Biphasic concentration dependency of stimulation of myoblast differentiation by somatomedins

1986 ◽  
Vol 250 (5) ◽  
pp. C771-C778 ◽  
Author(s):  
J. R. Florini ◽  
D. Z. Ewton ◽  
S. L. Falen ◽  
J. J. Van Wyk
Keyword(s):  
Growth Factor ◽  
Myoblast Differentiation ◽  
Medium Components ◽  
Low Concentrations ◽  
Concentration Dependency ◽  
Epidermal Growth ◽  
L6 Myoblast ◽  
Stimulation Of ◽  
Insulin Like Growth Factors

It is widely believed that mitogens inhibit in vitro differentiation of myoblasts to form postmitotic myotubes, but we and others have shown that the mitogenic hormones insulin and the insulin-like growth factors (IGFs) stimulate myoblast differentiation. We now report the results of concentration-dependency studies that resolve this disagreement. We found that the IGFs give a biphasic dose-response curve; at low concentrations, there is progressive stimulation of L6 myoblast differentiation; at higher concentrations, there is a progressive decrease. Similar results were obtained with IGF-II and insulin. When differentiation was maximally stimulated (by 1,280 ng/ml insulin), adding rat IGF-II gave decreases in differentiation similar to those reported for other mitogens. Two trivial explanations have been eliminated: stimulation of differentiation (at low concentrations) is not due to enhanced survival or growth of the cells, and inhibition (at higher concentrations) is not a toxic effect. In L6 cells, epidermal growth factor and fibroblast growth factor had no effect on proliferation or differentiation. We conclude that the effects of medium components on myoblast differentiation cannot be generalized to indicate inhibition by all mitogens; depending on the cell lines and concentrations used, certain mitogens may either stimulate or inhibit differentiation.

scholarly journals Lack of correlation between changes in polyphosphoinositide levels and actin/gelsolin complexes in A431 cells treated with epidermal growth factor.

1991 ◽  
Vol 112 (6) ◽  
pp. 1151-1156 ◽  
Author(s):  
C Y Dadabay ◽  
E Patton ◽  
J A Cooper ◽  
L J Pike
Keyword(s):  
Growth Factor ◽  
Actin Cytoskeleton ◽  
Actin Polymerization ◽  
Inositol Phosphates ◽  
A431 Cells ◽  
Pi Turnover ◽  
Epidermal Growth ◽  
Stimulation Of

The polyphosphoinositides, PIP and PIP2, have been proposed to regulate actin polymerization in vivo because they dissociate actin/gelsolin complexes in vitro. We tested this hypothesis by comparing the ability of EGF and bradykinin to affect PI metabolism and the actin cytoskeleton in A431 cells. EGF, but not bradykinin, was found to induce ruffling and dissociation of actin/gelsolin complexes in these cells. However, both EGF and bradykinin stimulated the accumulation of inositol phosphates in [3H]inositol-labeled cells indicating that stimulation of PI turnover is not sufficient for the induction of changes in actin/gelsolin complex levels. EGF stimulated a twofold increase in the level of PIP in A431 cells. Other phosphoinositide levels were not markedly altered. Treatment of the cells with cholera toxin abrogated the EGF-induced rise in PIP levels without altering the dissociation of actin from gelsolin. These data indicate that increases in PIP and/or PIP2 are not necessary for dissociation of actin/gelsolin complexes. Overall, these experiments suggest that in A431 cells, the effects of EGF on the actin cytoskeleton are unlikely to be mediated through changes in PIP or PIP2 levels.

Effect of epidermal growth factor on secondary palatal epithelium in vitro: tissue isolation and recombination studies

Development ◽  
1980 ◽  
Vol 58 (1) ◽  
pp. 93-106
Author(s):  
Mary S. Tyler ◽  
Robert M. Pratt
Keyword(s):  
Cell Death ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Programmed Cell Death ◽  
Dna Synthesis ◽  
Thymidine Incorporation ◽  
Control Medium ◽  
Epidermal Growth ◽  
Stimulation Of

