choroid plexus carcinoma cells (7) and by cultured glioblastoma cells (8). It is known that ectopic ACTH- secreting tumors produce and secrete not only ACTH.
European Journal of Endocrinology (1998) 138 436–439
ISSN 0804-4643
SHORT COMMUNICATION
Expression of adrenomedullin and adrenomedullin mRNA in ectopic ACTH-secreting tumors Osamu Murakami1, Kazuhiro Takahashi2, Fumitoshi Satoh1, Kazuhito Totsune1, Masahiko Sone2,4, Zenei Arihara1, Noriaki Andoh3 and Toraichi Mouri5 1
Second Department of Internal Medicine, 2Department of Molecular Biology and 3Department of Pathology, Tohoku University School of Medicine, Sendai, Miyagi 980–77, Japan, 4Department of Internal Medicine, the National Iwate Hospital, Ichinoseki, Iwate 021, Japan, and 5Division of Neuroendocrinology, Mouri Clinic, Natori, Miyagi 981–12, Japan (Correspondence should be addressed to K Takahashi, Department of Molecular Biology, Tohoku University School of Medicine, 2–1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980–8575, Japan)
Abstract Objective: To study the expression of adrenomedullin, a potent vasodilator peptide originally isolated from a pheochromocytoma, in ectopic ACTH-secreting tumors. Methods: Tumor tissue concentrations of adrenomedullin, calcitonin gene-related peptide, neuropeptide Y, endothelin-1, corticotropin-releasing hormone and ACTH were measured in three ectopic ACTH-secreting tumors by RIA. The expression of adrenomedullin mRNA was examined by northern blot analysis of tissue from one of the tumors. Results: Immunoreactive adrenomedullin was detected in tumor tissues of three ectopic ACTHsecreting tumors (0.60–18.5 pmol/g wet weight). Calcitonin gene-related peptide, neuropeptide Y, endothelin-1 and corticotropin-releasing hormone were also detected in the tumor tissues. The tumor tissue concentrations of immunoreactive adrenomedullin were comparable to those of these four peptides, but much lower than those of ACTH. Northern blot analysis showed the expression of adrenomedullin mRNA in one tumor from which sufficient tissue was available for such study. The plasma concentration of immunoreactive adrenomedullin was increased in one patient (41.3 pmol/l, control 13.5 6 3.6 pmol/l, mean 6 S.D., n ¼ 12). Conclusions: These results suggest that adrenomedullin is produced by ectopic ACTH-secreting tumors, together with other neuropeptides, and raise the possibility that adrenomedullin is related to the pathophysiology of these tumors. European Journal of Endocrinology 138 436–439
Introduction Adrenomedullin (ADM) is a potent vasodilator peptide that was originally isolated from human pheochromocytoma (1). The C-terminal portion (16–52) of ADM has about 27% homology with calcitonin gene-related peptide (CGRP). ADM has been shown to regulate the production and secretion of some hormones, such as ACTH (2) and aldosterone (3, 4), and to modulate the proliferation and differentiation of cells (5). ADM mRNA and ADM receptor mRNA are expressed in various kinds of tumors, including pulmonary tumors (6). ADM is produced and secreted by cultured choroid plexus carcinoma cells (7) and by cultured glioblastoma cells (8). It is known that ectopic ACTHsecreting tumors produce and secrete not only ACTH but also other peptides, such as calcitonin. We reported the presence of immunoreactive (IR)-endothelin, IRneuropeptide Y (NPY), and IR-corticotropin-releasing q 1998 Society of the European Journal of Endocrinology
hormone (CRH) in the tumor tissue of an ectopic ACTHsecreting bronchial carcinoid tumor (9). There is no information on ADM in ectopic ACTH-secreting tumors. We therefore studied the expression of ADM and ADM mRNA in tumor tissue of ectopic ACTH-secreting tumors.
Materials and methods Samples Tumor tissues were obtained at surgery from three patients with ectopic ACTH-secreting tumors (Table 1a). Tumor tissues were stored at ¹80 8C until required for the extraction of peptides and RNA. All the patients had increased plasma concentrations of ACTH and cortisol (Table 1a). After surgery, plasma concentrations of ACTH and cortisol were decreased and patients 1 and 3
Adrenomedullin in ectopic ACTH-secreting tumors
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Table 1 Clinical characteristics and results of analyses of plasma IR-ADM concentrations and tumor tissue concentrations of IR-ADM, ACTH and four other peptides in three patients with ectopic ACTH- secreting tumors.
a Clinical characteristics
Sex
Plasma ACTH (pmol/l)
Plasma cortisol (nmol/l)
Plasma aldosterone (pmol/l)
Serum Kþ (pmol/l)
58
F
18.1
847
