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Gene Review

GH2  -  growth hormone 2

Homo sapiens

Synonyms: GH-V, GHL, GHV, Growth hormone 2, Growth hormone variant, ...
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Disease relevance of GH2

  • Hybridization experiments were performed between dot-blotted mRNA originating either from placenta or from one pituitary hGH secreting adenoma and synthetic polynucleotide probes corresponding to specific portions of the hGH-V or hGH-N gene sequences [1].
  • Expression plasmids containing DNA sequences optimized for expression in Escherichia coli were prepared encoding human pituitary (hGH-N 20K) and placental (hGH-V 20 and 22K) growth hormones [2].
  • Peak hGH-V levels occurred at wk 36.5 +/- 2.6 and were significantly lower in obese (P = 0.029) and higher in underweight (P = 0.035) mothers compared with those in mothers of normal weight [3].
  • In choriocarcinoma JAR cells, hGH-V RNA represented approximately 78% of the total hGH/hCS RNA compared to approximately 22% for hCS [4].
  • GH-V products, which are hallmarks of the normal healthy testis, were not detected in any testicular cancer specimen (0 of 16) [5].

High impact information on GH2

  • The plasma tripeptide glycyl-L-lysine (GHL), when added at nanomolar concentrations to a wide group of cultured systems, produces a disparate set of responses ranging from the stimulation of growth and differentiation to outright toxicity [6].
  • DNA fragments of 2.6, 2.8, and 9.5 kilobase pairs containing GH, CSH, and GHL, respectively, were identified in human genomic DNA, and a 7.5-kilobase DNA fragment related to growth hormone DNA sequences was found in mouse cells [7].
  • In the present report, we document the expression of both of these hGH-V mRNA species in the villi of the term placenta, demonstrate an increase in their concentrations during gestation, and directly sublocalize hGH-V gene expression to the syncytiotrophoblastic epithelium of the term placenta by in situ cDNA-mRNA histohybridization [8].
  • The human growth hormone-variant (hGH-V) gene is one of five highly similar growth hormone-related genes clustered on the short arm of chromosome 17 [8].
  • Stably transfected cell lines containing the normal human growth hormone (hGH-N) and human growth hormone-variant (hGH-V) genes have been established in order to study the expression of these two highly homologous genes [9].

Biological context of GH2

  • Eleven novel mutations in the GH1 gene promoter were assessed by reporter gene assay but only two, including a GH2 gene-templated gene conversion, were found to be associated with a significantly reduced level of expression [10].
  • The proportion of alternatively spliced hGH-V transcripts that retain intron 4 is also developmentally regulated, increasing 3-fold during gestation to 15% at term [11].
  • The alternative splicing generating hGH-V3 was only demonstrated in transcripts derived from the hGH-V gene [12].
  • Loss of GH-V gene expression in testicular GCT compared with normal testis and loss (seminoma) or mutation (NSGCT) of PLL gene products might have significance in terms of the relationship between these tumors and for testicular GCT development [5].
  • DNA sequence analysis and polymerase chain reaction amplification between two sequences located on each side of the deletion breakpoint accurately identified the deletion breakpoints and indicated that the regulatory sequences located upstream from the TATA box of the mutant CS-B belong to the GH-2 gene [13].

Anatomical context of GH2


Associations of GH2 with chemical compounds

  • GH3.3 reduced by 30% the rate of leucine oxidation (P = 0.0069 vs. basal) and increased by 11% nonoxidative leucine disposal (P = 0.0095 vs. basal) and by 21% glycerol Ra (0.0035 vs. basal); GH2 and placebo had no significant effect [16].
  • To determine whether any of these hGH-V isoforms are glycosylated, the cell lines were grown in the absence and presence of tunicamycin [17].
  • In order to evaluate the mechanism(s) whereby opiods induce GH secretion in man, we gave the following treatments to six healthy male volunteers: (a) IV saline; (b) a met-enkephalin analog G-DAMME 250 micrograms IV as a bolus at time 0'; (c) hGH 2 IU as an IV bolus at time -180'; (d) G-DAMME as above, preceded by hGH as above [18].
  • Unsaturated fatty acids at microM concentrations inhibited protein synthesis in intact GH2 pituitary, C6 glial tumour and HeLa cells in a manner dependent on degree of unsaturation and cell number [19].
  • The ocs element in the soybean GH2/4 promoter is activated by both active and inactive auxin and salicylic acid analogues [20].

Physical interactions of GH2

  • The presence of Pit-1-binding sites in the CS-A and GH-V promoter regions predicts that Pit-1 may be expressed in the placenta [21].
  • The comparable somatogen, but lower lactogen, bioactivity of hGH-V relative to hGH-N parallels the previously reported receptor binding profiles of the two hormones and suggests that hGH-V has the potential to perform a unique role during human gestation [22].

