Comprehensive Physiology Wiley Online Library

Regulation of Growth Hormone Gene Expression

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Transcriptional Controls
1.1 Growth Hormone Gene Organization
1.2 Activation of Proximal Promoter Elements of the Growth Hormone Gene in Somatotropes
1.3 Structure and Function of the Proximal Promoter
1.4 Activation of Placentally Expressed Human Growth Hormone Genes
1.5 Role of Silencer Elements
1.6 Genetic Evidence for Transcriptional Control and Developmental Pathways
2 Posttranscriptional Controls
2.1 Alternative Splicing of Human Growth Hormone Genes
2.2 Alternative Splicing of the Bovine Growth Hormone Gene
2.3 mRNA Stability
Figure 1. Figure 1.

The human growth hormone (hGH) gene cluster. The chromosomal location of the cluster is noted. Each of the five genes is indicated on the first line by a labeled rectangle. Patterns of expression in pituitary or placenta are outlined on the second and third lines, respectively. The location of the DNasel hypersensitivity site present in the chromatin of pituitary somatotrope and placental syncytiotrophoblast nuclei is shown 5′ to the cluster. The presence of a hypersensitive site 3′ to the cluster in the pituitary is hypothetical and so denoted by ?. The protein products of each of the genes are listed below the arrows leading from each gene. It remains unclear whether any protein is expressed by the hCS‐L gene. hGH‐N, pituitary GH; hGH‐V, hGH‐variant; hCS‐L, chorionic somatomammotropin‐like; hCS‐A, chorionic somatomammotropin‐A; hCS‐B, chorionic somatomammotropin‐B.

Figure 2. Figure 2.

The human growth hormone (hGH) locus. A 100 kb region encompassing the linked skeletal muscle sodium‐channel gene (SCN4A), the B‐lymphocyte receptor gene (CD79b), and the GH cluster (containing the five indicated genes) is shown. Exons of the SCN4A and the CD79b genes are shown as numbered boxes. The five exons of each of the five genes in the GH cluster are shown but not numbered. The positions of the locus‐control region DNasel hypersensitive sites associated with GH cluster gene expression are indicated below the diagram.

Figure 3. Figure 3.

The growth hormone (GH) gene promoter. Generalized diagram of the human and rodent GH promoter is shown. The start of transcription is marked by the angled arrow, and the polymerase‐binding site common to many eukaryotic genes (TATA box) and the positions at which a variety of transcription control factors bind to this promoter are noted. The thyroid hormone receptor (T3R), which is specific to the rat GH gene promoter, and the cAMP‐response element (CRE), which is specific to the human, are shown above and below the line, respectively. The two Pit‐1‐binding sites, one proximal (pPit) and one distal (dPit) relative to the promoter, are indicated.

Figure 4. Figure 4.

Diagram of the rat pit‐1 promoter. The positions of the two Pit‐1‐binding sites, PitB1 and PitB2, are shown, as are the two cAMP‐response elements, CRE1 and CRE2. Note that one of the Pit‐1‐binding sites, PitB2, is located 3′ from the site of transcription initiation.

From Chen et al. with permission
Figure 5. Figure 5.

The Pit‐1 trans‐activator protein. General diagram identifying the major N‐terminal transcription activation domain and the composite DNA‐binding domain composed of the two DNA‐binding subdomains, a POU‐specific domain (POUs) and a POU homeodomain (POUHD). The positioning of the conserved α‐helical regions within the two POU domains is shown by the dark ovals.



Figure 1.

The human growth hormone (hGH) gene cluster. The chromosomal location of the cluster is noted. Each of the five genes is indicated on the first line by a labeled rectangle. Patterns of expression in pituitary or placenta are outlined on the second and third lines, respectively. The location of the DNasel hypersensitivity site present in the chromatin of pituitary somatotrope and placental syncytiotrophoblast nuclei is shown 5′ to the cluster. The presence of a hypersensitive site 3′ to the cluster in the pituitary is hypothetical and so denoted by ?. The protein products of each of the genes are listed below the arrows leading from each gene. It remains unclear whether any protein is expressed by the hCS‐L gene. hGH‐N, pituitary GH; hGH‐V, hGH‐variant; hCS‐L, chorionic somatomammotropin‐like; hCS‐A, chorionic somatomammotropin‐A; hCS‐B, chorionic somatomammotropin‐B.



Figure 2.

The human growth hormone (hGH) locus. A 100 kb region encompassing the linked skeletal muscle sodium‐channel gene (SCN4A), the B‐lymphocyte receptor gene (CD79b), and the GH cluster (containing the five indicated genes) is shown. Exons of the SCN4A and the CD79b genes are shown as numbered boxes. The five exons of each of the five genes in the GH cluster are shown but not numbered. The positions of the locus‐control region DNasel hypersensitive sites associated with GH cluster gene expression are indicated below the diagram.



Figure 3.

The growth hormone (GH) gene promoter. Generalized diagram of the human and rodent GH promoter is shown. The start of transcription is marked by the angled arrow, and the polymerase‐binding site common to many eukaryotic genes (TATA box) and the positions at which a variety of transcription control factors bind to this promoter are noted. The thyroid hormone receptor (T3R), which is specific to the rat GH gene promoter, and the cAMP‐response element (CRE), which is specific to the human, are shown above and below the line, respectively. The two Pit‐1‐binding sites, one proximal (pPit) and one distal (dPit) relative to the promoter, are indicated.



Figure 4.

Diagram of the rat pit‐1 promoter. The positions of the two Pit‐1‐binding sites, PitB1 and PitB2, are shown, as are the two cAMP‐response elements, CRE1 and CRE2. Note that one of the Pit‐1‐binding sites, PitB2, is located 3′ from the site of transcription initiation.

From Chen et al. with permission


Figure 5.

The Pit‐1 trans‐activator protein. General diagram identifying the major N‐terminal transcription activation domain and the composite DNA‐binding domain composed of the two DNA‐binding subdomains, a POU‐specific domain (POUs) and a POU homeodomain (POUHD). The positioning of the conserved α‐helical regions within the two POU domains is shown by the dark ovals.

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How to Cite

Nancy E. Cooke, Stephen A. Liebhaber. Regulation of Growth Hormone Gene Expression. Compr Physiol 2011, Supplement 24: Handbook of Physiology, The Endocrine System, Hormonal Control of Growth: 163-185. First published in print 1999. doi: 10.1002/cphy.cp070507