Stimulation of intestinal epithelial cell proliferation in culture by growth factors in human and ruminant mammary secretions

1987 ◽  
Vol 113 (2) ◽  
pp. 285-290 ◽  
Author(s):  
A. N. Corps ◽  
K. D. Brown

ABSTRACT Samples of human and ruminant mammary secretions stimulated the proliferation of rat intestinal epithelial (RIE-1) cells in culture. The stimulation was dose-dependent, and samples taken prepartum had greater potency than those taken after parturition. When various hormones and growth factors known to be present in milk were tested, only epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I) stimulated the proliferation of RIE-1 cells. IGF-I was effective at lower concentrations than insulin, and the maximal stimulation induced by each of these two polypeptides was greater than that induced by EGF. The maximal stimulation induced by samples of mammary secretions was similar to that induced by insulin or IGF-I. J. Endocr. (1987) 113, 285–290

1996 ◽  
Vol 16 (3) ◽  
pp. 249-263 ◽  
Author(s):  
Hai-Lan Chen ◽  
Philip S. Rudland ◽  
John A. Smith ◽  
David G. Fernig

Maximal stimulation of DNA synthesis in quiescent rat mammary (Rama) 27 fibroblasts is elicited by epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) 18 h after the initial addition of the growth factors-the ‘lag’ period. At maximally-stimulating concentrations, EGF and bFGF are interchangeable 9 h after their initial addition. When the initial concentration of growth factor is below that required to elicit a maximal response, it is possible to increase the level of DNA synthesis by increasing the concentration of growth factor 9 h after its initial addition. When the initial concentration of growth factor is high, substitution by a lower concentration of growth factor after 9 h allows a greater proportion of cells to synthesize DNA than would be expected from a continuous low dose of growth factor. Similar results are obtained when both the growth factor and its concentration are changed 9 h after the initial addition of growth factor. However, when EGF at a low concentration is substituted for a high concentration of EGF or bFGF the resulting increase in the levels of DNA synthesis is greater when EGF rather than bFGF is added for a second time. The half-life of the growth-stimulatory signals delivered by EGF and by bFGF 9 h after their initial addition is 1–2 h. These results suggest that to stimulate DNA synthesis: (i) EGF or bFGF must deliver a signal(s) continuously; (ii) the initial signals produced by EGF and bFGF are equivalent; (iii) the signals produced between 9–18 h by EGF may be different to those produced by bFGF.


1991 ◽  
Vol 128 (3) ◽  
pp. 389-393 ◽  
Author(s):  
B. Houston ◽  
I. E. O'Neill

ABSTRACT Cultured chicken hepatocytes were used to investigate whether insulin and GH interact to regulate insulin-like growth factor-I (IGF-I) production in vitro. In the first set of experiments hepatocytes were preincubated for 6 h in hormone-free medium, and the effects of various combinations of insulin and GH on IGF-I production over the next 24 h were quantified by radioimmunoassay. Basal IGF-I production was 5·36 pg IGF-I/μg DNA and this was increased 1·31±0·13-fold (mean ± s.e.m.) by insulin, 1·90±0·24-fold by GH and 4·46±0·68-fold by a combination of insulin and GH. These results demonstrate that insulin and GH interact synergistically to stimulate IGF-I production in vitro. The synergism with GH occurred at physiological concentrations of insulin with half-maximal stimulation occurring at an insulin concentration of 6 ng/ml. In hepatocytes which had been exposed to insulin immediately before the start of the experiment, the presence of insulin was no longer required for maximal stimulation of IGF-I production by GH. This in-vitro system will facilitate the study of the molecular basis of the interaction between insulin and GH. Journal of Endocrinology (1991) 128, 389–393


1988 ◽  
Vol 116 (1) ◽  
pp. 97-100 ◽  
Author(s):  
D. Schams ◽  
R. Koll ◽  
C. H. Li

ABSTRACT The effect of insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), fibroblast growth factor (FGF) and nerve growth factor (NGF) on production of oxytocin and progesterone by cultured bovine granulosa and luteal cells was studied. Secretion of oxytocin was stimulated, in a dose-dependent manner, by IGF-I at 48 and 120 h of culture to levels much higher than those after stimulation with LH, FSH, EGF, FGF or NGF. A similar effect of IGF-I was observed for progesterone but, in contrast to oxytocin, secretion of progesterone was not increased by EGF, NGF or FGF. During primary culture, for 4 h, of dispersed bovine luteal cells obtained from corpora lutea between days 4 and 10 of the oestrous cycle, all the growth factors tested failed to stimulate secretion of oxytocin or progesterone. The data suggest the relevance of growth factors (especially IGF-I) for ovarian physiology and their possible importance for differentiation of follicles and luteinization. J. Endocr. (1988) 116, 97–100


1989 ◽  
Vol 71 (4) ◽  
pp. 538-544 ◽  
Author(s):  
Masaki Kurihara ◽  
Yoshiharu Tokunaga ◽  
Keisuke Tsutsumi ◽  
Tsutomu Kawaguchi ◽  
Kazuto Shigematsu ◽  
...  