Regulatory relationships of GH2

  • Like hGH, signaling by GH-V is inhibited by the GH antagonist (G120K) [23].
  • These results provide preliminary evidence that GH-V plays a major role in affecting target cells expressing the GH receptor, thus potentially exerting significant GH-like effects on maternal physiology during pregnancy [23].
  • GH-V activates the STAT5b transcription factor in the IM-9 human lymphocyte and 3T3-F442A preadipocyte cell lines, and in primary porcine smooth muscle cells, which all homologously express GH receptors [23].

Other interactions of GH2

  • An Sx Alu repeat lies in close proximity to the hGH-1 and hGH-2 genes in the 3'-flanking region [24].
  • Levels of hCS-A, hCS-B, and hGH-V transcripts are all elevated [25].
  • Binding experiments using hGHR-ECD revealed that the differences between the two 22K variants or between the two 20K variants were not significant, except that hGH-V 20K exhibited slightly lower affinity [2].
  • In conclusion, hGH-V mRNA is expressed by cells other than the syncytiotrophoblast, is not regulated by PIT-1, and may be involved in immune regulation, as is pituitary GH [26].
  • The carboxy-terminal sequence of hGH-V3 differs from 22-kDa hGH-V and hGH-V2, the two previously reported transcripts of the hGH-V gene, and does not contain a predicted transmembrane domain as described for hGH-V2 [12].

Analytical, diagnostic and therapeutic context of GH2

  • Cellular and secreted proteins from BeWo cells were analyzed by Western blotting, and a band of about 22 kilodaltons was detected using a polyclonal antibody which cross-reacts with hGH-V and hCS [25].
  • In situ hybridization was then performed to locate the GH-V mRNA encoding placental growth hormone [14].
  • The activity of hGH-V 22K was ninefold less in Nb2 cells and 55-fold less in Baf/3 cells, whereas hGH-V 20K had no lactogenic activity in either bioassay [2].
  • Circular dichroism (CD) analysis revealed similarity of the purified hGHs' secondary structure to that of the pituitary hGH-N 22K, except for hGH-V 20K, in which the alpha-helix content was lower [2].
  • The coding region of the hGH-V gene was amplified by RT-PCR using placental complementary DNA as template [12].


