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Presence of Kisspeptin-like Immunoreactivity in Human Adrenal Glands and Adrenal Tumors

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Abstract

Kisspeptins are neuropeptides which activate the hypothalamo-pituitary gonadal axis and are considered to play important physiological roles in the reproduction. Kisspeptins have also been reported to stimulate the aldosterone secretion from the adrenal cortex. However, the expression of kisspeptins in human adrenal glands and adrenal tumors has not been clarified yet. We, therefore, studied the presence of kisspeptin-like immunoreactivity (LI) in human adrenal glands and adrenal tumors (adrenocortical adenomas, adrenocortical carcinomas, and pheochromocytomas) by radioimmunoassay and immunocytochemistry. Kisspeptin-LI was detected in all the tissues examined; normal portions of adrenal glands (3.0 ± 2.3 pmol/g wet weight, n = 21, mean ± SD), aldosterone-producing adenomas (4.6 ± 3.3 pmol/g wet weight, n = 10), cortisol-producing adenomas (2.7 ± 1.4 pmol/g wet weight, n = 14), adrenocortical carcinomas (1.7 ± 0.2 pmol/g wet weight, n = 4), and pheochromocytomas (1.8 ± 0.8 pmol/g wet weight, n = 6). There was no significant difference in kisspeptin-LI levels among them. Immunocytochemistry showed positive kisspeptin-immunostaining in normal adrenal glands, with stronger immunostaining found in the medulla. Furthermore, positive kisspeptin-immunostaining was found in all types of adrenal tumors examined; adrenocortical adenomas, adrenocortical carcinomas, and pheochromocytomas. The intensity of kisspeptin-immunostaining in these adrenal tumors was, however, not so strong as that in normal adrenal medulla. The present study has shown for the first time the presence of kisspeptin-LI in adrenal glands and adrenal tumors.

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References

  • Adrian TE, Allen JM, Terenghi G, Bacarese-Hamilton AJ, Brown MJ, Polak JM, Bloom SR (1983) Neuropeptide Y in phaeochromocytomas and ganglioneuroblastomas. Lancet 2:540–542

    Article  CAS  PubMed  Google Scholar 

  • Bilban M, Ghaffari-Tabrizi N, Hintermann E, Bauer S, Molzer S, Zoratti C et al (2004) Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. J Cell Sci 117:1319–1328

    Article  CAS  PubMed  Google Scholar 

  • Bowe JE, King AJ, Kinsey-Jones JS, Foot VL, Li XF, O’Byrne KT et al (2009) Kisspeptin stimulation of insulin secretion: mechanisms of action in mouse islets and rats. Diabetologia 52:855–862

    Article  CAS  PubMed  Google Scholar 

  • Dhillo WS, Chaudhri OB, Patterson M, Thompson EL, Murphy KG, Badman MK et al (2005) Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab 90:6609–6615

    Article  CAS  PubMed  Google Scholar 

  • Fukuda T, Takahashi K, Suzuki T, Saruta M, Watanabe M, Nakata T, Sasano H (2005) Urocortin 1, urocortin 3/stresscopin, and corticotropin-releasing factor receptors in human adrenal and its disorders. J Clin Endocrinol Metab 90:4671–4678

    Article  CAS  PubMed  Google Scholar 

  • Gottsch ML, Cunningham MJ, Smith JT, Popa SM, Acohido BV, Crowley WF et al (2004) A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 145:4073–4077

    Article  CAS  PubMed  Google Scholar 

  • Hauge-Evans AC, Richardson CC, Milne HM, Christie MR, Persaud SJ, Jones PM (2006) A role for kisspeptin in islet function. Diabetologia 49:2131–2135

    Article  CAS  PubMed  Google Scholar 

  • Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le PE et al (2001) The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276:34631–34636

    Article  CAS  PubMed  Google Scholar 

  • Lee JH, Miele ME, Hicks DJ, Phillips KK, Trent JM, Weissman BE, Welch DR (1996) KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst 88:1731–1737

    Article  CAS  PubMed  Google Scholar 

  • Lundberg JM, Hamberger B, Schultzberg M, Hökfelt T, Granberg PO, Efendić S et al (1979) Enkephalin- and somatostatin-like immunoreactivities in human adrenal medulla and pheochromocytoma. Proc Natl Acad Sci USA 76:4079–4083

