IGF-I Immunoreactivity Research Articles

Altered expression of IGF-I system in neurons of the inflamed spinal cord during acute experimental autoimmune encephalomyelitis.

There is growing evidence that the impaired IGF-I system contributes to neurodegeneration. In this study, we examined the spinal cords of the EAE, the animal model of multiple sclerosis, to see if the expression of the IGF-I system is altered. To induce EAE, C57/BL6 mice were immunized with the Hooke lab MOG kit, sacrificed at the peak of the disease and their spinal cords were examined for the immunoreactivities (ir) of the IGF-I, IGF binding protein-1 (IGFBP-1) and glycogen synthase kinase 3β (GSK3β), as one major downstream molecule in the IGF-I signaling. Although neurons in the non EAE spinal cords did not show the IGF-I immunoreactivity, they were numerously positive for the IGFBP-1. In the inflamed EAE spinal cord however, the patterns of expressions were reversed, that is, a significant increased number of IGF-I expressing neurons versus a reduced number of IGFBP-1 positive neurons. Moreover, while nearly all IGF-I-ir neurons expressed GSK3β, some expressed it more intensely. Considering our previous finding where we showed a significant reduced number of the inactive (phosphorylated) but not that of the total GSK3β expressing neurons in the EAE spinal cord, it is conceivable that the intense total GSK3β expression in the IGF-I-ir neurons belongs to the active form of GSK3β known to exert neuroinflammatory effects. We therefore suggest that the altered expression of the IGF-I system including GSK3β in spinal cord neurons might involve in pathophysiological events during the EAE.

Immunohistochemical expression of growth factors in the follicular wall of normal and cystic ovaries of sows.

The expression of growth factors was evaluated immunohistochemically in normal and cystic ovaries of sows. The immunohistochemically stained area (IHCSA) was quantified by image analysis to analyse the expression of these proteins in the follicular wall of secondary, tertiary and cystic follicles. IGF-I immunoreactivity was strong in the granulosa cell layer (GC), moderate in the theca interna (TI) and mild in the theca externa (TE) of the normal follicles. There was severe reduction of the labelling to IGF-I in the GC of the follicular and luteinized cysts. In the normal follicles, the reactivity for IGF-II was very similar to pattern noted in IGF-I. There was reduction of the IHCSAs in the GC of the follicular and luteinized cysts, but the decrease was not significant. The staining of the IGF-II in the TI and TE of the cysts was increased, in comparison with normal follicles. The IHCSAs for VEGF were higher in the GC and TE of the normal follicles in contrast to TI, but this difference was noted only in the tertiary follicle. The VEGF reactivity increased in the GC of the cysts, in relation to normal follicles. The results of the current study show that the formation of ovarian cysts in sows is associated with alterations in the immunohistochemical expression of some growth factors.

The severe short stature in two siblings with a heterozygous IGF1 mutation is not caused by a dominant negative effect of the putative truncated protein

Objective While in previous studies heterozygosity for an Insulin-Like Growth Factor 1 ( IGF1) defect only modestly decreased height and head circumference, we recently reported on two siblings with severe short stature with a maternally transmitted heterozygous duplication of 4 nucleotides, resulting in a frame shift and a premature termination codon in the IGF1 gene. In this paper we describe the structural and functional characteristics of the putative truncated IGF-I protein. Design Two children, their mother and maternal grandfather carried the mutation. In addition, two family members who were not affected were included in the study. Mutant (MT) IGF-I was synthesized in oxidized and reduced form using two methods. Neutral gel filtration studies were carried out with wild-type (WT) and synthetic MT IGF-I. Binding analysis of synthetic MT IGF-I to the IGF1R and insulin receptors were performed with EBNA-293 cells, stably transfected with the IGF-I receptor, and IM9 cells. L6 cells were used to examine the mitogenic potency and the potential antagonizing effect of synthetic MT IGF-I by [ 3H]-thymidine incorporation assays. Results In the sera of both the carriers and non-carriers the proportion of 125I-IGF-I that was associated with the 150 kDa complex was somewhat less (varying between ~ 37 and ~ 52%) than in normal pooled serum (~ 53 − ~ 63%) and, instead, slightly increased amounts of radioactivity were eluted in the 40−50 kDa fraction (consisting of binary IGF–IGFBP complexes) or remained unbound. Synthetic MT IGF-I did not bind to the IGF-I receptor, nor antagonize the growth-promoting effect of IGF-I. It did bind to IGFBPs, but was barely incorporated into 150 kDa complexes. Because in all cases WT IGF-I immunoreactivity was recovered in one peak, corresponding to the MW of WT IGF-I, i.e. ~ 7.6 kDa, an interaction of circulating truncated mutant peptide with WT IGF-I is very unlikely. Conclusions There is no evidence that the severe short stature associated with heterozygosity for this novel IGF1 mutation in children born from a mother with the same mutation is caused by a dominant negative effect of the truncated protein. We speculate that the growth failure is caused by a combination of partial IGF-I deficiency, placental IGF-I insufficiency, and other genetic factors.

