Kisspeptin-54 at high doses acutely induces testicular degeneration in adult male rats via central mechanisms

British Journal of Pharmacology

Volumn 156, Issue 4, 2009, Pages 609-625

  Thompson, E L ^a   Amber, V ^a   Stamp, G W H ^a   Patterson, M ^a   Curtis, A E ^a   Cooke, J H ^a   Appleby, G F ^a   Dhillo, W S ^a   Ghatei, M A ^a   Bloom, S R ^a   Murphy, K G ^a  

^a HAMMERSMITH HOSPITAL   (United Kingdom)

Author keywords

GPR54; Metastin; Seminiferous tubules; Testis

Indexed keywords

CETRORELIX; FOLLITROPIN; GONADORELIN; INHIBIN B; LUTEINIZING HORMONE; METASTIN; TESTOSTERONE; G PROTEIN COUPLED RECEPTOR; INHIBIN; KISS1R PROTEIN, RAT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANNULATION; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFECT; DRUG MECHANISM; HISTOPATHOLOGY; HYPOTHALAMUS HYPOPHYSIS GONAD SYSTEM; MALE; NONHUMAN; PRIORITY JOURNAL; RAT; TESTICULAR DEGENERATION; TESTIS; TESTIS DISEASE; TESTIS WEIGHT; TISSUE DEGENERATION; ANIMAL; BLOOD; HYPOPHYSIS ADRENAL SYSTEM; HYPOTHALAMUS HYPOPHYSIS SYSTEM; INTRACEREBROVENTRICULAR DRUG ADMINISTRATION; PATHOLOGY; PHYSIOLOGY; SUBCUTANEOUS DRUG ADMINISTRATION; TIME; WISTAR RAT;

ANIMALS; DOSE-RESPONSE RELATIONSHIP, DRUG; HYPOTHALAMO-HYPOPHYSEAL SYSTEM; INHIBINS; INJECTIONS, INTRAVENTRICULAR; INJECTIONS, SUBCUTANEOUS; MALE; PITUITARY-ADRENAL SYSTEM; RATS; RATS, WISTAR; RECEPTORS, G-PROTEIN-COUPLED; TESTIS; TIME FACTORS;

EID: 65349115351     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2008.00061.x     Document Type: Article

References (60)

