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Gene Review

Ggh  -  gamma-glutamyl hydrolase (conjugase,...

Rattus norvegicus

Synonyms: Conjugase, GH, Gamma-Glu-X carboxypeptidase, Gamma-glutamyl hydrolase
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Disease relevance of Ggh

  • Purified gamma-glutamyl hydrolase secreted from rat H35 hepatoma cells has been characterized as a diffuse band of 55 kDa on SDS-polyacrylamide gel electrophoresis that is converted to bands of 35 and 33 kDa after enzymatic removal of N-linked carbohydrate [1].
  • 3,5,3'-Triiodo-L-thyronine (T3) regulates the growth rate and GH production of cultured GC cells, a rat pituitary tumor cell line [2].
  • The role of the pituitary-specific POU-domain protein, Pit-1, in GH gene activation has been established by in vitro analyses and by the observation that mutations affecting the Pit-1 genomic locus result in genetically transmitted dwarfism [3].
  • 10-Formylpteroylpentaglutamate (2.0nmol/g) and 10-formylpteroyltetraglutamate (0.25nmol/g) comprised about 20% of the total endogenous hepatic folate as determined by microbiological assay (Lactobacillus casei after conjugase treatment [4].
  • Induction of hyperthyroidism did not further increase GH mRNA levels above control, but increased PRL mRNA levels 2-fold over control [5].

High impact information on Ggh


Chemical compound and disease context of Ggh

  • 5-Azacytidine increased rGH mRNA 3-8-fold in GH3D6 cells, a subclone of rat pituitary tumor cell lines that expresses one-tenth to one-fifteenth the GH expressed by two other clones, GH3 and GC [8].
  • Testosterone enhanced weight gain in the rats treated for 10 days, a change that was similar in the presence or absence of GH [9].
  • Diabetes was induced by the administration of streptozotocin (STZ; 10 mg/100 g body weight) and 3 days later GH and ACTH protein and mRNA were determined [10].
  • The aim of this study was to evaluate whether a chronic treatment with hexarelin, a synthetic enkephalin-derived hexapeptide with a potent GH-releasing activity, might be able to ameliorate the somatotropic function and reverse some metabolic alterations associated with obesity in male obese Zucker rats [11].
  • Genetically obese male Zucker rats have an impaired secretion of GH, coupled to hyperinsulinemia, hyperlipidemia and glucose intolerance [11].

Biological context of Ggh


Anatomical context of Ggh


Associations of Ggh with chemical compounds

  • Third, within the sensitivities of the assay methods, 5-azacytidine has no effect on the GH gene when it is completely silent [8].
  • The elements of the rat GH gene important for thyroid hormone stimulation and cell-specific expression have been previously mapped using gene transfection techniques [16].
  • JAK2 signaling to STAT5b at the conclusion of a GH pulse could be sustained by the protein synthesis inhibitor cycloheximide or by the proteasome inhibitor MG132, indicating that termination of this JAK2-catalyzed STAT activation loop requires synthesis of a labile or GH-inducible protein factor and is facilitated by the proteasome pathway [13].
  • Diabetes was induced by the administration of streptozotocin (7 mg/100 g BW), and 18 days later, GH content, GH mRNA, and GH transcription rate were determined [12].
  • Ikaros does not bind directly to the proximal GH promoter but abrogates the effect of the histone deacetylation inhibitor trichostatin A on this region [17].

Analytical, diagnostic and therapeutic context of Ggh

  • Estrogens increased GH mRNA levels and decreased PRL mRNA levels as detected by in situ hybridization and Northern blot hybridization with oligonucleotide probes, while inhibiting tumor growth [7].
  • High pressure liquid chromatography analysis, conjugase digestion, double radiolabel studies, and amino acid analysis of acid-hydrolyzed product confirmed that folylpoly-gamma-glutamates were synthesized [18].
  • Thyroidectomy decreased GH and GH mRNA to less than 5% of the values found in intact animals, and a single saturating injection of T3 (250 micrograms/100 g BW) resulted in a 8- to 10-fold induction of GH mRNA after 6 h.(ABSTRACT TRUNCATED AT 250 WORDS)[12]
  • STAT5b (signal transducer and activator of transcription 5b) is a key mediator of the effects of plasma GH pulses on male-specific liver gene expression [13].
  • In electrophoretic mobility shift assays, ALS-GAS1 formed a specific, GH-dependent protein-DNA complex with nuclear extracts from H4-II-E cells [19].


