scholarly journals The Somatomedin Hypothesis: 2001

2001 ◽  
Vol 22 (1) ◽  
pp. 53-74 ◽  
Author(s):  
Derek Le Roith ◽  
Carolyn Bondy ◽  
Shoshana Yakar ◽  
Jun-Li Liu ◽  
Andrew Butler
Keyword(s):  
Growth And Development ◽  
Gene Deletion ◽  
Somatic Growth ◽  
Postnatal Growth ◽  
Protein Levels ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein

Abstract Since the original somatomedin hypothesis was conceived, a number of important discoveries have allowed investigators to modify the concept. Originally somatic growth was thought to be controlled by pituitary GH and mediated by circulating insulin-like growth factor-I (IGF-I, somatomedin C) expressed exclusively by the liver. With the discovery that IGF-I is produced by most, if not all, tissues, the role of autocrine/paracrine IGF-I vs. the circulating form has been hotly debated. Recent experiments using transgenic and gene-deletion technologies have attempted to answer these questions. In the liver-specific igf-1 gene-deleted mouse model, postnatal growth and development are normal despite the marked reduction in circulating IGF-I and IGF-binding protein levels; free IGF-I levels are normal. Thus, the normal postnatal growth and development in these animals may be due to normal free IGF-I levels (from as yet unidentified sources), although the role of autocrine/paracrine IGF-I has yet to be determined.

scholarly journals Steroid Receptor Coactivator 3 Maintains Circulating Insulin-Like Growth Factor I (IGF-I) by Controlling IGF-Binding Protein 3 Expression

2008 ◽  
Vol 28 (7) ◽  
pp. 2460-2469 ◽  
Author(s):  
Lan Liao ◽  
Xian Chen ◽  
Shu Wang ◽  
Albert F. Parlow ◽  
Jianming Xu
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Steroid Receptor Coactivator ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

ABSTRACT Steroid receptor coactivator 3 (SRC-3/AIB1/ACTR/NCoA-3) is a transcriptional coactivator for nuclear receptors including vitamin D receptor (VDR). Growth hormone (GH) regulates insulin-like growth factor I (IGF-I) expression, and IGF-I forms complexes with acid-labile subunit (ALS) and IGF-binding protein 3 (IGFBP-3) to maintain its circulating concentration and endocrine function. This study demonstrated that the circulating IGF-I was significantly reduced in SRC-3−/− mice with the C57BL/6J background. However, SRC-3 deficiency affected neither GH nor ALS expression. The low IGF-I level in SRC-3−/− mice was not due to the failure of IGF-I mRNA and protein synthesis but was a consequence of rapid degradation. The rapid IGF-I degradation was associated with drastically reduced IGFBP-3 levels. Because IGF-I and IGFBP-3 stabilize each other, SRC-3−/− mice were crossbred with the liver-specific transthyretin (TTR)-IGF-I transgenic mice to assess the relationship between reduced IGF-I and IGFBP-3. In SRC-3−/−/TTR-IGF-I mice, the IGF-I level was significantly increased over that in SRC-3−/− mice, but the IGFBP-3 level failed to increase proportionally, indicating that the low IGFBP-3 level is a responsible factor that limits the IGF-I level in SRC-3−/− mice. Furthermore, IGFBP-3 mRNA was reduced in SRC-3−/− mice. The IGFBP-3 promoter activity induced by vitamin D, through VDR, was diminished in SRC-3−/− cells, suggesting an important role of SRC-3 in VDR-mediated transactivation of the IGFBP-3 gene. In agreement with the role of SRC-3 in VDR function, the expression of several VDR target genes was also reduced in SRC-3−/− mice. Therefore, SRC-3 maintains IGF-I in the circulation through enhancing VDR-regulated IGFBP-3 expression.

The Role of Insulin-like Growth Factor I(IGF-I), and IGF Binding Protein (IGFBP) in Mouse Lung Cancer Cells

2001 ◽  
Vol 50 (5) ◽  
pp. 549
Author(s):  
Chul Ho Cho ◽  
Se Kyu Kim ◽  
Seung Min Kwak ◽  
Joon Chang ◽  
Sung Kyu Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Mouse Lung ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein

Investigation of the mechanism of action of growth hormone in stimulating lactation in the rat

1992 ◽  
Vol 134 (3) ◽  
pp. 377-383 ◽  
Author(s):  
D. J. Flint ◽  
E. Tonner ◽  
J. Beattie ◽  
D. Panton
Keyword(s):  
Milk Production ◽  
Milk Yield ◽  
Combined Treatment ◽  
Concurrent Treatment ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

ABSTRACT The role of GH was examined using an antiserum to rat GH (anti-rGH). When administered to lactating rats on day 2 of lactation it was without effect, whereas bromocriptine markedly suppressed milk production, with no additional effect of combined treatment. On day 6 of lactation, treatment with anti-rGH was also without effect, whilst bromocriptine again suppressed milk production. Combined treatment, however, suppressed milk synthesis completely, suggesting that GH was capable of maintaining about 50% of normal milk yield in the absence of prolactin at day 6 of lactation. By day 14 of lactation, anti-rGH treatment alone was capable of decreasing milk yield by about 20%, and again milk secretion only stopped completely when GH and prolactin were suppressed. These data suggest that the role of GH in supporting lactation increases as lactation progresses. The effects of GH in stimulating growth and in increasing milk yield in ruminants have been proposed to be mediated via insulin-like growth factor-I (IGF-I). In rats treated with anti-rGH, both IGF-I and IGF-II were decreased in serum. The concentration of the major IGF-binding protein (IGFBP-3) was not, however, affected by inhibition of GH or prolactin individually, but was decreased in animals treated with bromocriptine and anti-rGH. In animals given both bromocriptine and anti-rGH, concurrent treatment with recombinant bovine GH maintained milk yield at 50% of control values and normalized serum IGF-I, IGF-II and IGFBP-3 concentrations. By contrast, concurrent treatment with IGF-I or IGF-II, despite normalizing their respective concentrations in serum, failed to affect milk yield. These results suggest that neither IGF-I nor IGF-II is capable of mediating the effects of GH alone. It is, however, possible that they play a part in a coordinated series of responses to GH involving IGF-I, IGF-II and IGFBP-3. Journal of Endocrinology (1992) 134, 377–383

Specimen processing time and measurement of total insulin-like growth factor-I (IGF-I), free IGF-I, and IGF binding protein-3 (IGFBP-3)

2006 ◽  
Vol 16 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Tiffany G. Harris ◽  
Howard D. Strickler ◽  
Herbert Yu ◽  
Michael N. Pollak ◽  
E. Scott Monrad ◽  
...  
Keyword(s):  
Growth Factor ◽  
Processing Time ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Specimen Processing ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3
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