Demonstration of pyroglutamylpeptidase and amidase activities toward thyrotropin-releasing hormone in hamster hypothalamus extracts.
Using a radioimmunoassay method for thyrotropin-releasing hormone, the presence of thyrotropin-releasing hormone-metabolizing activity in various hamster tissues was demonstrated. While there was substantial activity degrading thyrotropin-releasing hormone in hypothalamus, there was a notable absence of such activity in pituitary. The enzymatic activity in the hypothalamus was shown to be soluble and separable into two fractions. Analysis of the metabolic products formed by the two enzymes indicated that one possessed an amidase activity (less than Glu-His-Pro-NH2 leads to less than Glu-His-Pro) and the other possessed pyroglutamylpeptidase activity (less than Glu-His-Pro-NH2 leads to less than Glu+His-Pro-NH2). Other peptides containing NH2-terminal pyroglutamic acid or COOH-terminal amide groups did not block the hydrolysis of thyrotropin-releasing hormone, suggesting that the enzymes were specific. Some inhibitors preferentially blocked the activity of one or the other enzymes. Of possible biological significance is the observation that thyroid-stimulating hormone inhibited the amidase activity while hydrocortisone inhibited the pyroglutamylpeptidase activity.
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D006224:Cricetinae; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology*; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D010447:Peptide Hydrolases / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology; D013972:Thyrotropin / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism
D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D010447:Peptide Hydrolases; D000581:Amidohydrolases; D006854:Hydrocortisone