Ontogeny of prolyl endopeptidase, pyroglutamyl peptidase I, TRH, and its metabolites in rat pancreas.
We demonstrate that two enzymes, soluble unspecific pyroglutamyl peptidase I and prolyl endopeptidase, able to degrade thyrotropin-releasing hormone (TRH) in vitro were present in pancreas at the early stage of rat development. Specific particulate pyroglutamyl peptidase II remained undetectable during ontogenesis. Pyroglutamyl peptidase I specific activity increased until day 3 and decreased after day 5. Furthermore, prolyl endopeptidase specific activity rose slightly to a peak on postnatal day 20. A good correlation between immunoreactive TRH and deaminated TRH (TRH-OH) was found in the 1st wk after birth. However, His-Pro diketopiperazine (DKP) levels were stable and low during development. We show that hot acidic extraction conditions could artefactually generate His-Pro DKP. In vivo, active site-directed inhibitors of pyroglutamyl peptidase I and prolyl endopeptidase enzymes do not show any TRH-deamidating and/or pyroglutamyl peptidase I pathways in neonatal rat pancreas. The data suggest that these two enzymes are not involved in intra- or extracellular control of TRH levels in neonatal rat pancreas and that pancreatic TRH content appears to be principally regulated by biosynthetic steps. Nevertheless, low levels of endogenous His-Pro DKP and TRH-OH identified in neonatal rat pancreas suggest that TRH or TRH-like peptides may be metabolized in this tissue in intact rats, albeit at low rates.
Laboratoire de Neuroendocrinologie Experimentale, Institut National de la Santé et de la Recherche Médicale U297, Faculté de Médecine Nord, Marseille, France.
P
P
Salers
L H
LH
Ouafik
P
P
Giraud
J Y
JY
Maltese
A
A
Dutour
C
C
Oliver
D000375:Aging; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D000085822:Prolyl Oligopeptidases; D011480:Protease Inhibitors / Q000494:pharmacology; D011751:Pyroglutamyl-Peptidase I / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012697:Serine Endopeptidases; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D011480:Protease Inhibitors; D013973:Thyrotropin-Releasing Hormone; D010450:Endopeptidases; D011751:Pyroglutamyl-Peptidase I; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases