Disease relevance of Cga

• Effects of a lytic peptide conjugated to beta HCG on ovarian cancer: studies in vitro and in vivo [1].
• The GPHalpha upstream ARS was cloned in both orientations in positions upstream and downstream from the bacterial CAT gene under control of the herpes simplex virus thymidine kinase (tk) promoter [2].
• 2 IU HCG/10 g body weight were administered intraperitoneally to male mice at 1, 20, 30, 40, 60 and 90 days of age [3].

High impact information on Cga

• Sequences that flanked the transgenic integration site were cloned and mapped to mouse chromosome 4, between the Tsha and Hxb loci [4].
• We have constructed and cloned in bacteria recombinant DNA molecules containing DNA sequences coding for the precursor of the alpha subunit of thyrotropin (pre-TSH-alpha) [5].
• The amino acid sequence of the pre-TSH-alpha deduced from the nucleotide sequence showed a NH2-terminal leader sequence of 24 amino acids followed by the 96-amino-acid sequence of the apoprotein of TSH-alpha [5].
• To define this role, we have expressed Cre recombinase driven by the promoter region of the common alpha subunit of glycoprotein hormones (alpha GSU), thereby inactivating a loxP-modified SF1 locus in the anterior pituitary gland [6].
• In the alphaSU-null mice there were decreased levels of SKP 2 and elevated levels of Grb 2 expression by Western blot analysis [7].

Biological context of Cga

• Mouse Gem maps to the proximal region of chromosome 4 between Mos and Cga [8].
• The nucleotide sequences of two cDNAs (510 and 480 base pairs) were determined with chemical methods and corresponded to much of the region coding for the alpha subunit and the 3' untranslated region of pre-TSH-alpha mRNA [5].
• These data place FOXL2 in the hierarchy of pituitary developmental control and suggest a role in regulation of Cga gene expression [9].
• Six species were obtained from TSH alpha (with two glycosylation sites), including neutral oligosaccharides as well as those with one or two negative charges [10].
• The P-Lim DNA binding site on the glycoprotein hormone alpha subunit (alpha-GSU) gene promoter is conserved in mammals [11].

Anatomical context of Cga

• Spleen cells from Balb/c mice immunized with HCG were subjected to the normal hybridoma procedures [12].
• The injection of HCG (1 IU/day) or LH releasing hormone (0.1 or 0.4 microgram/6h) for 1 or 2 days resulted in significant and marked increases on day 18 in testicular and serum androgen levels and/or the proliferation of seminal vesicle cells measured with 5-[125I]iodo-2'-deoxyuridine uptake by the whole seminal vesicles [13].
• Using a 4.6 kb promoter from the mouse glycoprotein hormone alpha-subunit (alphaGSU or Cga) gene, we have generated and characterized a line of transgenic mice that express cre recombinase in the anterior and intermediate lobes of the pituitary gland [14].
• Regulation of the glycoprotein hormone alpha-subunit (GPHalpha) gene has been studied extensively in pituitary and placental cell lines, but little is known of the transcriptional regulators important for its ectopic expression [15].
• Positive signal for alpha-SU was found in the majority of renal peritubular fibroblasts in the cortex and outer medulla, and in Ito cells [16].

Associations of Cga with chemical compounds

• These data were corroborated by assessing plasma levels of the respective peptide and steroid hormones. alphaERKO and alphabetaERKO females exhibited increased pituitary Cga and Lhb expression and increased plasma LH levels, whereas both were normal in betaERKO [17].
• In all three tissue types, units with 9 Man tended to accumulate in TSH beta-subunits, whereas Man-trimming from Man9GlcNAc to Man8GlcNAc proceeded more rapidly in TSH alpha-subunits, and in free alpha-subunits [18].
• In secreted TSH dimer, TSH beta incorporated 1.3 times more [35S]sulfate (P less than 0.05) and 2.5 times more [3H] N-acetylmannosamine (P less than 0.02) per carbohydrate chain than did TSH alpha [19].
• Each of the three secreted subunits (TSH alpha, TSH beta, and free alpha) incorporated both sulfate and sialic acid [19].
• Dexamethasone failed to stimulate the effect of HCG [20].

Other interactions of Cga

• The first pituitary transcripts detected are from alpha GSU, which encodes the alpha-subunit common to the gonadotropins (FSH and LH) and TSH [21].
• 5. Thyroid-stimulating hormone-beta (TSH beta) subunit mRNA was expressed initially in both the pas tuberalis and ventromedial pars distalis on Day E14.5, with an identical spatial distribution to alpha-GSU at the time [22].
• The effects of ACTH and dexamethasone on the uterine weight of immature mice treated with HCG or oestradiol-17 beta were studied [20].

Analytical, diagnostic and therapeutic context of Cga

• The resulting MCA's (from 78 clones) were evaluated in radioimmunoassay, haemagglutination and enzyme immunoassay with whole HCG [12].
• CONCLUSIONS: Passive immunization with recombinant HCG-specific antibodies may have clinical utility as (i) diagnostic and therapeutic tools for HCG-expressing cancers and (ii) contraceptive measures [23].

References