":"1995-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18588009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects on neonatal growth of the Hba(th-j) deletion on mouse chromosome 11 are not due to genomic imprinting.","authors":"J A Hendrey, M Dziadek","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The Hba(th-j) deletion is found proximally on mouse chromosome 11 in a region of the genome that contains imprinted sequences important for neonatal growth regulation. This study has examined the effect of genomic imprinting on neonatal growth of offspring heterozygous for the Hba(th-j) deletion. Transmission of the deletion through both the male and female germ lines has shown that offspring heterozygous for the deletion are growth retarded when compared to wild type litter mates. This growth retardation is associated with the heterozygous genotype regardless from which parent the deletion is inherited. Growth of both wild type and Hba(th-j)/+ neonates born from Hba(th-j)/+ mothers is compromised when compared to offspring from wild type mothers indicating a maternal effect of the deletion on neonatal growth. These data demonstrate that sequences present in the Hba(th-j) deletion are important for growth regulation but that the expression of these sequences is not regulated by genomic imprinting.</p>","PeriodicalId":77148,"journal":{"name":"Growth regulation","volume":"5 3","pages":"160-3"},"PeriodicalIF":0.0,"publicationDate":"1995-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18588008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acromegaly: unravelling a complex disease.","authors":"D J O'Halloran, S M Shalet","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acromegaly is a rare endocrine disorder characterized by growth hormone hypersecretion and is usually caused by a pituitary macroadenoma. It is associated with significantly increased patient morbidity and mortality. Molecular biological studies have implicated a causative role for oncogenic mutations (activating Gs alpha mutations and/or chromosomal 11q13 deletions) in less than 50% of cases. The cause(s) in the remaining 50% is speculative. Epidemiological evidence indicates that biochemical cure is achieved when mean GH levels are 5mU/l or less during a day-profile. This GH value correlates well with that required to normalize the serum IGF-1 concentration, a GH-dependent peptide which can be used to monitor the disease activity in acromegaly. Treatment must be carried out under the supervision of a dedicated endocrinologist and tailored to patients needs. The success of any treatment modality (surgery/pituitary irradiation/medical) depends on adenoma size and the extent of pretreatment GH hypersecretion. A combination of therapies is usually required to achieve satisfactory control of adenoma growth and GH hypersecretion. Octreotide, a synthetic analogue of native somatostatin, is particularly effective in controlling GH hypersecretion in this condition and the widespread introduction of a long-acting depot preparation is eagerly awaited. The development of true GH deficiency as a result of treatment is potentially worrying in view of its possible contribution to the increased incidence of cardiovascular mortality associated with hypopituitarism.</p>","PeriodicalId":77148,"journal":{"name":"Growth regulation","volume":"5 3","pages":"119-24"},"PeriodicalIF":0.0,"publicationDate":"1995-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18586655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S M Muaku, L E Underwood, P L Selvais, J M Ketelslegers, D Maiter
{"title":"Maternal protein restriction early or late in rat pregnancy has differential effects on fetal growth, plasma insulin-like growth factor-I (IGF-I) and liver IGF-I gene expression.","authors":"S M Muaku, L E Underwood, P L Selvais, J M Ketelslegers, D Maiter","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We determined whether the effects of maternal protein restriction at various stages of pregnancy on fetal growth are accompanied by parallel changes in the expression of insulin-like growth factor (IGF)-I and -II in the fetal rat. Pregnant Wistar rats (5-7 per group) fed a low (5%) protein diet throughout gestation or during the last week only of gestation had decreased body weight gain, serum IGF-I, and liver IGF-I peptide and mRNA concentrations compared to control dams fed a normal (20%) protein diet. In contrast, dietary protein restriction during the first 2 weeks followed by the normal diet during the last week of pregnancy had no effect on these maternal indices at term. Pups born from dams fed the low protein diet during the last week only (P5-3d week pups) or throughout gestation (P5-pups) had lower birth weight (-11%; P < 0.05, and -22%; P < 0.001, respectively) and lower liver weight (-13%; P < 0.05, and -29%; P < 0.001) than control pups (P20-pups). Plasma IGF-I, liver IGF-I, and liver IGF-I mRNA concentrations were reduced in both P5-3d week pups (by 34%, 31% and 26%, respectively) and P5-pups (by 56%, 66% and 44%, respectively). In contrast, short- or long-term maternal protein restriction had no effect on neonatal plasma IGF-II peptide and liver IGF-II mRNA concentrations. When imposed only during the first 2 weeks of gestation, maternal protein restriction had no effect on growth or IGF-I and IGF-II expression in newborn pups.