Immunohistochemical localization of IGF-I, IGF-II and MSTN proteins during development of triploid sea bass (Dicentrarchus labrax)

The cellular localization of IGF-I, IGF-II and MSTN proteins was investigated during ontogenesis of triploid sea bass (Dicentrarchus labrax) by an immunohistochemical approach. The results were compared with those observed in diploids. IGF-I immunostaining was mainly observed in skin, skeletal muscle, intestine and gills of both diploids and triploids. From day 30 of larval life, IGF-I immunoreactivity observed in skeletal muscle, intestine, gills and kidney was stronger in triploids than in diploids. At day 30, triploids exhibited a standard length significantly higher than the one of diploids. Although IGF-II and MSTN immunoreactivity was detectable in different tissues and organs, no differences between diploids and triploids were observed. The spatial localization of IGF-I, IGF-II and MSTN proteins detected in this study is in agreement with previous findings on the distribution of these proteins in diploid larvae and fry. The highest IGF-I immunoreactivity observed in triploids suggests a possible involvement of ploidy in their growth performance.

Effect of growth hormone on small intestinal homeostasis relation to cellular mediators IGF-I and IGFBP-3.

To evaluate the effects of growth hormone (GH) on the histology of small intestines which might be related to the role of insulin like growth factor (IGF)-I, IGF-binding protein 3 (IGFBP-3) and its receptors. Twelve week-old adult male Wistar albino rats were divided into two groups. The study group (n = 10), received recombinant human growth hormone (rGH) at a dose of 2 mg/kg per day subcutaneously for 14 d and the control group (n = 10) received physiologic serum. Paraffin sections of jejunum were stained with periodic acid shift (PAS) and hematoxylin and eosin (HE) for light microscopy. They were also examined for IGF-I, IGFBP-3 and IGF-receptor immunoreactivities. Staining intensity was graded semi-quantitatively using the HSCORE. Goblet cells and the cells in crypt epithelia were significantly increased in the study group compared to that of the control group. We have demonstrated an increase of IGF-I and IGFBP-3 immunoreactivities in surface epithelium of the small intestine by GH application. IGF-I receptor immunoreactivities of crypt, villous columnar cells, enteroendocrine cells and muscularis mucosae were also more strongly positive in the study group compared to those of in the control group. These findings confirm the important trophic and protective role of GH in the homeostasis of the small intestine. The trophic effect is mediated by an increase in IGF-I synthesis in the small intestine, but the protective effect is not related to IGF-I.

IGF binding protein alterations on periplaque oligodendrocytes in multiple sclerosis: Implications for remyelination

Why myelin repair greatly fails in multiple sclerosis (MS) is unclear. The insulin-like growth factor (IGF) system plays vital roles in oligodendrocyte development, survival, and myelin synthesis. We used immunohistochemistry to study IGF-I, IGF-I receptors and IGF binding proteins (IGFBPs) 1–6 on oligodendrocytes at the edges of chronic demyelinated plaques and normal appearing white matter of MS, and in cerebral white matter of controls without neurological disease. Oligodendrocytes in all conditions were immunoreactive for IGF-I, IGF-I receptors and IGFBPs-1–5. Oligodendrocytes at the edges of demyelinated plaques displayed enhanced immunoreactivity for IGF-I, IGF-I receptors, IGFBPs-1 and -6. Because increased expression of IGFBPs-1 and -6 has been associated with impaired synthesis of myelin proteins in oligodendrocyte lineage cells, pharmacological approaches to reduce their expression might be useful for promoting remyelination of axons in MS lesions.

