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,
GERNOT WOLFRAM,
JURAJ MOJTO,
JOCHEN SCHOPOHL,
YURIKO SPIESS,
RUDOLF HUBER,
O. ALBRECHT MÜLLER and
KLAUS VON WERDER
Medizinische Klinik Innenstadt, University of Munich Munich, West Germany
Address all correspondence and requests for reprints to: Dr. Klaus von Werder, Schlosspark Klinik, Heubnerweg 2, 1000 Berlin 19, West Germany.
The distribution and physical and biological properties of GH-releasing hormone-like immunoreactivity (GHRH-IR) in human tissues and tumors was investigated using a specific GHRH RIA, gel chromatography, immunoaffinity chromatography, and bioassay with cultured rat anterior pituitary cells. Variable concentrations of GHRH-IR, ranging from 1.4–39.0 ng/g wet wt, were found in normal liver, lung, placenta, and pancreas. In the latter tissue, however, a different chromatographic profile and a marked decrease in GHRH-IR after immunoaffinity occurred, suggesting that GHRH-IR in pancreatic extracts is not native GHRH. In all tumors examined (n = 35) GHRH-IR could be detected, and four tumors (three carcinoids and one jejunal carcinoma) contained a very high amount of GHRH-IR (>1000 ng/g wet wt). Affinity chromatography of tumor extracts led to a significant loss (>50%) of GHRH-IR in nine tumors. The four tumors containing large amounts of GHRH-IR were obtained from two patients with active acromegaly and two patients who had no clinical evidence of acromegaly. Using antibodies with different specificities for GHRH-(l–44) and GHRH shortened at the C-terminus, varying concentrations of GHRH-(1–44) in these tumors were found, ranging from 10–87% of the total GHRH-IR. The biological activity of GHRH in the four tumor extracts was similar to that of synthetic GHRH alone or GHRH added to control tissue subjected to extraction. These results demonstrate the presence of GHRH-IR in the majority of normal tissues and tumors, which, though they may produce large amounts of biologically active GHRH, do not always lead to acromegaly.
* This work was supported by the Deutsche Forschungsgemeinschaft (WE 439/5–2).
Present address: Istituto di Neurochirurgia, Universita di Milano, Milan, Italy.
Received March 14, 1989.
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