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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0103v1 198/1/175    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Morimoto, R. Articles by Takahashi, K. Search for Related Content PubMed PubMed Citation Articles by Morimoto, R. Articles by Takahashi, K.

R Morimoto, Department of Medicine, Division of Nephrology, Endocrinology and vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
F Sato, Department of Medicine, Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi-980-8574, Japan
O Murakami, Department of Medicine, Division of Nephrology, Endocrinology and Vascular Medicine, Tohoke University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
T Hirose, Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine, Sendai, Miyagi 980-8574, Japan
K Totsune, Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine, Sendai, Miyagi 980-8574, Japan
Y Imai, Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine, Sendai, Miyagi - 980-8574, Japan
Y Arai, Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
T Suzuki, Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Miyagi-980-8574, Japan
H Sasano, Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
S Ito, Department of Medicine, Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi-980-8574, Japan
K Takahashi, Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan

Correspondence: Ryo Morimoto, Email: rmorimoto{at}mail.tains.tohoku.ac.jp

Abstract

Adrenomedullin 2/intermedin (AM2/IMD) is a new member of calcitonin/calcitonin gene-related peptide family. Adrenomedullin (AM) is expressed in various tumors including adrenocortical tumors and modulates tumor growth. AM2/IMD expression has not been studied, however, in adrenal tumors. Expression of AM2/IMD and AM was therefore studied in human adrenal tumors and attached non-neoplastic adrenal tissues by immunocytochemistry. Immunoreactive (IR) -AM2/IMD was measured by radioimmunoassay. Furthermore, the expression of AM2/IMD and its receptor components, calcitonin receptor-like receptor (CRLR), and receptor activity modifying protein (RAMP) 1, 2, and 3 mRNA in these tissues was studied by reverse-transcription polymerase chain reaction (RT-PCR). Immunocytochemistry showed AM2/IMD and AM immunoreactivity was localized in adrenocortical tumors and pheochromocytomas. AM2/IMD and AM immunoreactivity was 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. Radioimmunoassay 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 HPLC 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, 2, and 3 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.