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

• The deduced amino acid sequence of human gamma-glutamyl hydrolase shows 67% identity to that of rat gamma-glutamyl hydrolase [6].
• A cDNA encoding human gamma-glutamyl hydrolase has been identified by searching an expressed sequence tag data base and using rat gamma-glutamyl hydrolase cDNA as the query sequence [6].
• A complete cDNA sequence of gamma-glutamyl hydrolase was obtained using degenerate oligonucleotides derived from peptide sequences, screening of a rat hepatoma cDNA library, and reverse transcription polymerase chain reaction [1].
• Estrogens inhibit tumor growth and modify PRL and GH expression in the MtT/W15 transplantable rat pituitary tumor [7].
• The effects of estradiol (E2) and diethylstilbestrol (DES) on PRL and GH mRNA levels were investigated [7].

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

• Based upon the deduced amino acid sequence the peptide component of gamma-glutamyl hydrolase had a molecular weight of 33,400 [1].
• Taken together, the findings indicate that DNA methylation modulates but does not control GH gene expression [8].
• The S-phase-associated augmentation in GH production did not appear to result from a decrease in ADP-ribosylation induced by 2 mM thymidine treatment which was utilized for the S-phase synchronization [2].
• Our studies show further that the decrease in [3H]uridine incorporation into GH mRNA did not result from a cell cycle specific change in efficiency of hybridization or exclusively to an S-phase associated increased rate of degradation of GH mRNA [2].
• These studies revealed that the two GH Pit-1 binding sites are necessary, but not sufficient, for efficient transcriptional activation [3].

Anatomical context of Ggh

• Since diabetes produced an approximately 3-fold reduction of circulating T3, the potential role of thyroid hormones on GH gene expression was also evaluated in thyroidectomized and thyroidectomized diabetic rats [12].
• To define the quantitative contribution of the two Pit-1 response elements and the potential role of other factors in GH gene activation, we systematically assessed the ability of a series of GH promoter regions to activate transgenes in the mouse anterior pituitary gland [3].
• STAT5b is activated in liver cells in vivo by physiological pulses of GH and then is rapidly deactivated [13].
• High folyl conjugase (pteroyl gamma-glutamyl hydrolase) levels are induced in pancreas as a response to dietary folate intake; the conjugase is secreted into the gut lumen where enzyme levels rise sequentially reaching maximum in the midgut region within 30 to 60 min after folate ingestion [14].
• Estrogen stimulation of conjugase activity in the uterus of ovariectomized rats [15].

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].

References