Early glutamine-enriched enteral feeding facilitates colonic anastomosis healing: Light microscopic and immunohistochemical evaluation

Problems related to colonic anastomosis healing constitute the major morbidity in colorectal surgery. Patients without appropriate nutritional support are at higher risk of postsurgical complications, mainly due to reduced wound healing. Therefore, we investigated the effect of early and late postoperative total enteral nutrition (TEN) and glutamine addition on colon anastomosis healing using light microscopy and immunohistochemistry (IGF-I immunolabelling). In this study, 40 Wistar-albino rats underwent distal left colonic transection and anastomosis. The rats were then divided into four groups given different diets: delayed total enteral nutrition (dTEN; beginning 3 days postoperatively), delayed TEN with added glutamine (dTEN+Glutamine), early TEN (eTEN; beginning within 6h postoperatively), and early TEN with added glutamine (eTEN+Glutamine). Colon segments, including the anastomosis, were excised 7 days postoperatively and evaluated histopathologically for inflammation, mucosal healing, submucosal-muscular layer repair, the amounts of necrosis and vascularisation and immunohistochemically for IGF-I labelling. The inflammation and necrosis scores in the dTEN and dTEN+Glutamine groups were significantly greater than in the eTEN and eTEN+Glutamine groups. The IGF-I immunoreactivity increased in the eTEN, eTEN+Glutamine, and dTEN+Glutamine groups compared to dTEN (p<0.05). We concluded that early TEN and glutamine enrichment in the postoperative period improve anastomosis healing via IGF-I.

Expression of IGF-I, IGF-II, and IGF-IR in gallbladder carcinoma. A systematic analysis including primary and corresponding metastatic tumours

Aims: The insulin-like growth factor (IGF) system has been implicated in tumour development and progression. This study was designed to analyse the expression of the IGF-I receptor (IGF-IR) and its...

Immunohistochemical localization of components of the insulin-like growth factor system in human permanent teeth

There is growing evidence that the insulin-like growth factor (IGF) system plays an important role in the biology of oro-dento-facial tissues and organs, including the development, homeostasis and regeneration of the periodontium. To obtain basic data on the occurrence and distribution of IGF components in human permanent teeth we immunohistochemically investigated 25 extracted, decalcified and paraffin-embedded teeth using mono and polyclonal antibodies against the ligands IGF-I and -II, the IGF1 receptor (IGF1R) and all six IGF binding proteins (IGFBP-1 to -6). In the extracellular matrix (ECM) of the adhering periodontal ligament (PDL), immunoreactivity for IGF-I, -II and IGFBP-1 and -6 was observed. PDL fibroblasts showed immunostaining for the IGF1R. For the cementum, in the acellular cementum only IGF-II could be detected, while outer cementum layers with inserting Sharpey's fibers reacted with all antibodies applied except for IGFBP-4 and -6. In the pulp, mainly fibrotic areas and areas around denticles were immunoreactive for IGF-I, IGFBP-1, -3, -5 and -6. Predentin and odontoblastic processes were stained for IGF-I and IGFBP-3. The spatially oriented occurrence of components of the IGF system in human permanent teeth indicates that specific functions of the IGFs may be localized in particular tissue compartments. In the cementum, several IGF components were found indicating roles in tissue homeostasis or attachment. The PDL may function as a reservoir for IGFs probably bound to ECM components. PDL fibroblasts could then respond in a paracrine manner. In the pulp, the IGF system may be involved in odontoblast biology, fibrosis and denticle formation.

The IGF-I/IGF-I Receptor Pathway: Implications in the Pathophysiology of Thyroid Cancer

