Gülfidan COŞKUN, Hülya ÖZGÜR, Sait POLAT

Pankreas-Kemik-Testis Ekseni

Kemik; hareket ve destek fonksiyonuna sahip vücudun en büyük organıdır. Hormonal uyarılarla regüle olan kemik dokunun, kendisi de endokrin bir organ olarak davranır. Osteokalsin başta olmak üzere pek çok peptid yapıda hormon salgılar. Osteoblastlarda sentezlenen osteokalsin’in: “karboksile (inaktif) osteokalsin ve dekarboksile (aktif) osteokalsin” olmak üzere 2 formu bulunmaktadır. İnaktif osteokalsin, kemik matriksinde bulunurken aktif osteokalsin kan dolaşımına verilir ve multifonksiyonel hormon olarak davranır. Aktif osteokalsin; enerji metabolizması ve erkek fertilitesini regüle eder. Geçtiğimiz on yılda sayısız epidemiyolojik, genetik ve biyokimyasal çalışmada, kemik dokunun aktif osteokalsin aracılığıyla pankreas, adipoz doku ve gonadlar ile arasındaki hormonal bağlantıları gösterilmiştir. Bu makalede hipotalamohipofizyal testis ekseninden bağımsız olarak testosteron sentezini uyaran yeni tanımlanmış pankreas-kemik-testis ekseninin mekanizması tartışılmıştır.

Anahtar Kelimeler:

Pankreas, kemik, testis, insülin, osteokalsin, testosteron

Pancreas-Bone-Testis Axis

Bone which has movement and support functions, is the largest organ of the body. Bone is regulated by hormonal signal but it also acts as an endocrine organ. Many peptide hormones such asosteocalcin are secreted from bone. Osteocalcin which is an osteoblast derived hormone, has two forms: “carboxylated (inactive) osteocalcin and decarboxylated (active) osteocalcin”. While inactive osteocalcin is found in bone matrix, active osteocalcin is given to blood circulation and acts as a multifunctional hormone. In the past ten years, numerous epidemiological, genetic and biochemical studies have revealed hormonal links between bone and pancreas, adipose tissue, gonads via active osteocalcin. In this review, a newly defined pathwaycalled pancreas-bone-testis axis which stimulates testosterone synthesis independent of hypothalamic hypophyseal testicular axis, is discussed.

Keywords:

Pancreas, bone, testis, ınsulin, osteocalcin, testosterone,

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Cannon WB. Organization for physiological homeostasis. Physiol. Rev. 1929;9:399-431.
Guntur AR, Rosen CJ. Bone as an endocrine organ. Endocr Pract. 2012;18:758-62.
Karsenty G, Oury F. Biology without walls: The novel endocrinology of bone. Annu Rev Physiol. 2012;74:87-105.
Karsenty G, Ferron M. The contribution of bone to whole-organism physiology. Nature. 2012;18:314-20.
Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith CE et al. Endocrine regulation of male fertility by the skeleton. Cell. 2011;144:796-809.
Karsenty G. The mutual dependence between bone and gonads. J Endocrinol. 2012;213:107-14. 7. Ferron M, Lacombe J. Regulation of energy metabolism by the skeleton: osteocalcin and beyond. Arch Biochem Biophys. 2014;561:137-46.
Oury F, Ferron M, Huizhen W, Confavreux C, Xu L, Lacombe J et al. Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis. J Clin Invest. 2013;123:2421-33.
Kini U, Nandeesh BN. Physiology of bone formation, remodeling, and metabolism. In Radionuclide and Hybrid Bone Imaging (Ed I Fogelman). Berlin, Springer Verlag, 2012.
Quarles LD. Endocrine functions of bone in mineral metabolism regulation. J Clin Invest. 2008;118:3820-8.
Patti A, Gennari L, Merlotti D, Dotta F, Nuti R. Endocrine actions of osteocalcin. Int J Endocrinol. 2013;2013:846480.
Kim Y, Paik Y, Rhiey YJ, Suh SH. Integrative physiology: Defined novel metabolic roles of osteocalcin. Korean Med Sci. 2010;25:985-91.
Schwetz V, Pieber T, Obermayer-Pietsch B. The endocrine role of the skeleton: background and
clinical evidence. Eur J Endocrinol. 2012;166:959-67.
Rached MT, Kode A, Silva BC, Jung DY, Gray S, Ong H et al. FOXO1 expression in osteoblasts regulates glucose homeostasis through regulation of osteocalcin in mice. J Clin Invest. 2010;120:357-68.
Novack DV. The FOX(O1)blasts off. Cell Metab. 2010;11:175-6.
Wei J, Ferron M, Clarke CJ, Hannun YA, Jiang H, Blaner WS et al. Bone-specific insulin resistance
disrupts whole-body glucose homeostasis via decreased osteocalcin activation. J Clin Invest. 2014;124:1-13.
Clemens TL, Karsenty G. The osteoblast: an insulin target cell controlling glucose homeostasis. J Bone Miner Res. 2011;26:677-80.
Fulzele K, Riddle RC, DiGirolamo DJ, Cao X, Wan C, Chen D et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. 2010;142:309-19.
Ducy P. The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism. Diabetologia. 2011;54:1291-7.
Foresta C, Strapazzon G, De Toni L, Gianesello L, Calcagno A, Pilon C et al. Evidence for osteocalcin production by adipose tissue and its role in human metabolism. J Clin Endocrinol Metab. 2010;95:3502-6.
Hinoi E, Gao N, Jung DY, Yadav V, Yoshizawa T, Myers MG Jr et al. The sympathetic tone mediates leptin’s inhibition of insulin secretion by modulating osteocalcin bioactivity. J Cell Biol. 2008;183:1235-42.
Turner RT, Kalra SP, Wong CP, Philbrick KA, Lindenmaier LB, Boghossian S et al. Peripheral leptin regulates bone formation. J Bone Miner Res. 2013;28:22-34.
Karsenty G. Convergence between bone and energy homeostases: leptin regulation of bone mass. Cell Metab. 2006;4:341-8.
Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 2009;138:976-89.
Ducy P, Karsenty G. The two faces of serotonin in bone biology. J Cell Biol. 2010;191:7-13.
Kıeffer TJ, Habener JF. The adipoinsular axis: effects of leptin on pancreatic b-cells. Am J Physiol Endocrinol Metab. 2000;278:E1-E14.
Haider SG. Cell biology of leydig cells in the testis. Int Rev Cytol. 2004;233:181-241.
Kohn FM. Testosterone and body functions. Aging Male. 2006;9:183-8
Vanderschueren D, Vandenput L, Boonen S, Lindberg MK, Bouillon R, Ohlsson C. Androgens and bone. Endocr Rev. 2005;25:389-425.
Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev. 2005;26:833-76.
Riggs BL, Khosla S, Melton LJ. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002;23:279-302.
Pi M, Quarles LD. Multiligand specificity and wide tissue expression of GPRC6A reveals new endocrine networks. Endocrinology. 2012;153:2062-9.
Pi M, Chen L, Huang MZ, Zhu W, Ringhofer B, Luo J et al. GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome. PLoS One. 2008;3:e3858.
Karsenty G, Oury F. Regulation of male fertility by the bone-derived hormone hormone osteocalcin. Mol Cell Endocrinol. 2014;382:521-6.
Kanazawa I, Tanaka K, Ogawa N, Yamauchi M, Yamaguchi T, Sugimoto T. Undercarboxylated osteocalcin is positively associated with free testosterone in male patients with type 2 diabetes mellitus. Osteoporos Int. 2013;24:1115-9.
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