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Multiple Forms of Immunoreactive Growth Hormone-Releasing Hormone in Human Plasma, Hypothalamus, and Tumor Tissues^*

Department of Internal Medicine, Wakayanagi Hospital (A.S., S.S.) Wakayanagi, Miyagi 989-55 Japan
the Second Department of Internal Medicine, Tohoku University School of Medicine (S.Y., K.H., Y.M., K.Y.) Sendai 980 Japan

Address all correspondence and requests for reprints to: Atsushi Sasaki, M.D., Department of Internal Medicine, Wakayanagi Hospital, 130-5 Kawakita-Furukawa, Wakayanagi, Miyagi, 989-55 Japan.

We examined the nature of GHRH in plasma of normal subjects and patients with acromegaly, hypothalamic tissue, pheochromocytoma, and GHRH-producing pancreatic tumor tissue using two RIAs of different specificity. One assay was a N-terminal assay that recognized GHRH-(l–44)-NH₂, GHRH-(1–40)-OH, and GHRH-(l–37)-OH equally, and theother was a C-terminal assay that recognized only the COOHterminal amidated sequence of GHRH-(l–44)-NH₂. GHRH immunoreactivity was detectable in all samples in both assay systems, but the ratios of C- to N-terminal activity differed. The gel filtration profiles of plasma and tumor tissue revealed one peak in (or near) the position of synthetic GHRH-(l–44)-NH₂. In contrast, two peaks were found in hypothalamic tissue; a major peak in the position of synthetic GHRH-(1–44)-NH₂ and a higher mol wt peak. Ion exchange chromatography of the immunoreactive GHRH material from gel filtration of pooled plasma from normal subjects revealed three components of immunoreactive GHRH, one major peak in the position of GHRH-(1–40)-OH and two minor peaks in the positions of GHRH-(l–44)-NH₂ and GHRH-(l–37)-OH. Two componentsof immunoreactive GHRH, a major peak in the position of GHRH-(1–44)-NH₂ and a minor peak in the position of GHRH- (1–40)-OH, were found in hypothalamic tissue and pheochromocytomas. In the two ectopic GHRH-producing pancreatic tumors, three components of immunoreactive GHRH were detected: a major peak in the position of GHRH-(1–40)-OH, a smaller peak in the position of GHRH-(l–37)-OH, and a very small peak of GHRH-(l–44)-NH₂. Synthetic GHRH-(l–44)- NH₂ was not degraded by plasma during the extraction procedures. These results suggest that 1) the measured immunoreactive GHRH concentration differs when the same samples are measured by RIAs using antisera with different specificities; 2) such differences may be due to the presence of microheterogeneity of immunoreactive GHRH; 3) the microheterogeneity of immunoreactive GHRH in plasma is different from that in the hypothalamus; and 4) the posttranslational processing of GHRH in human hypothalamus is similar to that of pheochromocytomas but different from that of ectopic GHRH-producing pancreatic tumors.

^* This work was supported by a Research Grant for Intractable Diseases from the Ministry of Health and Welfare, Japan.

Received May 18, 1988.