The biological actions of the insulin-like growth factor(IGF)-I are mediated by its activation of the IGF-I receptor (IGF-I R), a transmembrane tyrosine kinase linked to the Akt and ras-raf-MAPK cascades. A functional IGF-I R is required for the cell to progress through the cell cycle. Most importantly, cells lacking this receptor cannot be transformed by any of a number of dominant oncogenes, a finding that proves that the presence of the IGF-I R is important for the development of a malignant phenotype. Consistent with this role, it has been well established that IGF-I can protect cells from apoptosis under a variety of circumstances. For example, IGF-I prevents apoptosis induced by overexpression of c-myc in fibroblasts, by interleukin-3 withdrawal in interleukin-3-dependent hemopoietic cells, etoposide, a topoisomerase I inhibitor, anti-cancer drugs, UV-B irradiations, and serum deprivation. While the anti-apoptotic effect of IGF-I has been clearly demonstrated, the molecular mechanisms by which IGF-I inhibits apoptosis induced by these various stimuli remain unknown. We have previously documented increased IGF-I and IGF-I receptor immunoreactivity in human thyroid carcinomas with a corresponding up-regulation of IGF-I mRNA. Immunoreactivity for IGF-I and IGF-I receptor positively correlated with tumor diameter, but not with the occurrence of lymph node metastases. Several recent studies have identified new signaling pathways emanating from the IGF-I receptor that affect cancer cell proliferation, adhesion, migration and apoptosis, which represent critical functions for cancer cell survival and metastasizing capacity. In this review, various aspects of the IGF-I/IGF-I R pathway and its relationship to thyroid cancer are discussed.

Growth Hormone‐Releasing Peptide‐6 Increases Insulin‐Like Growth Factor‐I mRNA Levels and Activates Akt in RCA‐6 Cells as a Model of Neuropeptide Y Neurones

Chronic systemic administration of growth hormone (GH)-releasing peptide-6 (GHRP-6), an agonist for the ghrelin receptor, to normal adult rats increases insulin-like growth factor (IGF)-I mRNA and phosphorylated Akt (pAkt) levels in various brain regions, including the hypothalamus. Because neuropeptide Y (NPY) neurones of the arcuate nucleus express receptors for ghrelin, we investigated whether these neurones increase their IGF-I and p-Akt levels in response to this agonist. In control rats, immunoreactive pAkt was practically undetectable; however, GHRP-6 increased p-Akt immunoreactivity in the arcuate nucleus, with a subset of neurones also being immunoreactive for NPY. Immunoreactivity for IGF-I was detected in NPY neurones in both experimental groups. To determine if activation of this intracellular pathway is involved in modulation of NPY synthesis RCA-6 cells, an embryonic rat hypothalamic neuronal cell line that expresses NPY was used. We found that GHRP-6 stimulates NPY and IGF-I mRNA synthesis and activates Akt in this cell line. Furthermore, inhibition of Akt activation by LY294002 treatment did not inhibit GHRP-6 induction of NPY or IGF-I synthesis. These results suggest that some of the effects of GHRP-6 may involve stimulation of local IGF-I production and Akt activation in NPY neurones in the arcuate nucleus. However, GHRP-6 stimulation of NPY production does not involve this second messenger pathway.

Distinct expression pattern of insulin‐like growth factor family in rodent taste buds

The insulin-like growth factor (IGF) system is an important regulator of growth and differentiation in a variety of tissues. In the present study, the expression of IGF family members in the taste buds of mice and rats was examined. By reverse transcriptase polymerase chain reaction (RT-PCR) analysis, mRNA of IGF-I and -II, IGF-I receptor (IGF-IR), insulin receptor (insulin R), and IGF-binding protein (IGFBP)-2, -3, -4, -5, and -6 was detected in the taste bud-containing epithelium of the circumvallate papillae of mice. As suggested by the study using degenerate PCR (McLaughlin [2000] J. Neurosci. 20:5679-5688), IGF-IR was expressed in most of the taste bud cells of adult mice, as found by immunohistochemistry, and in those of postnatal day (P) 6 mice by in situ hybridization. Insulin R, which has strong homology to IGF-IR, was also detected in most of the taste bud cells of mice by immunohistochemistry and in situ hybridization. IGF-I immunoreactivity was detected in a few taste bud cells and in the epithelium surrounding taste buds. Northern blot analysis revealed that the amount of IGF-I mRNA in taste bud-containing epithelium was very low compared with that in liver. IGF-II immunoreactivity was weakly detected in mouse taste buds and the surrounding epithelium. In the rat tissue, a subset of the taste bud cells was positive for IGF-II. Among the six IGFBPs, IGFBP-2, -5, and -6 were detected in the mouse taste buds: IGFBP-2 and -5 immunoreactivity was seen in the majority of the taste bud cells, whereas IGFBP-6 immunoreactivity was found in the nerve fibers innervating the taste buds. In situ hybridization study also revealed that IGFBP-2 and -5 mRNA was synthesized in the taste buds of P6 mice and that the expression of these mRNAs overlapped in von Ebner's glands. These data reveal that IGF-I and -II might be produced in taste bud cells and (or) surrounding lingual epithelium and act through IGF-IR and insulin R locally in a paracrine and autocrine manner. The activity of these IGFs may be modulated through their interaction with IGFBP-2, -5, and 6.