  1. Identification, cloning, and sequencing of a cDNA coding for rat gamma-glutamyl hydrolase. Yao, R., Nimec, Z., Ryan, T.J., Galivan, J. J. Biol. Chem. (1996) [Pubmed]
  2. Regulation of growth hormone mRNA synthesis by 3,5,3'-triiodo-L-thyronine in cultured growth hormone-producing rat pituitary tumor cells (GC cells). Dissociation between nuclear iodothyronine receptor concentration and growth hormone mRNA synthesis during the deoxyribonucleic acid synthesis phase of the cell cycle. Kumara-Siri, M.H., Surks, M.I. J. Biol. Chem. (1985) [Pubmed]
  3. Synergistic interactions between Pit-1 and other elements are required for effective somatotroph rat growth hormone gene expression in transgenic mice. Lira, S.A., Kalla, K.A., Glass, C.K., Drolet, D.W., Rosenfeld, M.G. Mol. Endocrinol. (1993) [Pubmed]
  4. The identification of the folate conjugates found in rat liver 48 h after the administration of radioactively labelled folate tracers. Connor, M.J., Blair, J.A. Biochem. J. (1980) [Pubmed]
  5. The effect of altered thyroid status on pituitary hormone messenger ribonucleic acid concentrations in the rat. Samuels, M.H., Wierman, M.E., Wang, C., Ridgway, E.C. Endocrinology (1989) [Pubmed]
  6. Human gamma-glutamyl hydrolase: cloning and characterization of the enzyme expressed in vitro. Yao, R., Schneider, E., Ryan, T.J., Galivan, J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  7. The effects of estrogens on tumor growth and on prolactin and growth hormone mRNA expression in rat pituitary tissues. Lloyd, R.V., Cano, M., Landefeld, T.D. Am. J. Pathol. (1988) [Pubmed]
  8. The effects of 5-azacytidine on the expression of the rat growth hormone gene. Methylation modulates but does not control growth hormone gene activity. Lan, N.C. J. Biol. Chem. (1984) [Pubmed]
  9. Testosterone effect on growth and growth mediators of the GH-IGF-I axis in the liver and epiphyseal growth plate of juvenile rats. Zung, A., Phillip, M., Chalew, S.A., Palese, T., Kowarski, A.A., Zadik, Z. J. Mol. Endocrinol. (1999) [Pubmed]
  10. Effects of streptozotocin-induced diabetes on lymphocyte POMC and growth hormone gene expression in the rat. Law, V., Payne, L.C., Weigent, D.A. J. Neuroimmunol. (1994) [Pubmed]
  11. Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats. De Gennaro-Colonna, V., Rossoni, G., Cocchi, D., Rigamonti, A.E., Berti, F., Muller, E.E. J. Endocrinol. (2000) [Pubmed]
  12. Expression of the growth hormone gene and the pituitary-specific transcription factor GHF-1 in diabetic rats. Bedo, G., Santisteban, P., Jolin, T., Aranda, A. Mol. Endocrinol. (1991) [Pubmed]
  13. Termination of growth hormone pulse-induced STAT5b signaling. Gebert, C.A., Park, S.H., Waxman, D.J. Mol. Endocrinol. (1999) [Pubmed]
  14. Folate malabsorption in aged rats related to low levels of pancreatic folyl conjugase. Kesavan, V., Noronha, J.M. Am. J. Clin. Nutr. (1983) [Pubmed]
  15. Estrogen stimulation of conjugase activity in the uterus of ovariectomized rats. Krumdieck, C.L., Boots, L.R., Cornwell, P.E., Butterworth, C.E. Am. J. Clin. Nutr. (1975) [Pubmed]
  16. Identification of an adenosine 3',5'-monophosphate (cAMP)-responsive region in the rat growth hormone gene: evidence for independent and synergistic effects of cAMP and thyroid hormone on gene expression. Copp, R.P., Samuels, H.H. Mol. Endocrinol. (1989) [Pubmed]
  17. The zinc finger Ikaros transcription factor regulates pituitary growth hormone and prolactin gene expression through distinct effects on chromatin accessibility. Ezzat, S., Yu, S., Asa, S.L. Mol. Endocrinol. (2005) [Pubmed]
  18. Enzymatic synthesis of folylpolyglutamates. Characterization of the reaction and its products. McGuire, J.J., Hsieh, P., Coward, J.K., Bertino, J.R. J. Biol. Chem. (1980) [Pubmed]
  19. Binding of STAT5a and STAT5b to a single element resembling a gamma-interferon-activated sequence mediates the growth hormone induction of the mouse acid-labile subunit promoter in liver cells. Ooi, G.T., Hurst, K.R., Poy, M.N., Rechler, M.M., Boisclair, Y.R. Mol. Endocrinol. (1998) [Pubmed]
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