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Ryo Morimoto
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Fumitoshi Satoh
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Osamu Murakami
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Takuo Hirose Division of Nephrology, Department of Clinical Pharmacology and Therapeutics, Department of Urology, Department of Pathology and Histotechnology, Department of Pathology, Department of Endocrinology and Applied Medical Science, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan

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Kazuhito Totsune Division of Nephrology, Department of Clinical Pharmacology and Therapeutics, Department of Urology, Department of Pathology and Histotechnology, Department of Pathology, Department of Endocrinology and Applied Medical Science, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan

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Yutaka Imai Division of Nephrology, Department of Clinical Pharmacology and Therapeutics, Department of Urology, Department of Pathology and Histotechnology, Department of Pathology, Department of Endocrinology and Applied Medical Science, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan

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Yoichi Arai Division of Nephrology, Department of Clinical Pharmacology and Therapeutics, Department of Urology, Department of Pathology and Histotechnology, Department of Pathology, Department of Endocrinology and Applied Medical Science, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan

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Takashi Suzuki Division of Nephrology, Department of Clinical Pharmacology and Therapeutics, Department of Urology, Department of Pathology and Histotechnology, Department of Pathology, Department of Endocrinology and Applied Medical Science, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan

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Hironobu Sasano Division of Nephrology, Department of Clinical Pharmacology and Therapeutics, Department of Urology, Department of Pathology and Histotechnology, Department of Pathology, Department of Endocrinology and Applied Medical Science, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan

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Sadayoshi Ito
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Kazuhiro Takahashi Division of Nephrology, Department of Clinical Pharmacology and Therapeutics, Department of Urology, Department of Pathology and Histotechnology, Department of Pathology, Department of Endocrinology and Applied Medical Science, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan

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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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