Insulin-like growth factor I prevents corticosteroid-induced diaphragm muscle atrophy in emphysematous hamsters.

The aim of this study was to evaluate whether recombinant human insulin-like growth factor I (rhIGF-I) could attenuate or prevent diaphragm (DIA) fiber atrophy with corticosteroid (CS) administration to emphysematous (EMP) hamsters. DIA muscle IGF-I responses to CS administration with and without exogenous rhIGF-I administration were evaluated. Three groups were studied: 1) EMP; 2) EMP + triamcinolone (T; 0.4 mg.kg-1.day-1 im); and 3) EMP + T + IGF-I (600 microg/day by constant infusion). After 4 wk, the DIA was analyzed histochemically and biochemically (IGF-I mRNA levels by RT-PCR and endogenous and exogenous IGF-I peptide levels immunochemically). Body weights of EMP-T progressively decreased, while those of EMP and EMP-T-IGF-I remained stable despite similarly reduced food intake in both T groups. DIA weight was reduced with T but preserved with rhIGF-I infusion. DIA fiber proportions were similar among the groups. The cross-sectional areas of types I, IIa, and IIx fibers were reduced (17 to 31%) with T administration but unchanged with rhIGF-I infusion. DIA IGF-I mRNA levels were similar across all groups. By contrast, the endogenous DIA IGF-I levels were reduced (41%) in the EMP-T-IGF-I animals. Total DIA IGF-I levels (endogenous + exogenous) were still significantly reduced. IGF-I immunoreactivity confirmed this reduction in all DIA fibers. We conclude that DIA fiber atrophy with T was completely prevented by exogenous rhIGF-I administration. This effect was likely mediated by the pharmacological influences of exogenously administered rhIGF-I. We speculate that this results from increased bioavailability of free IGF-I to react with muscle receptors. Reduced endogenous IGF-I levels in the DIA likely reflect a negative-feedback influence. These results may have important clinical implications for treatment options to offset the adverse effects of CS on the respiratory muscles in patients with chronic lung disorders.

Localization of IGF-I, IGF-I receptor, and IGFBP-2 in developing Umbrina cirrosa (Pisces: Osteichthyes)

In this study, the distribution of IGF-I, IGF type I receptor (IGF-IR), and IGF-binding protein 2 (IGFBP-2) was investigated during larval and post-larval developmental stages of the shi drum ( Umbrina cirrosa) by immunohistochemistry using antisera raised against Sparus aurata IGF-I and IGF-IR, and against mouse IGFBP-2. Immunoreactivity of the mitogenic marker PCNA (proliferating cell nuclear antigen) was used for assessment of cellular proliferation. Distribution of IGF-I mRNA was studied by in situ hybridization. IGF-I immunoreactivity was detected in liver and developing intestine already in 1–5 day post-hatching larvae. From day 11, immunostaining in the intestine was evident in the enterocytes of the anterior intestine and in the apical zone of the epithelium of developing posterior intestine. Positive reaction with IGF-I antibody was also detected in chondrocytes, in the epithelium of the skin, gills and in the central nervous system (CNS), and lateral muscle. At hatching IGF-IR immunoreactivity was already detectable in developing CNS, notochord, and skin. From day 6 immunostaining was evident in the olfactory epithelium, in eyes and from day 11 in the developing olfactory bulbs and CNS. Positive reaction with IGF-IR antibody was also detected in chondrocytes, in the epithelium of the skin, gills, heart, and in the lateral muscle. Immunoreactive IGFBP-2, as detected by anti-mouse IGFBP-2 antiserum, exhibited generally a similar distribution pattern to that of IGF-I and IGF-IR. In situ hybridization, which has been performed by using riboprobes from S. aurata cDNA, revealed IGF-I mRNA in skeletal musculature, liver, and CNS. These data strongly suggest a role for the IGF system during development and growth of U. cirrosa.

