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Journal of Endocrinology (2008) 198, 175-183    DOI: 10.1677/JOE-08-0103
© 2008 Society for Endocrinology

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Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues

Ryo Morimoto, Fumitoshi Satoh, Osamu Murakami, Takuo Hirose1, Kazuhito Totsune1, Yutaka Imai1, Yoichi Arai2, Takashi Suzuki3, Hironobu Sasano4, Sadayoshi Ito and Kazuhiro Takahashi5

Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan1 Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine, Sendai, Miyagi 980-8574, Japan2 Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan3 Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan4 Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan5 Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan

(Correspondence should be addressed to K Takahashi; Email: ktaka-md{at}mail.tains.tohoku.ac.jp)

Adrenomedullin 2/intermedin (AM2/IMD) is a new member of calcitonin/calcitonin gene-related peptide family. AM is expressed in various tumors including adrenocortical tumors and modulates tumor growth. The AM2/IMD expression has not been studied, however, in adrenal tumors. The expression of AM2/IMD and AM was therefore studied in human adrenal tumors and attached non-neoplastic adrenal tissues by immunocytochemistry (ICC). Immunoreactive (IR)–AM2/IMD was measured by RIA. Furthermore, the expression of AM2/IMD and its receptor components, calcitonin receptor-like receptor (CRLR), and receptor activity-modifying proteins (RAMPs) 1, 2, and 3 mRNA in these tissues was studied by reverse transcription PCR (RT-PCR). ICC showed that AM2/IMD and AM immunoreactivities were localized in adrenocortical tumors and pheochromocytomas. AM2/IMD and AM immunoreactivities were detected in medulla of attached non-neoplastic tissues, while the degree of immunoreactivity for AM2/IMD and AM in cortices of attached adrenals was relatively weak or undetectable. RIA detected IR-AM2/IMD in adrenal tumors (0.414±0.12 to 0.786±0.27 pmol/g wet weight, mean±S.E.M.) and attached adrenal tissues (0.397±0.052 pmol/g wet weight). Reverse-phase high-performance liquid chromatography showed one broad peak eluted in the similar position to synthetic AM2/IMD with several minor peaks. RT-PCR showed expression of AM2/IMD, CRLR, and RAMP1, RAMP2, and RAMP3 mRNA in tissues of adrenal tumors and attached adrenal glands. In conclusion, AM2/IMD is expressed in human adrenal tumors and attached non-neoplastic adrenal tissues and may play (patho-)physiological roles in normal and neoplastic adrenals as an autocrine/paracrine regulator.







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