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Insulin‐Like Growth Factor I Actions on Somatic Growth

J. Zapf, E. R. Froesch

10.1002/cphy.cp070521

Source: Supplement 24: Handbook of Physiology, The Endocrine System, Hormonal Control of Growth

Originally published: 1999

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Indirect Evidence that Insulin‐Like Growth Factor I Participates in the Regulation of Somatic Growth
1.1 Clinical: Correlations Between Growth and Insulin‐Like Growth Factor I Levels in Serum
1.2 Experimental: Growth Hormone‐Dependent Regulation of Insulin‐Like Growth Factor I mRNA and Protein Expression in Various Tissues and the Autocrine/Paracrine Versus Endocrine Role of Insulin‐Like Growth Factor I
2 Direct Evidence that Insulin‐Like Growth Factor I Promotes Growth
2.1 Insulin‐Like Growth Factor I as a Growth and Differentiation Factor In Vitro
2.2 Effects of Insulin‐Like Growth Factor I Administration on Growth In Vivo
2.3 Transgenic Animals Overexpressing Growth Hormone or Insulin‐Like Growth Factor I
2.4 Insulin‐Like Growth Factor I and Type 1 Insulin‐Like Growth Factor Receptor Knock‐Out Animals
2.5 The Somatomedin Hypothesis Revisited
Figure 1. Figure 1.

Dependence of immunoreactive (ir) serum insulin‐like growth factor I (IGF‐I) levels on chronological age and puberty in normal children. Mean levels and the 10th and 90th percentiles are given for Tanner stages P1 (closed circles and solid lines) and P2–P5 (open circles and broken lines). The number of subjects in each age group is between 20 and 100. The growth rate curve with the pubertal growth rate peaks for girls (stippled line) and boys (solid line).
Figure 2. Figure 2.

Left panel, dependence of insulin‐like growth factor I (IGF‐I) levels in serum as measured by radioimmunoassay on chronological age in girls (circles) as compared to those in boys (squares). The number of subjects in each group is between 10 and 80. Closed symbols represent mean values for all pubertal stages (P1–P5), open symbols represent mean values for pubertal stages P > 1, bars show the SEM (from J. Zapf and P. Sizonenko, unpublished). Right panel, height as percent of adult height plotted against chronological age for girls (broken line) and boys (solid line).

Modified from Prader 138, with permission
Figure 3. Figure 3.

Correlation between insulin‐like growth factor I (IGF‐I) levels in serum as measured by radioimmunoassay and growth rate in boys (left panel) and girls (right panel) during pubertal stages P1–P3.

From J. Zapf and P. Sizonenko, unpublished, with permission
Figure 4. Figure 4.

Age‐dependence of growth rate (left vertical axes) and insulin‐like growth factor I (IGF‐I) levels in serum as measured by radioimmunoassay (right vertical axes) in female (left panel) and male (right panel) pygmies and subjects of normal stature. Hatched columns show IGF‐I levels in pygmies, and open columns show IGF‐I levels in individuals of normal stature.

Modified from Merimee et al. 119, with permission
Figure 5. Figure 5.

Correlation between levels of growth hormone (GH) and insulin‐like growth factor I (IGF‐I) in serum as measured by radioimmunoassay in 24 acromegalic patients after surgical treatment or after radiotherapy or bromocriptine treatment. Upper panel, basal GH levels, lower panel, maximally suppressed GH levels after an oral glucose load.

Modified from Schatz et al. 162, with permission
Figure 6. Figure 6.

Effects of insulin‐like growth factor I (IGF‐I) on acetylcholine esterase activity as an index of muscle cell differentiation (A), and on cell multiplication (B) in primary chick embryo myoblasts after 4 days in culture. Columns give mean values of four different experiments each, and the bars indicate the SEM.

Modified from Schmid et al. 168, with permission
Figure 7. Figure 7.

Cell number and alkaline phosphatase activity (ratio of treated:control) in primary cultures of rat calvarium cells grown for 6 days in the absence or presence of increasing concentrations of insulin‐like growth factor I (IGF‐I).

From Schmid et al. 169 with permission
Figure 8. Figure 8.

Phase contrast micrographs of chick embryo myoblasts after 3 days of culture in the absence (A) and in the presence of 13 nM insulin‐like growth factor I (IGF‐I) (B).

From Schmid et al. 168 with permission
Figure 9. Figure 9.

Cell height (A) and cell volume (B) during the resting, proliferative, and hypertrophic phases of growth plate chondrocytes from the proximal tibia of hypophysectomized Wistar rats treated for 8 days with saline (stippled bars), 300 μg/d of rhIGF‐I (hatched bars), or 200 mU/d of rhGH (crosshatched bars), and of untreated age‐matched normal Wistar rats (open bars). (C and D) Electron micrographs of vertical sections through growth plate chondrocytes of the proximal tibia at the proliferative (C) and hypertrophic (D) activity phases. Upper left: untreated normal; upper right: saline‐treated hypophysectomized; lower left: rhIGF‐I‐treated; lower right: rhGH‐treated.