Growth hormone receptor and insulin-like growth factor-I immunoreactivity in osteoclast-like cells during tooth eruption in the toothless (osteopetrotic) rat following treatment with colony-stimulating factor-1.

In the toothless (tl/tl) osteopetrotic rat, teeth form but fail to erupt. Treatment of tl/tl rats with colony-stimulating factor-1 (CSF-1) activates bone resorption by osteoclasts, permits tooth eruption, and up-regulates the immunoreactivity of bone marrow mononuclear cells to growth hormone receptor (GHr) and insulin-like growth factor (IGF)-I. This study examined the distribution of tartrate-resistant acid phosphatase (TRAP) and immunoreactivity for GHr and IGF-I in osteoclast-like cells located on the alveolar bone margin, adjacent to the lower first molar crown, in 14-day-old normal and tl/tl rats, following treatment with CSF-1. Osteoclast-like cells demonstrated a positive reaction for TRAP, GHr, and IGF-I in all groups. However, in tl/tl tissue, osteoclast-like cells were generally negative for GHr. There was no significant difference in the total number of TRAP-, GHr-, and IGF-I-positive osteoclast-like cells on the adjacent bone margin in normal, normal treated with CSF-1, and tl/tl rats. CSF-1 treatment of the tl/tl rat significantly increased the total number of osteoclast-like cells, which were positive for TRAP (p < 0.001), GHr (p < 0.05) and IGF-I (p < 0.01).

Expression of insulin-like growth factor family in the rat olfactory epithelium.

The goal of this study was to determine the cellular sites of insulin-like growth factor (IGF) family expression in the rat olfactory epithelium. By RT-PCR analysis, mRNAs of IGF-I, II, IGF-I receptor (IGF-IR), and IGF binding proteins (IGFBPs) 2, 3, 4, 5, and 6 were found to be expressed in the olfactory mucosa. Immunoreactivity for IGF-IR was restricted to a subset of olfactory receptor cells whose cell bodies were situated in the basal region of the olfactory epithelium. Intense IGF-I immunoreactivity was detected in the supporting cells, whereas IGF-II immunoreactivity was observed in the lamina propria, but not in the epithelium. Immunoreactivities for IGFBP-2, IGFBP-3, and IGFBP-6 were detected in olfactory receptor cells. In addition, axon bundles in the lamina propria displayed an intense reaction for IGFBP-6. IGFBP-4 immunoreactivity was restricted to the apex of the olfactory epithelium. Intense IGFBP-5 immunoreactivity was observed in Bowman's glands. These results suggest that IGF-I is secreted from supporting cells and affects its receptor- expressing olfactory cells. IGFBPs may modulate IGF-I activity via their production by Bowman's glands, olfactory cells, and supporting cells themselves.

IGF-I in human breast cancer: low differentiation stage is associated with decreased IGF-I content.

Few investigations on the potential role of IGF-I in human breast cancer have used morphological criteria, and the data presented on the localisation of IGF-I are controversial. Moreover, little information exists on a potential correlation between local IGF-I and the grade of malignancy or prognostic factors. Therefore, we investigated the immunohistochemical localisation of IGF-I in specimens of human breast cancer tumours of the ductal type, graded as G1/G2 (well-/moderately differentiated, n=115) and G3 (poorly differentiated, n=28). IGF-I immunoreactivity was quantified using a scaling from no (-) to numerous (+++) IGF-I-immunoreactive cells. From 29 of the G1/G2 and 17 of the G3 tumours IGF-I was also measured by RIA. Cytosolic oestrogen receptor (ER) and progesterone receptor (PR) levels, and S-phase fraction were established and related to the number of IGF-I-immunoreactive cells. IGF-I immunoreactivity occurred predominantly in ductal epithelial cells. Of G3 tumours, 57% exhibited IGF-I immunoreactivity as compared with 84% of G1/G2 tumours. Correspondingly, the amount of IGF-I measured by RIA was significantly lower in G3 tumours (6.9+/-0.9 ng/g wet weight) than in G1/G2 tumours (10.5+/-1.1 ng/g wet weight) (P=0.031). G1/G2 tumours exhibited a higher percentage of IGF-I-immunoreactive cells (16% -, 23% +, 41% ++, 20% +++) than G3 tumours (43% -, 37% +, 12% ++, 8% +++). When comparing the - with the +++ G1/G2 tumours, the frequency of IGF-I-immunoreactive cells was related significantly to the ER (P<0.016) and the PR (P<0.008) levels. In G1/G2 and G3 tumours, the ER and PR levels increased with the amount of IGF immunoreactivity while the S-phase fraction increased with decreasing IGF-I content. In 25% of the specimens, IGF-I immunoreactivity occurred in stromal cells, but there was no obvious difference between the different types of tumours. The survival of the G1/G2 tumour patients increased with increasing numbers of IGF-I-immunoreactive cells. It is concluded that IGF-I is associated with the more-differentiated type of epithelial cells and that increasing dedifferentiation goes along with decreased IGF-I content. Thus, the presence of IGF-I immunoreactivity in breast cancer epithelial cells indicates a lower degree of malignancy than the lack of IGF-I.