✓ Receptors for insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) were localized and characterized in eight samples of human meningioma (four fibrous, two meningothelial, and two angioblastic types), using quantitative autoradiographic techniques. Effects of both growth factors on deoxyribonucleic acid (DNA) synthesis in the cultured meningioma cells were examined. High numbers of specific binding sites for both IGF-I and EGF were homogeneously present in tissue sections derived from fibrous and meningothelial types of meningiomas, whereas binding sites for these growth factors were not detectable in adjacent leptomeninges. While relatively large numbers of IGF-I binding sites were located in the wall of the intratumoral vasculature, the number of binding sites in the stromal component was lower in angioblastic-type meningiomas, including a low number of EGF binding sites detected only in the stromal portion. Scatchard analysis revealed the presence of a single class of high-affinity binding sites for both IGF-I and EGF in the meningiomas examined (dissociation constant (Kd) = 0.6 to 2.9 nM, and the maximum number of binding sites (Bmax) = 16 to 80 fmol/mg for IGF-I; and Kd = 0.6 to 4.0 nM, Bmax = 3 to 39 fmol/mg for EGF). Both growth factors increased the synthesis of DNA, in a dose-dependent manner, as measured by 3H-thymidine incorporation. The combination of IGF-I and EGF synergistically stimulated the synthesis of DNA, and the effects seen with 10% fetal bovine serum could be reproduced at a concentration of 10−10 M. These observations can be interpreted to mean that both IGF-I and EGF may be involved in the growth modulation of meningiomas, possibly through paracrine or autocrine mechanisms.


Development ◽  
1990 ◽  
Vol 110 (1) ◽  
pp. 221-227
Author(s):  
A.N. Corps ◽  
D.R. Brigstock ◽  
C.J. Littlewood ◽  
K.D. Brown

125I-labelled epidermal growth factor (125I-EGF) and 125I-labelled insulin-like growth factor-I (125I-IGF-I) bound to trophoderm cells from pig blastocysts obtained on days 15–19 of pregnancy. Specific binding was detected on freshly isolated cell suspensions and on cells cultured for several days. The binding of 125I-EGF was inhibited by increasing concentrations of EGF, but not by various other growth factors and hormones. Chemical cross-linking of 125I-EGF to its receptors using disuccinimidyl suberate (DSS) revealed a radiolabelled band of relative molecular mass 160,000, similar to that identified as the EGF receptor in other cell types. The binding of 125I-IGF-I was inhibited by both IGF-I and insulin, indicating that the receptors were either type I IGF receptors or insulin receptors. Cross-linking of 125I-IGF-I to serum-free supernatants from trophoderm cultures showed that the cells secreted an IGF-binding protein, giving a complex of relative molecular mass about 45,000. The presence of receptors for EGF and IGF/insulin suggests that these factors could be involved in regulating the growth and development of the early blastocyst.


Author(s):  
Rémi Quirion ◽  
Dalia M. Araujo ◽  
Paul A. Lapchak ◽  
David Seto ◽  
Jean-Guy Chabot

ABSTRACT:It is well known that various markers of the cholinergic synapse are altered in Alzheimer's Disease. Much interest is currently focussing on the evaluation of the possible efficacy of certain growth factors, especially nerve growth factor (NGF), to reduce or reverse cholinergic neuronal losses. Here we report that other growth factors (epidermal growth factor and insulin-like growth factor I) and a lymphokine, interleukin-2, are able to block acetylcholine release in the rat hippocampus. This suggests that while certain growth factors like NGF may have positive effects on the cholinergic neuron, others may act as “negative” factors on this neuronal population.


2010 ◽  
Vol 299 (1) ◽  
pp. R33-R41 ◽  
Author(s):  
L. Bouraoui ◽  
E. Capilla ◽  
J. Gutiérrez ◽  
I. Navarro

Primary cultures of rainbow trout ( Oncorhynchus mykiss ) adipocytes were used to examine the main signaling pathways of insulin and insulin-like growth factor I (IGF-I) during adipogenesis. We first determined the presence of IGF-I receptors (IGF-IR) and insulin receptors (IR) in trout preadipocytes ( day 5) and adipocytes ( day 14). IGF-IRs were more abundant and appeared to be in higher levels in differentiated cells than in preadipocytes, whereas IRs were detected in lower but constant levels throughout the culture. The cells were immunoreactive against ERK1/2 MAPK, and AKT/PI3K, components of the two main signal transduction pathways for insulin and IGF-I receptors. Stimulation of MAPK phosphorylation by IGF-I was higher in preadipocytes than in adipocytes, while no effects were observed in MAPK phosphorylation after incubation of cells with insulin. AKT phosphorylation increased in the presence of both insulin and IGF-I, with higher levels of stimulation in adipocytes than in preadipocytes. Activation of both pathways was blocked by the use of specific inhibitors of MAPK (PD98059) and AKT (wortmannin). We describe here, for the first time, the effects of IGF-I and insulin on 2-deoxyglucose uptake in primary culture of trout adipocytes. IGF-I was more potent in stimulating glucose uptake than insulin, and PD98059 and wortmannin inhibited the stimulation of glucose uptake by this growth factor, suggesting that IGF-I plays an important metabolic role in trout adipocytes. Our results suggest that differential activation of the MAPK and AKT pathways are involved in the IGF-I- and insulin-induced effects of trout adipocytes during the various stages of adipogenesis.


Development ◽  
1990 ◽  
Vol 108 (3) ◽  
pp. 491-495
Author(s):  
R. Spaventi ◽  
M. Antica ◽  
K. Pavelic

Growth factors have an important role in the regulation of cell growth, division and differentiation. They are also involved in the regulation of embryonic growth and differentiation. Insulin and insulin-like growth factor I (IGF I) play an important part in these events in the later stages of embryogenesis, when organogenesis is completed. In this study, we are presenting evidence that insulin and IGF I are also secreted by embryonic tissues during the prepancreatic stage of mouse development. We found measurable amounts of insulin and IGF I in 8- to 12-day-old mouse embryos. We also showed that embryonic cells derived from 8-, 9- and 10-day-old mouse embryos secrete insulin, IGF I and/or related molecules. Furthermore, the same growth factors, when added to the culture of 9-day-old mouse embryonic cells, stimulate their proliferation. These results lead to the conclusion that insulin can stimulate the growth of embryonic cells during the period when pancreas is not yet formed, which is indirect evidence for a paracrine (or autocrine) type of action.


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