Catabolism of Thyroliberin by Rat Adenohypophyseal Tissue Extract

Abstract

Rapid fragmentation of thyroliberin (< Glu‐His‐Pro‐NH₂) by rat adenohypophyseal tissue enzymes could be demonstrated. Based on the identification of the metabolic products and by the demonstration that the individual enzymatic reactions can be preferentially blocked by enzyme inhibitors, specific and sensitive biochemical tests could be developed in order to monitor the enzymatic activities after gel chromatographic fractionation of the tissue extracts. These findings are in agreement with the interpretation that the observed degradation of thyroliberin by hypophyseal tissue extracts may follow the proposed pathways. The primary enzymatic cleavage of thyroliberin is either initiated by the action of a ‘thyroliberin‐deamidating enzyme’ (thyroliberin → < Glu‐His‐Pro‐OH → NH₃), or by the action of a pyroglutamate aminopeptidase (thyroliberin → 2). While the pyroglutamate aminopeptidase also catayzes the subsequent degradation of deamidated thyroliberin (2 is not catalyzed by the ‘thyroliberin‐deamidating enzyme’ but by a post‐proline dipeptidyl aminopeptidase. Hydrolysis of the common intermediary metabolite His‐Pro‐OH to the free amino acids is apparently catalyzed by a proline dipeptidase. In addition to these enzymatic events rapid cyclization of His‐Pro‐NH₂ to histidyl‐proline‐diketopiperazine () could be observed. This reaction however is mainly due to the non‐enzymatic intramolecular condensation reaction which is characteristic for proline‐containing dipeptide derivatives. An enzymatic activity which catalyzes this reaction could not be observed when the enzyme fractions were tested. Enzymatic degradation of , by hypophyseal tissue extracts could also not be observed.