From Hunziker et al. 80 with permission
Figure 10. Figure 10.

(A) Cycle time (phase duration) and (B) cell turnover (cell number/column x day) of growth plate chondrocytes from the proximal tibia of hypophysectomized Wistar rats treated for 8 days with saline (stippled bars), 300 μg/d of rhIGF‐I (hatched bars) or 200 mU/d of rhGH (crosshatched bars), and of untreated, age‐matched, normal Wistar rats (open bars).

From Hunziker et al. 80 with permission
Figure 11. Figure 11.

Cell productivity (Δ cell height/hour, A cell volume/hour, and A matrix production/hour) in growth plate chondrocytes from the proximal tibia of hypophysectom Wistar rats treated for 8 days with saline (stippled bars), 300 μg/d of rhIGF‐I (hatched bars) or 200 mU/d of rhGH (crosshatched bars), and of untreated, age‐matched, normal Wistar rats (open bars).

From Hunziker et al. 80 with permission
Figure 12. Figure 12.

Molecular mass distribution of immunoreactive (ir) insulin‐like growth factor I (IGF‐I) in 1 ml serum of hypophysecto‐mized Wistar rats (same animals as in Figs. 21.21. 9–11) treated with saline, 200 mU/d of rhGH or 300 μg/d of rhIGF‐I, and in serum of untreated, age‐matched, normal Wistar rats. The sera were gel‐filtered over Sephadex G‐200, the fractions were pooled as indicated, dialyzed against 0.1 M NH4HCO3, lyophilized, dissolved in phosphate‐buffered saline‐0.2% human serum albumin, and then processed over SepPak columns to remove IGFBPs, as described in 204. IGF‐I was determined by radioimmunoassay. All points are the means of 3 gel filtration runs (2 runs for hypophysectomized controls). The bars indicate SEMs. When the [125I]iodo‐IGF‐I tracer was chromatographed on the same column, it eluted in pool 93–100.
Figure 13. Figure 13.

Serum insulin, serum insulin‐like growth factor I (IGF‐I) and blood sugar levels and growth indices in streptozotocin‐diabetic rats treated for 6 days with saline (diab.), 2.5 mg/d of rhIGF‐I, or 2.5 U/d of insulin (ins).

From Zapf et al., in preparation, with permission,
Figure 14. Figure 14.

Organ weights (expressed as g/100 g body weight) of streptozotocin‐diabetic rats treated for 6 days with saline (diab.), 2.5 mg/d of rhIGF‐I, or 2.5 U/d of insulin (ins.)

From Zapf et al., in preparation, with permission
Figure 15. Figure 15.

Cross sections through the thymus of a normal control rat (a) and of streptozotocin‐diabetic rats treated for 14 days with saline (b), 6 U/day of insulin (c), or 300 μg/day of rhIGF‐I (d). Staining was performed with hematoxilin/eosin. Magnification x 30.

From Binz et al. 18 with permission
Figure 16. Figure 16.

The somatomedin hypothesis revisited.


Figure 1.

Dependence of immunoreactive (ir) serum insulin‐like growth factor I (IGF‐I) levels on chronological age and puberty in normal children. Mean levels and the 10th and 90th percentiles are given for Tanner stages P1 (closed circles and solid lines) and P2–P5 (open circles and broken lines). The number of subjects in each age group is between 20 and 100. The growth rate curve with the pubertal growth rate peaks for girls (stippled line) and boys (solid line).



Figure 2.

Left panel, dependence of insulin‐like growth factor I (IGF‐I) levels in serum as measured by radioimmunoassay on chronological age in girls (circles) as compared to those in boys (squares). The number of subjects in each group is between 10 and 80. Closed symbols represent mean values for all pubertal stages (P1–P5), open symbols represent mean values for pubertal stages P > 1, bars show the SEM (from J. Zapf and P. Sizonenko, unpublished). Right panel, height as percent of adult height plotted against chronological age for girls (broken line) and boys (solid line).

Modified from Prader 138, with permission


Figure 3.

Correlation between insulin‐like growth factor I (IGF‐I) levels in serum as measured by radioimmunoassay and growth rate in boys (left panel) and girls (right panel) during pubertal stages P1–P3.

From J. Zapf and P. Sizonenko, unpublished, with permission


Figure 4.

Age‐dependence of growth rate (left vertical axes) and insulin‐like growth factor I (IGF‐I) levels in serum as measured by radioimmunoassay (right vertical axes) in female (left panel) and male (right panel) pygmies and subjects of normal stature. Hatched columns show IGF‐I levels in pygmies, and open columns show IGF‐I levels in individuals of normal stature.

Modified from Merimee et al. 119, with permission


Figure 5.

Correlation between levels of growth hormone (GH) and insulin‐like growth factor I (IGF‐I) in serum as measured by radioimmunoassay in 24 acromegalic patients after surgical treatment or after radiotherapy or bromocriptine treatment. Upper panel, basal GH levels, lower panel, maximally suppressed GH levels after an oral glucose load.

