This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via Google Scholar Google Scholar Articles by TAKAHARA, Y. Articles by PETERKOFSKY, A. Search for Related Content PubMed PubMed Citation Articles by TAKAHARA, Y. Articles by PETERKOFSKY, A.

Detection in Human Serum by Radioimmunoassay of Histidyl-Proline Diketopiperazine, a Metabolite of Thyrotropin-Releasing Hormone

YOSHIYUKI TAKAHARA^*, FIORENZO BATTAINI, DOUGLAS D. ROSS, STEVEN A. AKMAN, NICHOLAS R. BACHUR, KENT R. BAILEY, EDWARD LAKATOS and ALAN PETERKOFSKY

Laboratory of Biochemical Genetics, National Heart, Lung, and Blood Institute Bethesda, Maryland 20205

Address all correspondence and requests for reprints to: Dr. Alan Peterkofsky, National Institutes of Health, Building 36, Room 4C-11, Bethesda, Maryland 20205.

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 a 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.

^* Permanent address: Central Research Laboratories, Ajinomoto Co., Inc. Kawasaki, Japan.

Permanent address: Institute of Pharmacology, University of Milan, Milan, Italy.

Laboratory of Clinical Biochemistry, Baltimore Cancer Research Program, DCT, NCI, NIH, 655 West Baltimore Street, Baltimore, Maryland 21201.

Mathematics and Applied Statistics Branch, National Heart, Lung, and Blood Institute.

Received April 16, 1982.