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77148,"journal":{"name":"Growth regulation","volume":"5 3","pages":"125-32"},"PeriodicalIF":0.0,"publicationDate":"1995-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18586656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transcriptional regulation of insulin-like growth factor binding protein-1 expression by insulin and cyclic AMP.","authors":"S Babajko","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In biological fluids, insulin-like growth factor binding proteins (IGFBPs) interact with the IGFs and modulate their effects. In this study, changes in IGFBP-1 expression were investigated under the influence of insulin and cAMP which may regulate expression of the IGFBP-1 gene in vivo during the perinatal period. Western ligand blot analysis of IGFBPs secreted by HepG2 human hepatoma cells showed that 24 h treatment with forskolin increased IGFBP-1 secretion by approximately 100%, whereas similar treatment with insulin resulted in a 50% reduction. After 24 h, the amounts of IGFBP-1 mRNA (measured by Northern blotting) were increased 2.5 times by forskolin and decreased by 65% by insulin. Transient transfection experiments showed that forskolin enhanced IGFBP-1 promoter activity by 70%, suggesting that stimulation of IGFBP-1 gene expression by cAMP is transcriptional, via a protein recognizing the cAMP responsive element (CRE) consensus sequence (nt -268 to -248). In contrast, modulation of gene expression by insulin is more complex, probably involving several levels of regulation. Complementary experiments (site-directed mutagenesis and/or use of a heterologous promoter) will be needed to confirm the functionality of the proteins interacting with the IRE (nt -285 and -276) and the CRE (between nt -268 and -248) described.</p>","PeriodicalId":77148,"journal":{"name":"Growth regulation","volume":"5 2","pages":"83-91"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18549117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F G Conti, R Powell, L Pozzi, G Zezze, T Faraggiana, F Gannon, A Fabbrini
{"title":"A novel line of transgenic mice (RSV/LTR-bGH) expressing growth hormone in cardiac and striated muscle.","authors":"F G Conti, R Powell, L Pozzi, G Zezze, T Faraggiana, F Gannon, A Fabbrini","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In order to further investigate the deleterious effects of GH overexpression, we generated a novel line of transgenic mice featuring stable and specific expression of bovine GH in the heart and striated muscle. A DNA construct, containing a region with promoter activity from the Long Terminal Repeat of Rous Sarcoma Virus (RSV-LTR) and the entire structural gene of bovine GH (bGH), was microinjected by standard techniques in male pronuclei of fertilized mice eggs. Transgenic mice expressed bGH mRNA in the heart and striated muscle starting at 5-6 weeks of age. They featured circulating levels of a 22 kDa form of bGH up to 700 ng/ml and enhanced growth starting at 6 weeks of age. No pathologic changes of the myocardium and striated muscle fibers, other than hypertrophy, were noticed, although severe glomerulosclerosis and liver alteration occurred in older mice. Future studies on this new line of transgenic GH mice and integration with the existing data might improve our understanding of the molecular mechanism underlying the detrimental effects of elevated GH levels on various organs and functions.</p>","PeriodicalId":77148,"journal":{"name":"Growth regulation","volume":"5 2","pages":"101-8"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18633301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Activation of MAP kinase in Swiss 3T3 fibroblasts by insulin-like growth factor-I.","authors":"A Hansson, M Thorén","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A peak of cytosolic myelin basic protein kinase activity was observed at 2-5 min after addition of 10 nM insulin-like growth factor-I (IGF-I) to Swiss 3T3 fibroblasts. Analysis of the induced kinase activity by chromatography, immunodetection and in situ kinase assay suggests that this represents a 1.8- to 3.5-fold increase in the activity of p42 mitogen-activated protein kinase. Addition of insulin at 10 nM also resulted in an increased kinase activity in these respects, however, only to approximately 60% of that induced by IGF-I. A similar quantitative relation between the effects of insulin and IGF-I was found for induction of lipid and glycogen synthesis from [14C- (U)]-D-glucose. However, incorporation of 3H-L-leucine into protein was stimulated to the same extent by the two agents. The effect of 10 nM insulin on proliferation, measured as tetrazolium dye reduction, was only 18% of that induced by 10 nM IGF-I. The obtained data suggest that cytosolic mitogen-activated protein kinase activation may constitute a signalling pathway for glucose metabolism, and especially glycogen synthesis, induced by peptides of the insulin superfamily.</p>","PeriodicalId":77148,"journal":{"name":"Growth regulation","volume":"5 2","pages":"92-100"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18633303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}