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Introduction Insulin-like growth factors I and II (IGF-I and -II) are polypeptides with structural homology to proinsulin and are important in regulating fetal and placental growth ( DeChiara et al. 1990 , Liu et al. 1993
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Introduction Various complications during pregnancy can impact the health and survival of a fetus, among the most significant of these being intrauterine growth restriction (IUGR). IUGR affects upwards to 8% of human pregnancies, and occurs
The Diabetes Institute, Ohio University, Athens, Ohio, USA
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Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Biomedicine, Aarhus University, Aarhus, Denmark
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Medical Research Laboratory, Aarhus University, Aarhus, Denmark
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The Diabetes Institute, Ohio University, Athens, Ohio, USA
Edison Biotechnology Institute, Ohio University, Athens, Ohio, USA
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Introduction Although growth hormone (GH) has been primarily studied for its effects on linear growth, pronounced stimulation of lipolysis was among the first metabolic effects reported in human subjects following the introduction of pituitary
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The hepatocyte growth factor (HGF) system HGF is an 87 kDa growth factor first identified and characterized due to its angiogenic and proliferative effects in primary epithelial cell cultures ( Bussolino et al . 1992 ). This pioneered a number of
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Abstract
Cation-exchange chromatography effectively concentrates the cell growth activity present in whey and we have used this process as a basis to characterise further the growth factors present in bovine milk. Under neutral conditions, total bioactivity in the growth factor-enriched cation-exchange fraction chromatographed with an apparent molecular mass of 80–100 kDa. In contrast, acid gelfiltration chromatography resolved two peaks of cell growth activity. A peak at 15–25 kDa contained the bulk of growth activity for Balb/c 3T3 fibroblasts while bioactivity for L6 myoblasts and skin fibroblasts eluted with a molecular mass of 6 kDa. A peak of inhibitory activity for Mv1Lu and MDCK cells also eluted at 15–25 kDa. Both IGF-I and IGF-II were purified from fractions that eluted at 6 kDa, although the IGF peptides alone did not account for the total bioactivity recovered. Platelet-derived growth factor (PDGF), identified by radioreceptor assay, eluted at a slightly higher molecular mass than the peak of growth activity for Balb/c 3T3 cells, and an anti-PDGF antibody was without effect on the growth of Balb/c 3T3 cells in response to the whey-derived factors. Further purification of the inhibitory activity for epithelial cells yielded a sequence for transforming growth factor β (TGF-β), and all inhibitory activity for Mv1Lu cells was immuno-neutralised by an antibody against TGF-β. In contrast, this antibody decreased the growth of Balb/c 3T3 fibroblasts in the whey-derived extract by only 10%. Finally, a cocktail of recombinant growth factors containing IGF-I, IGF-II, PDGF, TGF-β and fibroblast growth factor 2 stimulated growth of Balb/c 3T3 cells to a level equivalent to only 51% of that observed in the milk-derived growth factor preparation. We conclude that: (i) cell growth activity recovered from bovine whey is present in acid-labile high molecular weight complexes; (ii) all cell growth inhibitory activity for epithelial cells can be accounted for by TGF-β; (iii) IGF-I and IGF-II co-elute with the major peak of activity for L6 myoblasts and skin fibroblasts, although the IGF peptides alone do not explain the growth of these cells in the whey-derived extract; and (iv) neither PDGF nor TGF-β account for the 15–25 kDa peak of Balb/c 3T3 growth activity. These data suggest the presence of additional mitogenic factors in bovine milk.
Journal of Endocrinology (1997) 154, 45–55
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molecules that are involved in this early embryo–uterine interaction. In this study, we review the data on the functional role of major hormones, cytokines, and growth factors during implantation process. Due to space limitation and previously published
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Introduction Hormonal disturbance, in either secretion amount or function, often occurs in parallel with impairment of glucose/lipid/protein metabolism in obesity. Two pivotal hormones, insulin and growth hormone (GH), which synergistically
Department of Surgery, Centre for Pancreatic Diseases, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
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Department of Surgery, Centre for Pancreatic Diseases, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
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Department of Surgery, Centre for Pancreatic Diseases, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
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Department of Surgery, Centre for Pancreatic Diseases, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
Department of Surgery, Centre for Pancreatic Diseases, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
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). Accordingly, interest has been directed toward factors identified as critical to pancreatic organogenesis. To this end, we have implicated transforming growth factor β (TGFβ) in the control of human islet plasticity ( Hanley & Rosenberg 2007 ). Likewise
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Introduction Insulin-like growth factor 1 (IGF-1) is a critical fetal growth hormone. Fetal and umbilical cord concentrations of IGF-1 have a strong, positive correlation with birth weight ( Gluckman et al. 1983 , Lassarre et al. 1991
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Novel growth factors have often been given names which relate to their original site of discovery or their first known target cell or biological action. Subsequent studies have frequently shown such nomenclature to be misleading as more is learned about the factor concerned. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) which in fact act as mitogens for a great variety of cell types and transforming growth factor-β (TGFβ) which is better recognized as a growth inhibitor are all typical examples. Moreover, in addition to their growth regulatory roles, peptide growth factors also serve to modulate cell differentiation and function. The recently characterized hepatocyte growth factor (HGF) joins this illustrious family of cytokines which have proven rather more versatile than their original descriptive title suggests.
Characterization
Hepatocyte growth factor was originally identified and characterized by three independent experimental approaches.
(a) Michalopoulos described a mitogenic activity in the serum of