1. Alexander SPH, Mathie A, Peters JA (2006). Guide to Receptors and Channels (GRAC), 2nd edn. Br J Pharmacol 147 (Suppl. 3 S1 S180.
2. d'Anglemont de Tassigny X, Fagg LA, Dixon JP, Day K, Leitch HG, Hendrick AG et al. (2007). Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene. Proc Natl Acad Sci USA 104 : 10714 10719.
3. Beak SA, Heath MM, Small CJ, Morgan DG, Ghatei MA, Taylor AD et al. (1998). Glucagon-like peptide-1 stimulates luteinizing hormone-releasing hormone secretion in a rodent hypothalamic neuronal cell line. J Clin Invest 101 : 1334 1341.
4. Bergh A, Soder O (2007). Studies of cryptorchidism in experimental animal models. Acta Paediatr 96 : 617 621.
5. Bergh A, Collin O, Lissbrant E (2001). Effects of acute graded reductions in testicular blood flow on testicular morphology in the adult rat. Biol Reprod 64 : 13 20.
6. 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.
7. Chatani F (2006). Possible mechanism for testicular focal necrosis induced by hCG in rats. J Toxicol Sci 31 : 291 303.
8. 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.
9. Dhillo WS, Chaudhri OB, Thompson EL, Murphy KG, Patterson M, Ramachandran R et al. (2007). Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women. J Clin Endocrinol Metab 92 : 3958 3966.
10. Drury RAB, Wallington EA (1967). Carleton's Histological Techniques. Oxford University Press : London.
11. Funes S, Hedrick JA, Vassileva G, Markowitz L, Abbondanzo S, Golovko A et al. (2003). The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem Biophys Res Commun 312 : 1357 1363.
12. 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.
13. Habenicht UF, el Etreby MF, Neumann F (1985). Possible vascular effects of an LH-RH agonist on the peripheral circulation of the rat testes. Andrologia 17 : 440 443.
14. Harris GC, Levine JE (2003). Pubertal acceleration of pulsatile gonadotropin-releasing hormone release in male rats as revealed by microdialysis. Endocrinology 144 : 163 171.
15. Heiskanen P, Billig H, Toppari J, Kaleva M, Arsalo A, Rapola J et al. (1996). Apoptotic cell death in the normal and cryptorchid human testis: the effect of human chorionic gonadotropin on testicular cell survival. Pediatr Res 40 : 351 356.
16. Hjertkvist M, Lackgren G, Ploen L, Bergh A (1993). Does HCG treatment induce inflammation-like changes in undescended testes in boys? J Pediatr Surg 28 : 254 258.
17. Irwig MS, Fraley GS, Smith JT, Acohido BV, Popa SM, Cunningham MJ et al. (2004). Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat. Neuroendocrinology 80 : 264 272.
18. Karaman IM, Kaya C, Ozturk M, Pirincci N, Yimazgumrukcu G, Tuken M (2006). The effects of human chorionic gonadotrophin on normal testicular tissue of rats: dose-dependence and reversibility. BJU Int 97 : 1116 1118.
19. Kerr JB, Sharpe RM (1986). Effects and interactions of LH and LHRH agonist on testicular morphology and function in hypophysectomized rats. J Reprod Fertil 76 : 175 192.
20. Kerr JB, Sharpe RM (1989). Focal disruption of spermatogenesis in the testis of adult rats after a single administration of human chorionic gonadotrophin. Cell Tissue Res 257 : 163 169.
21. Kinoshita M, Tsukamura H, Adachi S, Matsui H, Uenoyama Y, Iwata K et al. (2005). Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats. Endocrinology 146 : 4431 4436.
22. Koduri S, Hild SA, Pessaint L, Reel JR, Attardi BJ (2008). Mechanism of action of l-CDB-4022, a potential nonhormonal male contraceptive, in the seminiferous epithelium of the rat testis. Endocrinology 149 : 1850 1860.
23. Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E 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.
24. van Kroonenburgh MJ, Beck JL, Vemer HM, Rolland R, Thomas CM, Herman CJ (1986). Effects of a single injection of a new depot formulation of an LH-releasing hormone agonist on spermatogenesis in adult rats. J Endocrinol 111 : 449 454.
25. Lala R, Matarazzo P, Chiabotto P, Gennari F, Cortese MG, Canavese F et al. (1997). Early hormonal and surgical treatment of cryptorchidism. J Urol 157 : 1898 1901.
26. Lapatto R, Pallais JC, Zhang D, Chan YM, Mahan A, Cerrato F et al. (2007). Kiss1-/- mice exhibit more variable hypogonadism than Gpr54-/- mice. Endocrinology 148 : 4927 4936.
27. Lee DK, Nguyen T, O'Neill GP, Cheng R, Liu Y, Howard AD et al. (1999). Discovery of a receptor related to the galanin receptors. FEBS Lett 446 : 103 107.
28. Lefebvre FA, Belanger A, Pelletier G, Labrie F (1984). Recovery of gonadal functions in the adult male rat following cessation of five-month daily treatment with an LHRH agonist. J Androl 5 : 181 192.
29. Leon MD, Chiauzzi VA, Calvo JC, Charreau EH, Chemes HE (1987). Acute hCG administration induces seminiferous tubule damage in the adult rat. Acta Physiol Pharmacol Latinoam 37 : 277 288.
30. Markey CM, Jequier AM, Meyer GT, Martin GB (1994). Testicular morphology and androgen profiles following testicular ischaemia in rams. J Reprod Fertil 101 : 643 650.
31. Matsui H, Takatsu Y, Kumano S, Matsumoto H, Ohtaki T (2004). Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat. Biochem Biophys Res Commun 320 : 383 388.
32. Mead EJ, Maguire JJ, Kuc RE, Davenport AP (2007a). Kisspeptins: a multifunctional peptide system with a role in reproduction, cancer and the cardiovascular system. Br J Pharmacol 151 : 1143 1153.
