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Gene Review

Trhde  -  thyrotropin-releasing hormone degrading...

Rattus norvegicus

Synonyms: PAP-II, Pyroglutamyl-peptidase II, TRH-DE, TRH-degrading ectoenzyme, TRH-specific aminopeptidase, ...
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Disease relevance of Trhde

  • Studies on gene expression demonstrated that PAP II mRNA concentration increased within 6 h following induction of pancreatitis, reached maximal levels (> 200 times control values) at 24-48 h, and decreased thereafter, similar to PAP I [1].

High impact information on Trhde


Biological context of Trhde


Anatomical context of Trhde


Associations of Trhde with chemical compounds


Physical interactions of Trhde


Regulatory relationships of Trhde


Other interactions of Trhde

  • Previous biochemical studies have indicated that the membrane-bound thyrotropin-releasing hormone (TRH)-degrading enzyme (TRH-DE) from brain and liver and the serum TRH-DE are derived from the same gene [8].
  • CONCLUSION: It is considered that the elongated mRNA affects the function of PAP II/Reg III protein because the elongated mRNA with long 3; untranslated regions is known to be involved in the translation efficiency [16].
  • RESULTS: Analysis of the open reading frame of the cDNA indicated that the deduced protein from the messenger RNA (mRNA) was a polypeptide of 174 amino acids, unexpectedly similar to that of a known gene, rat pancreatitis-associated protein II/regenerating gene III (PAP II/Reg III) [16].
  • In the intestinal tract, where PAP II is not expressed, the pattern of PAP III expression was comparable with that of PAP I; fasting induced a decrease in its mRNA concentration by more than 80%, which could be reversed within 6 h upon feeding [17].
  • Delineation of a particulate thyrotropin-releasing hormone-degrading enzyme in rat brain by the use of specific inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase [12].

Analytical, diagnostic and therapeutic context of Trhde

  • As indicated by sequence alignment, TRH-DE and the other members of the M1 family of aminopeptidases have a distinct set of conserved amino acid residues in common [18].
  • Antibodies raised to a synthetic peptide of PAP II detected a single band in Western blot analysis of the pancreatic secretory proteins from rats with pancreatitis, with a M(r) compatible with the theoretical M(r) of PAP II.(ABSTRACT TRUNCATED AT 250 WORDS)[1]
  • After treatment with triiodothyronine (T3) a dramatic increase in the mRNA levels of the TRH-DE and a decrease in the intensity of the TRH receptor could be observed in the anterior lobe of the pituitary [10].


  1. Identification of a second rat pancreatitis-associated protein. Messenger RNA cloning, gene structure, and expression during acute pancreatitis. Frigerio, J.M., Dusetti, N.J., Keim, V., Dagorn, J.C., Iovanna, J.L. Biochemistry (1993) [Pubmed]
  2. Cloning of a cDNA encoding an ectoenzyme that degrades thyrotropin-releasing hormone. Schauder, B., Schomburg, L., Köhrle, J., Bauer, K. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  3. Homology modeling and site-directed mutagenesis of pyroglutamyl peptidase II. Insights into omega-versus aminopeptidase specificity in the M1 family. Chávez-Gutiérrez, L., Matta-Camacho, E., Osuna, J., Horjales, E., Joseph-Bravo, P., Maigret, B., Charli, J.L. J. Biol. Chem. (2006) [Pubmed]
  4. A family of 16-kDa pancreatic secretory stress proteins form highly organized fibrillar structures upon tryptic activation. Graf, R., Schiesser, M., Scheele, G.A., Marquardt, K., Frick, T.W., Ammann, R.W., Bimmler, D. J. Biol. Chem. (2001) [Pubmed]
  5. Regulation of the adenohypophyseal thyrotropin-releasing hormone-degrading ectoenzyme by estradiol. Schomburg, L., Bauer, K. Endocrinology (1997) [Pubmed]
  6. Thyroid hormones rapidly and stringently regulate the messenger RNA levels of the thyrotropin-releasing hormone (TRH) receptor and the TRH-degrading ectoenzyme. Schomburg, L., Bauer, K. Endocrinology (1995) [Pubmed]
  7. Analysis of the thyrotropin-releasing hormone-degrading ectoenzyme by site-directed mutagenesis of cysteine residues. Cys68 is involved in disulfide-linked dimerization. Papadopoulos, T., Heuer, H., Bauer, K. Eur. J. Biochem. (2000) [Pubmed]
  8. Purification and characterization of the thyrotropin-releasing hormone (TRH)-degrading serum enzyme and its identification as a product of liver origin. Schmitmeier, S., Thole, H., Bader, A., Bauer, K. Eur. J. Biochem. (2002) [Pubmed]
  9. Some events of thyrotropin-releasing hormone metabolism are regulated in lactating and cycling rats. Uribe, R.M., Joseph-Bravo, P., Pasten, J., Ponce, G., Méndez, M., Covarrubias, L., Charli, J.L. Neuroendocrinology (1991) [Pubmed]
  10. Region-specific expression of thyrotrophin-releasing hormone-degrading ectoenzyme in the rat central nervous system and pituitary gland. Heuer, H., Ehrchen, J., Bauer, K., Schäfer, M.K. Eur. J. Neurosci. (1998) [Pubmed]
  11. Regulation of thyrotropin releasing hormone degrading enzymes in rat brain and pituitary by L-3,5,3'-triiodothyronine. Suen, C.S., Wilk, S. J. Neurochem. (1989) [Pubmed]
  12. Delineation of a particulate thyrotropin-releasing hormone-degrading enzyme in rat brain by the use of specific inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase. Friedman, T.C., Wilk, S. J. Neurochem. (1986) [Pubmed]
  13. Pharmacologically distinct binding sites in rat brain for [3H]thyrotropin-releasing hormone (TRH) and [3H][3-methyl-histidine(2)]TRH. Kelly, J.A., Slator, G.R., O'Boyle, K.M. Biochem. Pharmacol. (2002) [Pubmed]
  14. Pyroglutamyl peptidase II inhibition specifically increases recovery of TRH released from rat brain slices. Charli, J.L., Mendez, M., Vargas, M.A., Cisneros, M., Assai, M., Joseph-Bravo, P., Wilk, S. Neuropeptides (1989) [Pubmed]
  15. Thyrotropin-releasing hormone downregulates pyroglutamyl peptidase II activity in adenohypophyseal cells. Vargas, M.A., Joseph-Bravo, P., Charli, J.L. Neuroendocrinology (1994) [Pubmed]
  16. The elongated PAP II/Reg III mRNA is upregulated in rat pancreas during acute experimental pancreatitis. Honda, H., Nakamura, H., Otsuki, M. Pancreas (2002) [Pubmed]
  17. Cloning, expression and chromosomal localization of the rat pancreatitis-associated protein III gene. Dusetti, N.J., Frigerio, J.M., Szpirer, C., Dagorn, J.C., Iovanna, J.L. Biochem. J. (1995) [Pubmed]
  18. Mutational analysis of the thyrotropin-releasing hormone-degrading ectoenzyme. similarities and differences with other members of the M1 family of aminopeptidases and thermolysin. Papadopoulos, T., Kelly, J.A., Bauer, K. Biochemistry (2001) [Pubmed]
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