    Article  CAS  PubMed  Google Scholar 

  • Mead EJ, Maguire JJ, Kuc RE, Davenport AP (2007) Kisspeptins are novel potent vasoconstrictors in humans, with a discrete localization of their receptor, G protein-coupled receptor 54, to atherosclerosis-prone vessels. Endocrinology 148:140–147

    Article  CAS  PubMed  Google Scholar 

  • Morimoto R, Satoh F, Murakami O, Hirose T, Totsune K, Imai Y et al (2008a) Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues. J Endocrinol 198:175–183

    Article  CAS  Google Scholar 

  • Morimoto R, Satoh F, Murakami O, Suzuki T, Abe T, Tanemoto M et al (2008b) Immunohistochemistry of a proliferation marker Ki67/MIB1 in adrenocortical carcinomas: Ki67/MIB1 labeling index is a predictor for recurrence of adrenocortical carcinomas. Endocr J 55:49–55

    Article  Google Scholar 

  • Morimoto R, Satoh F, Murakami O, Totsune K, Arai Y, Suzuki T et al (2008c) Immunolocalization of urotensin II and its receptor in human adrenal tumors and attached non-neoplastic adrenal tissues. Peptides 29:873–880

    Article  CAS  Google Scholar 

  • Muir AI, Chamberlain L, Elshourbagy NA, Michalovich D, Moore DJ, Calamari A et al (2001) AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem 276:28969–28975

    Article  CAS  PubMed  Google Scholar 

  • Nakamura Y, Aoki S, Xing Y, Sasano H, Rainey WE (2007) Metastin stimulates aldosterone synthesis in human adrenal cells. Reprod Sci 14:836–845

    Article  CAS  PubMed  Google Scholar 

  • Navarro VM, Castellano JM, Fernandez-Fernandez R, Barreiro ML, Roa J, Sanchez-Criado JE et al (2004) Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide. Endocrinology 145:4565–4574

    Article  CAS  PubMed  Google Scholar 

  • Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K et al (2001) Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 411:613–617

    Article  CAS  PubMed  Google Scholar 

  • Satoh F, Takahashi K, Murakami O, Totsune K, Sone M, Ohneda M et al (1996) Immunocytochemical localization of adrenomedullin-like immunoreactivity in the human hypothalamus and the adrenal gland. Neurosci Lett 203:207–210

    Article  CAS  PubMed  Google Scholar 

  • Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK et al (2003) The GPR54 gene as a regulator of puberty. N Engl J Med 349:1614–1627

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Totsune K, Sone M, Ohneda M, Murakami O, Itoi K, Mouri T (1992) Human brain natriuretic peptide-like immunoreactivity in human brain. Peptides 13:121–123

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Yoshinoya A, Murakami O, Totsune K, Shibahara S (2000) Production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1, by cultured human adrenocortical carcinoma cells. Peptides 21:251–256

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Totsune K, Murakami O, Arihara Z, Noshiro T, Hayashi Y, Shibahara S (2003) Expression of urotensin II and its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensin II. Peptides 24:301–306

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Totsune K, Murakami O, Saruta M, Nakabayashi M, Suzuki T et al (2004) Expression of urocortin III/stresscopin in human heart and kidney. J Clin Endocrinol Metab 89:1897–1903

    Article  CAS  PubMed  Google Scholar 

  • Uenoyama Y, Tsukamura H, Maeda KI (2009) Kisspeptin/metastin: a key molecule controlling two modes of gonadotrophin-releasing hormone/luteinising hormone release in female rats. J Neuroendocrinol 21:299–304

    Article  CAS  PubMed  Google Scholar 

  • Weiss LM (1984) Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 8:163–169

    Article  CAS  PubMed  Google Scholar 

  • Weiss LM, Medeiros LJ, Vickery AL (1989) Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 13:202–206

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported partly by The Salt Science Research Foundation, No. 0910, and by Grant-in-aids for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.

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Correspondence to Kazuhiro Takahashi.

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Takahashi, K., Shoji, I., Shibasaki, A. et al. Presence of Kisspeptin-like Immunoreactivity in Human Adrenal Glands and Adrenal Tumors. J Mol Neurosci 41, 138–144 (2010). https://doi.org/10.1007/s12031-009-9306-4

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  • DOI: https://doi.org/10.1007/s12031-009-9306-4

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