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Departments of Cell Biology, Physiology, and Immunology (F.G., M.L.B., L.P., E.A., M.T.-S.), and Pathology (C.M.), University of Cordoba, 14004 Cordoba, Spain; Departments of Physiology (J.E.C., C.D.) and Medicine (F.F.C.), University of Santiago de Compostela, 15705 Santiago de Compostela, Spain; Center for Molecular Biotechnology, Queensland University of Technology (L.K.C., A.C.H.), Brisbane, Queensland, Australia; Department of Cell Biology and Genetics, University of Alcala (R.P.), 28871 Madrid, Spain; and Department of Morphology, University Autonoma (M.N.), 28029 Madrid, Spain
Address all correspondence and requests for reprints to: Dr. Manuel Tena-Sempere, Physiology Section, Department of Cell Biology, Physiology, and Immunology, Faculty of Medicine, University of Cordoba, Avda. Menéndez Pidal s/n, 14004 Cordoba, Spain. E-mail: fi1tesem{at}uco.es.
Ghrelin, the endogenous ligand for the GH secretagogue receptor (GHS-R), has been primarily linked to the central neuroendocrine regulation of GH secretion and food intake, although additional peripheral actions of ghrelin have also been reported. In this context, the expression of ghrelin and its cognate receptor has been recently demonstrated in rat testis, suggesting a role for this molecule in the direct control of male gonadal function. However, whether this signaling system is present in human testis remains largely unexplored. In this study we report the expression and cellular location of ghrelin and its functional receptor, the type 1a GHS-R, in adult human testis. In addition, evaluation of ghrelin and GHS-R1a immunoreactivity in testicular tumors and dysgenetic tissue is presented. The expression of the mRNAs encoding ghrelin and GHS-R1a was demonstrated in human testis specimens by RT-PCR, followed by direct sequencing. In normal testis, ghrelin immunostaining was demonstrated in interstitial Leydig cells and, at lower intensity, in Sertoli cells within the seminiferous tubules. In contrast, ghrelin was not detected in germ cells at any stage of spermatogenesis. The cognate ghrelin receptor showed a wider pattern of cellular distribution, with detectable GHS-R1a protein in germ cells, mainly in pachytene spermatocytes, as well as in somatic Sertoli and Leydig cells. Ghrelin immunoreactivity was absent in poorly differentiated Leydig cell tumor, which retained the expression of GHS-R1a peptide. In contrast, highly differentiated Leydig cell tumors expressed both the ligand and the receptor. The expression of ghrelin and GHS-R1a was also detected in dysgenetic Sertoli cell-only seminiferous tubules, whereas germ cell tumors (seminoma and embryonal carcinoma) were negative for ghrelin and were weakly positive for GHS-R1a. In conclusion, our results demonstrate that ghrelin and the type 1a GHS-R are expressed in adult human testis and testicular tumors. Overall, the expression of ghrelin and its functional receptor in human and rat testis, with roughly similar patterns of cellular distribution, is highly suggestive of a conserved role for this newly discovered molecule in the regulation of mammalian testicular function.
This work was supported by Grants BFI2000-0419-CO3-03 and BFI2002-00176 from DGESIC (Ministerio de Ciencia y Tecnología, Spain), European Union Research Contract EDEN QLK4-CT-2002-00603, and the National Health and Medical Research Council of Australia.
Abbreviations: AMV-RT, Avian myeloblastosis virus reverse transcriptase; GHS-R, GH secretagogue receptor; HPRT, hypoxanthine guanine phosphoribosyl transferase; SCF, stem cell factor; SCO, Sertoli cell-only syndrome.
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