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.
Salers
P
P
Laboratoire de Neuroendocrinologie Experimentale, Institut National de la Santé et de la Recherche Médicale U297, Faculté de Médecine Nord, Marseille, France.
Ouafik
L H
LH
Giraud
P
P
Maltese
J Y
JY
Dutour
A
A
Oliver
C
C
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