Alternative titles; symbols
HGNC Approved Gene Symbol: GH2
Cytogenetic location: 17q23.3 Genomic coordinates (GRCh38): 17:63,880,215-63,881,944 (from NCBI)
Lewis et al. (1978) described a structural variant of human growth hormone (GH1; 139250), which they called growth hormone-2, or GH2. Its molecular mass was estimated to be about 20 kD, whereas GH1 has a molecular mass of about 22 kD. The variant had several amino acid differences and reacted poorly with antibody to human growth hormone. Seeburg (1982) studied the structure of the GH2 gene, which they referred to as the GHV gene, and Pavlakis et al. (1981) studied the protein resulting from its in vitro expression. Frankenne et al. (1987) showed that a placental variant of growth hormone, which appears in maternal serum in midpregnancy and rises in concentration thereafter to term, is the product of the GHV gene. The GHV gene is not expressed in the pituitary. Liebhaber et al. (1989) showed that the GHV gene is expressed in the term placenta, specifically in the syncytiotrophoblastic epithelium. The similarity in developmental and tissue-specific expression to that of the related CSA (150200) and CSB (118820) genes suggested that these genes may share common regulatory elements.
The GH2 gene differs from the GH1 gene by the presence of a GT-to-AT transition at the 5-prime donor splice site of intron 2 (Chen et al., 1989). A cryptic site develops at nucleotide +19.
Boguszewski et al. (1998) noted that the GHN (GH1) and GHV (GH2) genes consist of 5 exons. They examined alternative splicing of GHV transcripts. The coding region of the GHV gene was amplified by RT-PCR using placental cDNA as template. DNA sequencing of several clones revealed 2 novel transcripts. One transcript isoform had a 45-bp deletion caused by the use of an alternative 3-prime splice site in exon 3, similar to that in the GH1 gene, and is predicted to encode a 20-kD GHV protein isoform. The other transcript isoform arose by the use of an alternative 5-prime splice site which caused a 4-bp deletion in the end of exon 4 and is predicted to encode a 24-kD protein with 219 amino acids, which the authors referred to as GHV3. The carboxy-terminal sequence of GHV3 differs from those of 22-kD GHV and GHV2, the 2 previously reported transcripts of the GHV gene, and does not contain a predicted transmembrane domain as described for GHV2. The authors concluded that the GHV transcript undergoes alternative splicing pathways that can generate at least 4 different mRNA isoforms, predicting the expression of different GH protein products, including 2 with a complete sequence divergence in the carboxy terminus.
Chellakooty et al. (2004) evaluated the association of maternal serum levels of placental GH and IGF1 (147440) with fetal growth in a prospective longitudinal study of 89 normal pregnant women. Placental GH levels were detectable in all samples from as early as 5 weeks' gestation and increased significantly throughout pregnancy until approximately 37 weeks' gestation, when peak levels of 22 ng/ml were reached. Subsequently, placental GH levels decreased until birth. The change in placental GH during 24.5 to 37.5 weeks' gestation was positively associated with fetal growth rate (P = 0.027) and birth weight (P = 0.027). Gestational age at peak placental GH values (P = 0.007) was associated with pregnancy length. A positive association between the change in placental GH and the change in IGF1 levels throughout gestation was found in a multivariate analysis (r(2) = 0.42; P less than 0.001).
By combination of restriction mapping with somatic cell hybridization, Owerbach et al. (1980) localized the GH2 gene, which they called 'growth hormone-like' (GHL), to chromosome 17.
MacLeod et al. (1991) found abnormally large GHV mRNAs in 1 of 20 placentas. Sequence analysis demonstrated retention of the first 12 bases of intron 2, resulting from both a base substitution at the intron 2 splice-donor dinucleotide (GT to AT) and activation of a cryptic splice-donor site 12 bases downstream. Survey of a total of 60 additional chromosomes failed to reveal other instances of this mutation. While the importance of GHV to fetal and maternal physiology remained to be defined, MacLeod et al. (1991) demonstrated by bioassays that it has a strong somatogen activity. MacLeod et al. (1991) found no direct evidence to suggest that the splice site mutation in the heterozygous state has a significant adverse effect on the physiology of pregnancy, labor, delivery, or fetal development.
Boguszewski, C. L., Svensson, P.-A., Jansson, T., Clark, R., Carlsson, L. M. S., Carlsson, B. Cloning of two novel growth hormone transcripts expressed in human placenta. J. Clin. Endocr. Metab. 83: 2878-2885, 1998. [PubMed: 9709963] [Full Text: https://doi.org/10.1210/jcem.83.8.5017]
Chellakooty, M., Vangsgaard, K., Larsen, T., Scheike, T., Falck-Larsen, J., Legarth, J., Andersson, A. M., Main, K. M., Skakkebaek, N. E., Juul, A. A longitudinal study of intrauterine growth and the placental growth hormone (GH)-insulin-like growth factor I axis in maternal circulation: association between placental GH and fetal growth. J. Clin. Endocr. Metab. 89: 384-391, 2004. [PubMed: 14715876] [Full Text: https://doi.org/10.1210/jc.2003-030282]
Chen, E. Y., Liao, Y.-C., Smith, D. H., Barrera-Saldana, H. A., Gelinas, R. E., Seeburg, P. H. The human growth hormone locus: nucleotide sequence, biology, and evolution. Genomics 4: 479-497, 1989. [PubMed: 2744760] [Full Text: https://doi.org/10.1016/0888-7543(89)90271-1]
Frankenne, F., Rentier-Delrue, F., Scippo, M.-L., Martial, J., Hennen, G. Expression of the growth hormone variant gene in human placenta. J. Clin. Endocr. Metab. 64: 635-637, 1987. [PubMed: 3818895] [Full Text: https://doi.org/10.1210/jcem-64-3-635]
Lewis, U. J., Dunn, J. T., Bonewald, L. F., Seavey, B. K., VanderLaan, W. P. A naturally occurring structural variant of human growth hormone. J. Biol. Chem. 253: 2679-2687, 1978. [PubMed: 632293]
Liebhaber, S. A., Urbanek, M., Ray, J., Tuan, R. S., Cooke, N. E. Characterization and histologic localization of human growth hormone-variant gene expression in the placenta. J. Clin. Invest. 83: 1985-1991, 1989. [PubMed: 2723069] [Full Text: https://doi.org/10.1172/JCI114108]
MacLeod, J. N., Liebhaber, S. A., MacGillivray, M. H., Cooke, N. E. Identification of a splice-site mutation in the human growth hormone-variant gene. Am. J. Hum. Genet. 48: 1168-1174, 1991. [PubMed: 2035535]
MacLeod, J. N., Worsley, I., Ray, J., Friesen, H. G., Liebhaber, S. A., Cooke, N. E. Human growth hormone variant is a biologically active somatogen and lactogen. Endocrinology 128: 1298-1302, 1991. [PubMed: 1999151] [Full Text: https://doi.org/10.1210/endo-128-3-1298]
Owerbach, D., Rutter, W. J., Martial, J. A., Baxter, J. D., Shows, T. B. Genes for growth hormone, chorionic somatomammotropin and growth hormone-like genes on chromosome 17 in humans. Science 209: 289-292, 1980. [PubMed: 7384802] [Full Text: https://doi.org/10.1126/science.7384802]
Pavlakis, G. N., Hizuka, N., Gorden, P., Seeburg, P. H., Hamber, D. H. Expression of two human growth hormone genes in monkey cells infected by simian virus 40 recombinants. Proc. Nat. Acad. Sci. 78: 7398-7402, 1981. [PubMed: 6174972] [Full Text: https://doi.org/10.1073/pnas.78.12.7398]
Seeburg, P. H. The human growth hormone gene family: nucleotide sequences show recent divergence and predict a new polypeptide hormone. DNA 1: 239-249, 1982. [PubMed: 7169009] [Full Text: https://doi.org/10.1089/dna.1.1982.1.239]