Detection in human serum by radioimmunoassay of histidyl-proline diketopiperazine, a metabolite of thyrotropin-releasing hormone.
Cyclo(His-Pro) is believed to be a metabolite of TRH. A specific antiserum directed against cyclo(His-Pro) was used to detect immunoreactive material in human serum. Gel filtration column chromatography was used to establish that cyclo(His-Pro)-like immunoreactivity was found not only in free form established to be identical to cyclo(His-Pro) by high pressure liquid chromatography analysis on reverse phase and cation exchange columns, but also in a fraction of about 100,000 mol wt. Free cyclo(His-Pro) was released by heating column fractions of 70,000 mol wt that were not immunoreactive before heating. A procedure for estimation of the content of free cyclo(His-Pro) in human serum was developed. Normal levels of cyclo(His-Pro) determined by this procedure were in the range of 11-33 pmol/ml. The level of cyclo(His-Pro) in sera of individuals with hypothyroidism, hyperthyroidism, or alcoholic cirrhosis was in the normal range, while patients with renal failure had approximately 3-fold elevated levels of the peptide. Analysis of human sera drawn at 3-h intervals over a 24-h period suggested a circadian rhythm of cyclo(His-Pro) levels.
D000818:Animals; D001923:Brain Chemistry; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002940:Circadian Rhythm; D006358:Hot Temperature; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood; D007037:Hypothyroidism / Q000097:blood; D007674:Kidney Diseases / Q000097:blood; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood; D008297:Male; D010456:Peptides, Cyclic / Q000032:analysis / Q000097:blood*; D010879:Piperazines / Q000032:analysis / Q000097:blood*; D011863:Radioimmunoassay; D051381:Rats; D012016:Reference Values; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D010456:Peptides, Cyclic; D010879:Piperazines; D013973:Thyrotropin-Releasing Hormone; C015924:histidyl-proline diketopiperazine