Modified from Schatz et al. 162, with permission


Figure 6.

Effects of insulin‐like growth factor I (IGF‐I) on acetylcholine esterase activity as an index of muscle cell differentiation (A), and on cell multiplication (B) in primary chick embryo myoblasts after 4 days in culture. Columns give mean values of four different experiments each, and the bars indicate the SEM.

Modified from Schmid et al. 168, with permission


Figure 7.

Cell number and alkaline phosphatase activity (ratio of treated:control) in primary cultures of rat calvarium cells grown for 6 days in the absence or presence of increasing concentrations of insulin‐like growth factor I (IGF‐I).

From Schmid et al. 169 with permission


Figure 8.

Phase contrast micrographs of chick embryo myoblasts after 3 days of culture in the absence (A) and in the presence of 13 nM insulin‐like growth factor I (IGF‐I) (B).

From Schmid et al. 168 with permission


Figure 9.

Cell height (A) and cell volume (B) during the resting, proliferative, and hypertrophic phases of growth plate chondrocytes from the proximal tibia of hypophysectomized Wistar rats treated for 8 days with saline (stippled bars), 300 μg/d of rhIGF‐I (hatched bars), or 200 mU/d of rhGH (crosshatched bars), and of untreated age‐matched normal Wistar rats (open bars). (C and D) Electron micrographs of vertical sections through growth plate chondrocytes of the proximal tibia at the proliferative (C) and hypertrophic (D) activity phases. Upper left: untreated normal; upper right: saline‐treated hypophysectomized; lower left: rhIGF‐I‐treated; lower right: rhGH‐treated.

From Hunziker et al. 80 with permission


Figure 10.

(A) Cycle time (phase duration) and (B) cell turnover (cell number/column x day) of growth plate chondrocytes from the proximal tibia of hypophysectomized Wistar rats treated for 8 days with saline (stippled bars), 300 μg/d of rhIGF‐I (hatched bars) or 200 mU/d of rhGH (crosshatched bars), and of untreated, age‐matched, normal Wistar rats (open bars).

From Hunziker et al. 80 with permission


Figure 11.

Cell productivity (Δ cell height/hour, A cell volume/hour, and A matrix production/hour) in growth plate chondrocytes from the proximal tibia of hypophysectom Wistar rats treated for 8 days with saline (stippled bars), 300 μg/d of rhIGF‐I (hatched bars) or 200 mU/d of rhGH (crosshatched bars), and of untreated, age‐matched, normal Wistar rats (open bars).

From Hunziker et al. 80 with permission


Figure 12.

Molecular mass distribution of immunoreactive (ir) insulin‐like growth factor I (IGF‐I) in 1 ml serum of hypophysecto‐mized Wistar rats (same animals as in Figs. 21.21. 9–11) treated with saline, 200 mU/d of rhGH or 300 μg/d of rhIGF‐I, and in serum of untreated, age‐matched, normal Wistar rats. The sera were gel‐filtered over Sephadex G‐200, the fractions were pooled as indicated, dialyzed against 0.1 M NH4HCO3, lyophilized, dissolved in phosphate‐buffered saline‐0.2% human serum albumin, and then processed over SepPak columns to remove IGFBPs, as described in 204. IGF‐I was determined by radioimmunoassay. All points are the means of 3 gel filtration runs (2 runs for hypophysectomized controls). The bars indicate SEMs. When the [125I]iodo‐IGF‐I tracer was chromatographed on the same column, it eluted in pool 93–100.



Figure 13.

Serum insulin, serum insulin‐like growth factor I (IGF‐I) and blood sugar levels and growth indices in streptozotocin‐diabetic rats treated for 6 days with saline (diab.), 2.5 mg/d of rhIGF‐I, or 2.5 U/d of insulin (ins).

From Zapf et al., in preparation, with permission,


Figure 14.

Organ weights (expressed as g/100 g body weight) of streptozotocin‐diabetic rats treated for 6 days with saline (diab.), 2.5 mg/d of rhIGF‐I, or 2.5 U/d of insulin (ins.)

From Zapf et al., in preparation, with permission


Figure 15.

Cross sections through the thymus of a normal control rat (a) and of streptozotocin‐diabetic rats treated for 14 days with saline (b), 6 U/day of insulin (c), or 300 μg/day of rhIGF‐I (d). Staining was performed with hematoxilin/eosin. Magnification x 30.

From Binz et al. 18 with permission


Figure 16.

The somatomedin hypothesis revisited.

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Article Title: Insulin‐Like Growth Factor I Actions on Somatic Growth
 

How to Cite

J. Zapf, E. R. Froesch. Insulin‐Like Growth Factor I Actions on Somatic Growth. Compr Physiol 2011, Supplement 24: Handbook of Physiology, The Endocrine System, Hormonal Control of Growth: 663-699. First published in print 1999. doi: 10.1002/cphy.cp070521