33. Mead EJ, Maguire JJ, Kuc RE, Davenport AP (2007b). 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.
34. Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D, Dixon J et al. (2005). Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci USA 102 : 1761 1766.
35. 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.
36. Navarro VM, Castellano JM, Fernandez-Fernandez R, Tovar S, Roa J, Mayen A et al. (2005a). Effects of KiSS-1 peptide, the natural ligand of GPR54, on follicle-stimulating hormone secretion in the rat. Endocrinology 146 : 1689 1697.
37. Navarro VM, Castellano JM, Fernandez-Fernandez R, Tovar S, Roa J, Mayen A et al. (2005b). Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54. Endocrinology 146 : 156 163.
38. 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.
39. Patterson M, Murphy KG, Thompson EL, Patel S, Ghatei MA, Bloom SR (2006). Administration of kisspeptin-54 into discrete regions of the hypothalamus potently increases plasma luteinising hormone and testosterone in male adult rats. J Neuroendocrinol 18 : 349 354.
40. Pierik FH, Burdorf A, de Jong FH, Weber RF (2003). Inhibin B: a novel marker of spermatogenesis. Ann Med 35 : 12 20.
41. Rajfer J, Swerdloff RS, Heber DM (1984). Testicular histology following chronic gonadotropin-releasing hormone agonist treatment. Fertil Steril 42 : 765 771.
42. Ramaswamy S, Marshall GR, McNeilly AS, Plant TM (1999). Evidence that in a physiological setting Sertol cell number is the major determinant of circulating concentrations of inhibin B in the adult male rhesus monkey (Macaca mulatta). J Androl 20 : 430 434.
43. Ramaswamy S, Seminara SB, Pohl CR, Dipietro MJ, Crowley WF, Jr., Plant TM et al. (2007). Effect of continuous intravenous administration of human metastin 45-54 on the neuroendocrine activity of the hypothalamic-pituitary- testicular axis in the adult male rhesus monkey (Macaca mulatta). Endocrinology 148 : 3364 3370.
44. Rivier C, Rivier J, Vale W (1979). Chronic effects of [D-Trp6,Pro9-NEt]luteinizing hormone-releasing factor on reproductive processes in the male rat. Endocrinology 105 : 1191 1201.
45. Rossi M, Choi SJ, O'Shea D, Miyoshi T, Ghatei MA, Bloom SR (1997). Melanin-concentrating hormone acutely stimulates feeding, but chronic administration has no effect on body weight. Endocrinology 138 : 351 355.
46. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E (2003). Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA 100 : 10972 10976.
47. Russell LD, Ettlin RA, Hikim AP, Clegg ED (1990). Histopathology of the testis- quantitative evaluation of testis histopathology. In : Russel LD, Ettlin RA, Sinha Hikim AP, Clegg ED (ed.). Histological and Histopathological Evaluation of the Testis. Cache River Press : St Louis, pp. 240 264.
48. Sandow J, Von RW, Jerzabek G, Stoll W (1978). Pituitary gonadotropin inhibition by a highly active analog of luteinizing hormone-releasing hormone. Fertil Steril 30 : 205 209.
49. 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.
50. Seminara SB, Dipietro MJ, Ramaswamy S, Crowley WF, Jr., Plant TM (2006). Continuous human metastin 45-54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-releasing hormone release monitored indirectly in the juvenile male Rhesus monkey (Macaca mulatta): a finding with therapeutic implications. Endocrinology 147 : 2122 2126.
51. Semple RK, Achermann JC, Ellery J, Farooqi IS, Karet FE, Stanhope RG et al. (2005). Two novel missense mutations in g protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism. J Clin Endocrinol Metab 90 : 1849 1855.
52. Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM (2005). Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci USA 102 : 2129 2134.
53. Sharpe RM, Turner KJ, McKinnell C, Groome NP, Atanassova N, Millar MR et al. (1999). Inhibin B levels in plasma of the male rat from birth to adulthood: effect of experimental manipulation of Sertoli cell number. J Androl 20 : 94 101.
54. Smith JT, Pereira A, Rao A, Morgan K, Millar R, Clarke IJ (2007). Evidence that Pituitary Gonadotropes are not a Major Target of Kisspeptin. The Endocrine Society's 89th Annual Meeting. 2-6-2007. Ref Type: Abstract.
55. Tena-Sempere M (2006). GPR54 and kisspeptin in reproduction. Hum Reprod Update 12 : 631 639.
56. Terao Y, Kumano S, Takatsu Y, Hattori M, Nishimura A, Ohtaki T et al. (2004). Expression of KiSS-1, a metastasis suppressor gene, in trophoblast giant cells of the rat placenta. Biochim Biophys Acta 1678 : 102 110.
57. Thompson EL, Patterson M, Murphy KG, Smith KL, Dhillo WS, Todd JF et al. (2004). Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. J Neuroendocrinol 16 : 850 858.
58. Thompson EL, Murphy KG, Patterson M, Bewick GA, Stamp GW, Curtis AE et al. (2006). Chronic subcutaneous administration of kisspeptin-54 causes testicular degeneration in adult male rats. Am J Physiol Endocrinol Metab 291 : E1074 E1082.
59. Ward JA, Furr BJ, Valcaccia B, Curry B, Bardin CW, Gunsalus GL et al. (1989). Prolonged suppression of rat testis function by a depot formulation of Zoladex, a GnRH agonist. J Androl 10 : 478 486.
60. Zheng JY, Fulu MY (2006). Decrease of genital organ weights and plasma testosterone levels in rats following oral administration of leuprolide microemulsion. Int J Pharm 307 : 209 215.