Previous studies have shown that epidermal growth factor (EGF), a peptide of m.w. 6045, can specifically inhibit in organ culture the cessation of DNA synthesis and programmed cell death that normally occur in the presumptive fusion zone (PFZ) of the secondary palatal epithelium. The aim of this study was to determine if EGF acts directly on the epithelium to exert its effect and if there is a requirement for the underlying mesenchyme. Palatal processes from 13- and 14-day Swiss Webster embryonic mice were enzymatically separated into epithelium and mesenchyme which were then cultured alone or in transfilter recombination for up to 72 h. Tissues were examined by transmission- and scanning-electron microscopy and DNA synthesis was monitored autoradiographically using [3H]thymidine incorporation. In isolated epithelium cultured in control medium, cell death occurred in the PFZ and DNA synthesis did not occur in the oral and nasal epithelial regions. EGF (20–50 ng/ml) did not prevent cell death in the PFZ and failed to stimulate DNA synthesis in the isolated epithelium; EGF, however, did have an effect on epithelial cell morphology. In the presence of mesenchyme and EGF, there was extensive proliferation in the entire epithelium and cell death within the PFZ was not evident. The results indicate that the stimulation of DNA synthesis in the palatal epithelium by EGF requires the presence of the underlying mesenchyme and that EFG alone is not sufficient to inhibit programmed cell death within the PFZ of the isolated palatal epithelium.

scholarly journals Epidermal Growth Factor Family Members: Endogenous Mediators of the Ovulatory Response

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 77-84 ◽  
Author(s):  
H. Ashkenazi ◽  
X. Cao ◽  
S. Motola ◽  
M. Popliker ◽  
M. Conti ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Oocyte Maturation ◽  
Egf Receptor ◽  
Kinase Inhibitor ◽  
Meiotic Maturation ◽  
Expression Of Genes ◽  
Epidermal Growth ◽  
Stimulation Of

Previous studies showed that epidermal growth factor (EGF) and TGFα mimic the action of LH on the resumption of oocyte maturation. We tested whether EGF-like agents, such as amphiregulin (AR), epiregulin (ER), and betacellulin (BTC), also mediate the LH stimulation of the ovulatory response in the rat. LH induced transient follicular expression of AR, ER, and BTC mRNA, reaching a maximum after 3-h incubation. Furthermore, the addition of ER, AR, and BTC to the culture medium could mimic some of LH actions. AR and ER fully simulated LH-induced resumption of meiosis in vitro, whereas BTC was less effective. To study the putative involvement of EGF-like factors in mediation of LH signal, the effect of the EGF receptor kinase inhibitor AG1478 was tested. When added with LH, AG1478, but not its inactive analog AG43, reduced EGF receptor phosphorylation and oocyte maturation compared with follicles treated with LH only. In addition to the inhibition of resumption of meiosis, AG1478 administration into the bursa (3 μg/bursa) resulted in 51% (P < 0.0005) inhibition of ovulation in the treated ovaries, compared with the untreated contralateral ones, as well as to the vehicle-treated ovaries (P < 0.02). LH, as well as ER, induced the expression of genes associated with the ovulatory response like rat hyaluronan synthase-2, cycloxygenase-2, and TNFα-stimulated gene 6 mRNA, whereas AG1478 inhibited this effect of LH. Release of EGF-like factors from the membrane is dependent on activated metalloproteases. Indeed, Galardin, a broad-spectrum metalloprotease inhibitor, but not a specific matrix metalloprotease 2 and 9 inhibitor, suppressed meiotic maturation induced by LH. Conversely, meiotic maturation induced by ER was not affected by Galardin, thus, supporting the notion that LH releases follicular membrane-bound EGF-like agents. In summary, EGF-like factors such as ER, AR, and BTC seem to mediate, at least partially, the LH stimulation of oocyte maturation, ovulatory enzyme expression, and ovulation.

Vasopressin stimulation of cell proliferation in the rat pituitary gland in vitro

1990 ◽  
Vol 126 (2) ◽  
pp. 255-259 ◽  
Author(s):  
A. M. McNicol ◽  
J. E. Murray ◽  
W. McMeekin
Keyword(s):  
Growth Factor ◽  
Test System ◽  
Pituitary Cells ◽  
Short Term ◽  
Corticotrophin Releasing Factor ◽  
Rat Pituitary ◽  
Epidermal Growth ◽  
Short Term Culture ◽  
Stimulation Of

ABSTRACT Proliferative activity was measured in rat anterior pituitary cells in short-term culture by calculating the labelling index (LI), based on the immunohistochemical detection of cells incorporating the thymidine analogue bromodeoxyuridine. Basal LI was reproducible in the test system. Arginine vasopressin (AVP) induced a dose-related increase in LI up to 20 ng/ml. Corticotrophin-releasing factor-41 (CRF-41) had no effect at doses up to 20 ng/ml. However, in the presence of 10 ng CRF-41/ml, AVP induced a greater increase in LI at lower doses than did AVP alone. Fibroblast growth factor also induced a significant increase in LI. In the system used, epidermal growth factor and insulin had no effect on proliferation. Journal of Endocrinology (1990) 126, 255–259

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