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

• Finally, transient transfection of COS-7 cells with this cDNA led to the expression of an active ectopeptidase that displayed the characteristics of the TRH-degrading ectoenzyme [2].
• Pyroglutamyl peptidase II (PPII), a highly specific membrane-bound omegapeptidase, removes N-terminal pyroglutamyl from thyrotropin-releasing hormone (<Glu-His-Pro-NH(2)), inactivating the peptide in the extracellular space [3].
• In contrast, PAP II, following activation with trypsin or pancreatic juice, does not form insoluble structures and is rapidly digested by pancreatic proteases [4].
• Regulation of the adenohypophyseal thyrotropin-releasing hormone-degrading ectoenzyme by estradiol [5].
• Thyroid hormones rapidly and stringently regulate the messenger RNA levels of the thyrotropin-releasing hormone (TRH) receptor and the TRH-degrading ectoenzyme [6].

Biological context of Trhde

• Analysis of the thyrotropin-releasing hormone-degrading ectoenzyme by site-directed mutagenesis of cysteine residues. Cys68 is involved in disulfide-linked dimerization [7].
• Fragment analysis of the serum TRH-DE revealed that the peptide sequences correspond to the cDNA deduced amino-acid sequences of the membrane-bound brain TRH-DE, whereby two peptides were identified that are encoded by exon 1 [8].
• We also isolated a PAP II genomic DNA fragment which was characterized over 2.7 kb of gene sequence and 1.9 kb of 5' flanking sequence [1].
• The PAP II coding sequence spanned six exons separated by five introns [1].
• Pyroglutamyl peptidase II adenohypophyseal activity was not modified during lactation but changed during estrous cycle [9].

Anatomical context of Trhde

• With hepatocytes cultured in a sandwich configuration, release of the TRH-DE into the culture medium could also be demonstrated [8].
• We describe here the effects of thyroid hormones on the transcript levels of the TRH receptor, the TRH-degrading ectoenzyme, and TSH in rat pituitary, as revealed by Northern blot analysis [6].
• In the spinal cord, TRH-DE mRNA positive neurons were present in all layers [10].
• In the diencephalon, the highest TRH-DE mRNA levels were observed in the medial habenulae followed by several hypothalamic subregions [10].
• After succeeding in cloning the cDNA of TRH-DE we now report on the cellular distribution pattern of this enzyme in rat brain, spinal cord and pituitary gland using in situ hybridization histochemistry [10].

Associations of Trhde with chemical compounds

• Thyrotropin-releasing hormone-degrading ectoenzyme is a member of the M1 family of Zn-dependent aminopeptidases and catalyzes the degradation of thyrotropin-releasing hormone (TRH; Glp-His-Pro-NH2) [7].
• To investigate the functional role of these cysteines in TRH-DE we used a site-directed mutagenesis approach and replaced individually each cysteine by a serine residue [7].
• The effect of treatment with L-3,5,3'-triiodothyronine (T3) on the levels of pyroglutamyl peptidase I and pyroglutamyl peptidase II in rat brain regions, pituitary, and serum was studied [11].
• Reports of a thyrotropin-releasing hormone-degrading enzyme with narrow specificity that cleaves the pGlu-His bond of this tripeptide led us to develop a coupled assay using pGlu-His-Pro-2NA as the substrate to measure this activity [12].
• These results strongly indicate that the identity of the low-affinity, [3H]TRH-labelled site is the membrane-bound enzyme, TRH-degrading ectoenzyme, not a subpopulation of TRH receptors [13].

Physical interactions of Trhde

• Pyroglutamyl peptidase II (EC 3.4.19-) is a highly specific membrane-bound thyrotropin releasing hormone (TRH) degrading enzyme [14].

Regulatory relationships of Trhde

• Thyrotropin-releasing hormone downregulates pyroglutamyl peptidase II activity in adenohypophyseal cells [15].

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].

References