  1. Expression of the growth hormone variant gene in human placenta. Frankenne, F., Rentier-Delrue, F., Scippo, M.L., Martial, J., Hennen, G. J. Clin. Endocrinol. Metab. (1987) [Pubmed]
  2. Large-scale preparation and in vitro characterization of biologically active human placental (20 and 22K) and pituitary (20K) growth hormones: Placental growth hormones have no lactogenic activity in humans. Solomon, G., Reicher, S., Gussakovsky, E.E., Jomain, J.B., Gertler, A. Growth Horm. IGF Res. (2006) [Pubmed]
  3. A new nonisotopic, highly sensitive assay for the measurement of human placental growth hormone: development and clinical implications. Wu, Z., Bidlingmaier, M., Friess, S.C., Kirk, S.E., Buchinger, P., Schiessl, B., Strasburger, C.J. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  4. Detection of placental growth hormone variant and chorionic somatomammotropin ribonucleic acid expression in human trophoblastic neoplasms by reverse transcriptase-polymerase chain reaction. Lytras, A., Bock, M.E., Dodd, J.G., Cattini, P.A. Endocrinology (1994) [Pubmed]
  5. The testis-specific expression pattern of the growth hormone/placental lactogen (GH/PL) gene cluster changes with malignancy. Berger, P., Untergasser, G., Hermann, M., Hittmair, A., Madersbacher, S., Dirnhofer, S. Hum. Pathol. (1999) [Pubmed]
  6. Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Pickart, L., Freedman, J.H., Loker, W.J., Peisach, J., Perkins, C.M., Stenkamp, R.E., Weinstein, B. Nature (1980) [Pubmed]
  7. Genes for growth hormone, chorionic somatommammotropin, and growth hormones-like gene on chromosome 17 in humans. Owerbach, D., Rutter, W.J., Martial, J.A., Baxter, J.D., Shows, T.B. Science (1980) [Pubmed]
  8. Characterization and histologic localization of human growth hormone-variant gene expression in the placenta. Liebhaber, S.A., Urbanek, M., Ray, J., Tuan, R.S., Cooke, N.E. J. Clin. Invest. (1989) [Pubmed]
  9. Human growth hormone gene and the highly homologous growth hormone variant gene display different splicing patterns. Cooke, N.E., Ray, J., Watson, M.A., Estes, P.A., Kuo, B.A., Liebhaber, S.A. J. Clin. Invest. (1988) [Pubmed]
  10. Novel mutations of the growth hormone 1 (GH1) gene disclosed by modulation of the clinical selection criteria for individuals with short stature. Millar, D.S., Lewis, M.D., Horan, M., Newsway, V., Easter, T.E., Gregory, J.W., Fryklund, L., Norin, M., Crowne, E.C., Davies, S.J., Edwards, P., Kirk, J., Waldron, K., Smith, P.J., Phillips, J.A., Scanlon, M.F., Krawczak, M., Cooper, D.N., Procter, A.M. Hum. Mutat. (2003) [Pubmed]
  11. Developmental control and alternative splicing of the placentally expressed transcripts from the human growth hormone gene cluster. MacLeod, J.N., Lee, A.K., Liebhaber, S.A., Cooke, N.E. J. Biol. Chem. (1992) [Pubmed]
  12. Cloning of two novel growth hormone transcripts expressed in human placenta. Boguszewski, C.L., Svensson, P.A., Jansson, T., Clark, R., Carlsson, L.M., Carlsson, B. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  13. Isolated growth hormone deficiency type IA associated with a 45-kilobase gene deletion within the human growth hormone gene cluster in an Italian family. Ghizzoni, L., Duquesnoy, P., Torresani, T., Vottero, A., Goossens, M., Bernasconi, S. Pediatr. Res. (1994) [Pubmed]
  14. Syncytiotrophoblastic localization of the human growth hormone variant mRNA in the placenta. Scippo, M.L., Frankenne, F., Hooghe-Peters, E.L., Igout, A., Velkeniers, B., Hennen, G. Mol. Cell. Endocrinol. (1993) [Pubmed]
  15. Evidence for the expression of growth hormone receptors in human placenta. Frankenne, F., Alsat, E., Scippo, M.L., Igout, A., Hennen, G., Evain-Brion, D. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  16. A dose-response study of growth hormone (GH) replacement on whole body protein and lipid kinetics in GH-deficient adults. Lucidi, P., Lauteri, M., Laureti, S., Celleno, R., Santoni, S., Volpi, E., Angeletti, G., Santeusanio, F., De Feo, P. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  17. Glycosylated human growth hormone variant. Ray, J., Jones, B.K., Liebhaber, S.A., Cooke, N.E. Endocrinology (1989) [Pubmed]
  18. Effect of exogenous growth hormone administration on endogenous growth hormone secretion induced by a met-enkephalin analog. Fanciulli, G., Oliva, O., Tomasi, P.A., Pala, A., Bertoncelli, A., Dettori, A., Delitala, G. Eur. J. Endocrinol. (1996) [Pubmed]
  19. Inhibition of protein synthesis in intact mammalian cells by arachidonic acid. Rotman, E.I., Brostrom, M.A., Brostrom, C.O. Biochem. J. (1992) [Pubmed]
  20. The ocs element in the soybean GH2/4 promoter is activated by both active and inactive auxin and salicylic acid analogues. Ulmasov, T., Hagen, G., Guilfoyle, T. Plant Mol. Biol. (1994) [Pubmed]
  21. Expression of pit-1 messenger ribonucleic acid and protein in the human placenta. Bamberger, A.M., Bamberger, C.M., Pu, L.P., Puy, L.A., Loh, Y.P., Asa, S.L. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  22. Human growth hormone-variant is a biologically active somatogen and lactogen. MacLeod, J.N., Worsley, I., Ray, J., Friesen, H.G., Liebhaber, S.A., Cooke, N.E. Endocrinology (1991) [Pubmed]
  23. Intracellular signaling by growth hormone variant (GH-V). Silva, C.M., Kloth, M.T., Lyons, C.E., Dunn, C.R., Kirk, S.E. Growth Horm. IGF Res. (2002) [Pubmed]
  24. The Human Growth Hormone Gene Contains a Silencer Embedded within an Alu Repeat in the 3'-Flanking Region. Trujillo, M.A., Sakagashira, M., Eberhardt, N.L. Mol. Endocrinol. (2006) [Pubmed]
  25. Tissue-specific expression and thyroid hormone regulation of the endogenous placental growth hormone variant and chorionic somatomammotropin genes in a human choriocarcinoma cell line. Nickel, B.E., Cattini, P.A. Endocrinology (1991) [Pubmed]
  26. Both pituitary and placental growth hormone transcripts are expressed in human peripheral blood mononuclear cells (PBMC). Melen, L., Hennen, G., Dullaart, R.P., Heinen, E., Igout, A. Clin. Exp. Immunol. (1997) [Pubmed]
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