Tissue distribution of components of the insulin-like growth factor system in sudden infant death and controls

Growth factors may be involved in sudden infant death (SID). Among these factors, the insulin-like growth factor (IGF) family is important in human fetal and perinatal organ growth and development. In order to detect probable differences in the occurrence and distribution of components of the IGF system, tissue samples from liver, lung, skin, parotid and thyroid gland, gut and cerebellum from SID children ( n=9) and controls ( n=6) aged between 14 and 258 days of life (mean 105 days) were stained immunohistochemically using antibodies against IGF-I, IGF-II and their specific IGF-I-receptor (IGF-IR). In contrast to controls in hepatocytes of SID children a reduction or an absence of immunoreactivity for IGF-I and IGF-IR and a weaker staining for IGF-II was detected. IGF-II in smooth muscle layers in the gut and IGF-I in epithelial cells in intestinal specimens also showed a reduced immunoreactivity in SID children and those who died traumatic deaths. In the other organs examined no significant differences in the distribution of the insulin-like growth factor system between the groups could be detected, indicating that in SID children no fundamental differences or alterations in the physiology of the IGF system occur. Because of the decreased immunostaining of IGFs in the liver and intestine of SID cases, a local dysregulation may be discussed.

Increased expression of insulin-like growth factor I in skin in amyotrophic lateral sclerosis

OBJECTIVESInsulin-like growth factor I (IGF-I) has potent effects on motor neuron survival and is being studied as a possible therapeutic agent for ALS. However, little is known concerning IGF-I in...

Expression of mRNA encoding IGF-I, IGF-II and type 1 IGF receptor in bovine ovarian follicles.

IGFs regulate gonadotrophin-stimulated proliferation and differentiation of granulosa and theca cells in vitro. However, the detailed pattern of mRNA expression of IGFs in bovine follicles remains controversial. The objectives of this study were therefore to describe the temporal and spatial pattern of expression of mRNA encoding IGF-I, IGF-II and the type 1 IGF receptor in bovine follicles in vivo. The expression of mRNA encoding IGF-II was detected in theca tissue from around the time of antrum formation up to and during the development of dominance. No IGF-II mRNA expression was detected in granulosa cells. In the majority of follicles we were unable to detect mRNA encoding IGF-I in either granulosa or theca tissue from follicles at any stage of development. Occasionally low amounts of mRNA encoding IGF-I were detected in the theca externa and connective tissue surrounding some follicles. Type 1 IGF receptor mRNA was detected in both granulosa and theca cells of preantral and antral follicles. Expression was greater in granulosa tissue compared with theca tissue. We also measured IGF-I and -II mRNA in total RNA isolated from cultured granulosa and theca cells using reverse transcriptase PCR. In contrast to the in vivo results, IGF-II mRNA was detected in both granulosa and theca tissue. IGF-I mRNA was detected in theca tissue and in very low amounts in granulosa cells. Using a specific IGF-I RIA we were unable to detect IGF-I immunoreactivity in granulosa conditioned cell culture media. Using immunohistochemistry we detected IGF-I immunoreactivity in some blood vessels within the ovarian stroma. We conclude from these results that IGF-II is the principal intrafollicular IGF ligand regulating the growth of bovine antral follicles. In preantral follicles the expression of mRNA encoding type 1 IGF receptor but absence of endogenous IGF-I or -II mRNA expression, highlights a probable endocrine mechanism for the IGF regulation of preantral follicle growth.