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Structure‐Function Relationships of Growth Hormone and Other Members of the Growth Hormone Gene Family

John J. Kopchick, Wen Y. Chen

10.1002/cphy.cp070506

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 Studies Using Growth Hormone Fragments
2 Multiple Activities of Growth Hormone
3 Crystal Structure
4 Studies Regarding Disulfide Bonds
5 Homologue/Alanine Scanning as A Means of Defining Biologically Active Domains
6 The Third α‐Helix
6.1 Mutagenesis of the Growth Hormone Gene Encoding α‐Helix 3 and Transgenic Mouse Studies
6.2 Importance of the Amphiphilicity of the Third α‐Helix
6.3 Designing a Growth Hormone Analogue with a Perfect Amphiphilic α‐Helix
6.4 Systematic Substitution Mutations in the Hydrophilic Region of the Third α‐Helix of Bovine Growth Hormone
7 Growth Hormone Antagonists
7.1 Pegylated Growth Hormone Antagonists as Therapeutic Agents
8 Finding of One Growth Hormone/Two Growth Hormone‐Binding Proteins
9 Mutagenesis Studies on the Prolactin Gene
10 Concluding Remarks
Figure 1. Figure 1.

Amino acid sequence identity comparison among the growth hormone (GH) molecules from various species 119. The x axis represents the GH amino acid sequence from different species. The y axis represents the percentage of amino acid sequence identity as compared to hGH.
Figure 2. Figure 2.

Amino acid sequence of the human growth hormone molecule: 191 amino acids along with the two disulfide bonds.

Adapted from Li and Bewley 78
Figure 3. Figure 3.

Schematic representation of bovine growth hormone. Arrows indicate the trypsin cleavage sites located between amino acids 96 and 97, 132 and 133. Also shown are three α‐helical regions.

From Hara et al. 52
Figure 4. Figure 4.

Crystal representation of the porcine growth hormone molecule at the 2.8 Å resolution level. Four α‐helices are depicted (cylindrical rods). The nonhelical region is shown as a thin tube. Also, one of the two disulfide bonds is shown, while the other is hidden behind α‐helix 4. The amino‐(N) and carboxyl (C) termini are located in the upper left and lower left corners, respectively.

From Abdel‐Meguid et al. 1
Figure 5. Figure 5.

Axial projection—that is, conversion of a linear amino acid sequence into a two‐dimentional representation—of the third α‐helix 109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126 of native (A) and amino acid‐substituted (B) bovine growth hormone (bGH). Amino acid residues and corresponding hydrophilicity values are given. Amino acids in the open boxes are hydrophilic (top half of the wheel) and those in the shaded boxes are hydrophobic (bottom half). The glycine residue (position 119) is depicted with dots 22.
Figure 6. Figure 6.

Representative transgenic mice (2 months old, males) which express different (bGH) analogues. From left: transgenic mouse expressing bGH‐G119R; bGH‐A122D, which is similar in size to the nontransgenic mouse; and bGH‐E117L. All mice express ∼3–5 μg/ml of the bGH analogues in serum 21.
Figure 7. Figure 7.

Summary of transgenic mouse growth data 18. The x axis represents the individual transgenic lines. The y axis represents the mean growth ratio of pooled male and female transgenic mice between 2 and 4 months of age. Serum levels of bGH analogues ranged between 100 ng/ml and 10 μg/ml. There was no correlation between the serum levels of GH analogues and the degree of growth enhancement in transgenic animals with an enhanced‐growth phenotype. All standard deviations are within 15% of the mean.


Figure 1.

Amino acid sequence identity comparison among the growth hormone (GH) molecules from various species 119. The x axis represents the GH amino acid sequence from different species. The y axis represents the percentage of amino acid sequence identity as compared to hGH.



Figure 2.

Amino acid sequence of the human growth hormone molecule: 191 amino acids along with the two disulfide bonds.

Adapted from Li and Bewley 78


Figure 3.

Schematic representation of bovine growth hormone. Arrows indicate the trypsin cleavage sites located between amino acids 96 and 97, 132 and 133. Also shown are three α‐helical regions.

From Hara et al. 52


Figure 4.

Crystal representation of the porcine growth hormone molecule at the 2.8 Å resolution level. Four α‐helices are depicted (cylindrical rods). The nonhelical region is shown as a thin tube. Also, one of the two disulfide bonds is shown, while the other is hidden behind α‐helix 4. The amino‐(N) and carboxyl (C) termini are located in the upper left and lower left corners, respectively.

From Abdel‐Meguid et al. 1


Figure 5.

Axial projection—that is, conversion of a linear amino acid sequence into a two‐dimentional representation—of the third α‐helix 109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126 of native (A) and amino acid‐substituted (B) bovine growth hormone (bGH). Amino acid residues and corresponding hydrophilicity values are given. Amino acids in the open boxes are hydrophilic (top half of the wheel) and those in the shaded boxes are hydrophobic (bottom half). The glycine residue (position 119) is depicted with dots 22.



Figure 6.

Representative transgenic mice (2 months old, males) which express different (bGH) analogues. From left: transgenic mouse expressing bGH‐G119R; bGH‐A122D, which is similar in size to the nontransgenic mouse; and bGH‐E117L. All mice express ∼3–5 μg/ml of the bGH analogues in serum 21.



Figure 7.

Summary of transgenic mouse growth data 18. The x axis represents the individual transgenic lines. The y axis represents the mean growth ratio of pooled male and female transgenic mice between 2 and 4 months of age. Serum levels of bGH analogues ranged between 100 ng/ml and 10 μg/ml. There was no correlation between the serum levels of GH analogues and the degree of growth enhancement in transgenic animals with an enhanced‐growth phenotype. All standard deviations are within 15% of the mean.

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Article Title: Structure‐Function Relationships of Growth Hormone and Other Members of the Growth Hormone Gene Family
 

How to Cite

John J. Kopchick, Wen Y. Chen. Structure‐Function Relationships of Growth Hormone and Other Members of the Growth Hormone Gene Family. Compr Physiol 2011, Supplement 24: Handbook of Physiology, The Endocrine System, Hormonal Control of Growth: 145-162. First published in print 1999. doi: 10.1002/cphy.cp070506