Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers

Journal of Clinical Endocrinology and Metabolism

Volumn 98, Issue 11, 2013, Pages 4464-4474

  Jayasena, C N ^a   Comninos, A N ^a   Nijher, G M K ^a   Abbara, A ^a   De Silva, A ^a   Veldhuis, J D ^b   Ratnasabapathy, R ^a   Izzi Engbeaya, C ^a   Lim, A ^c   Patel, D A ^c   Ghatei, M A ^a   Bloom, S R ^a   Dhillo, Waljit S ^a  

^a HAMMERSMITH HOSPITAL   (United Kingdom)

^b MAYO CLINIC   (United States)

^c CHARING CROSS HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

GONADORELIN; LUTEINIZING HORMONE; METASTIN; PLACEBO; PROGESTERONE;

ADULT; ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; FEMALE; HUMAN; HUMAN EXPERIMENT; LONG TERM EXPOSURE; LUTEAL PHASE; LUTEINIZING HORMONE BLOOD LEVEL; MENSTRUAL CYCLE; NORMAL HUMAN; PRIORITY JOURNAL; PROGESTERONE BLOOD LEVEL; SINGLE BLIND PROCEDURE;

ADULT; ANOVULATION; CROSS-OVER STUDIES; ENDOMETRIUM; FEMALE; FOLLICULAR PHASE; HEALTHY VOLUNTEERS; HORMONES; HUMANS; INJECTIONS, SUBCUTANEOUS; KISSPEPTINS; LUTEAL PHASE; MENSTRUAL CYCLE; OVULATION; PLACEBOS; PROSPECTIVE STUDIES; SINGLE-BLIND METHOD; YOUNG ADULT;

EID: 84887417775     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/jc.2013-1069     Document Type: Article

References (47)

1. Clements MK, McDonald TP, Wang R, et al. FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled receptor GPR54. Biochem Biophys ResCommun. 2001;285: 1189-1193.
2. Kotani M, Detheux M, Vandenbogaerde A, et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001; 276: 34631-34636.
3. Ohtaki T, Shintani Y, Honda S, et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001;411: 613-617.
4. Muir AI, Chamberlain L, Elshourbagy NA, et al. AXOR12, a novel humanGprotein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem. 2001;276: 28969-28975.
5. Clarkson J, Herbison AE. Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. Endocrinology. 2006; 147: 5817-5825.
6. Rometo AM, Krajewski SJ, Voytko ML, Rance NE. Hypertrophy and increased kisspeptin gene expression in the hypothalamic infundibular nucleus of postmenopausal women and ovariectomized monkeys. J Clin Endocrinol Metab. 2007;92: 2744-2750.
7. Richard N, Galmiche G, Corvaisier S, Caraty A, Kottler ML. KiSS-1 and GPR54 genes are co-expressed in rat gonadotrophs and differentially regulated in vivo by oestradiol and gonadotrophin-releasing hormone. J Neuroendocrinol. 2008;20: 381-393.
8. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A. 2003;100: 10972-10976.
9. Seminara SB, Messager S, Chatzidaki EE, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003;349: 1614-1627.
10. Topaloglu AK, Tello JA, Kotan LD, et al. Inactivating KISS1 mutation and hypogonadotropic hypogonadism. N Engl J Med. 2012; 366: 629-635.
11. Thompson EL, Patterson M, Murphy KG, et al. Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic- pituitary-gonadal axis. J Neuroendocrinol. 2004;16: 850-858.
12. Patterson M, Murphy KG, Thompson EL, Patel S, Ghatei MA, Bloom SR. Administration of kisspeptin-54 into discrete regions of the hypothalamus potently increases plasma luteinising hormone and testosterone in male adult rats. J Neuroendocrinol. 2006;18: 349-354.
13. Tovar S, Vázquez MJ, Navarro VM, et al. Effects of single or repeated intravenous administration of kisspeptin upon dynamic LH secretion in conscious male rats. Endocrinology. 2006;147:2696- 2704.
14. Gottsch ML, Cunningham MJ, Smith JT, et al.Arole for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology. 2004;145: 4073-4077.
15. Messager S, Chatzidaki EE, Ma D, et al. Kisspeptin directly stimulates gonadotropin-releasing hormone release viaGprotein-coupled receptor 54. Proc Natl Acad Sci U S A. 2005;102: 1761-1766.
16. Seminara SB, Dipietro MJ, Ramaswamy S, Crowley WF Jr, Plant TM. 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. 2006;147: 2122-2126.
17. Caraty A, Smith JT, Lomet D, et al. Kisspeptin synchronizes preovulatory surges in cyclical ewes and causes ovulation in seasonally acyclic ewes. Endocrinology. 2007;148: 5258-5267.
18. Redmond JS, Macedo GG, Velez IC, Caraty A, Williams GL, Amstalden M. Kisspeptin activates the hypothalamic-adenohypophyseal- gonadal axis in prepubertal ewe lambs. Reproduction. 2011; 141: 541-548.
19. Dhillo WS, Chaudhri OB, Patterson M, et al. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis inhumanmales. J Clin Endocrinol Metab. 2005;90: 6609-6615.
20. Chan YM, Butler JP, Pinnell NE, et al. Kisspeptin resets the hypothalamic GnRH clock in men. J Clin Endocrinol Metab. 2011;96: E908-E915.
21. George JT, Veldhuis JD, Roseweir AK, et al. Kisspeptin-10 is a potent stimulator ofLHand increases pulse frequency in men. J Clin Endocrinol Metab. 2011;96:E1228-E1236.
22. Jayasena CN, Nijher GM, Comninos AN, et al. The effects of kisspeptin- 10 on reproductive hormone release show sexual dimorphism in humans. J Clin Endocrinol Metab. 2011;96:E1963- E1972.
23. Dhillo WS, Chaudhri OB, Thompson EL, et al. Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women. J Clin Endocrinol Metab. 2007;92: 3958-3966.
24. Chan YM, Butler JP, Sidhoum VF, Pinnell NE, Seminara SB. Kisspeptin administration to women: a window into endogenous kissdoi peptin secretion and GnRH responsiveness across the menstrual cycle. J Clin Endocrinol Metab. 2012;97:E1458-E1467.
25. Jayasena CN, Nijher GM, Chaudhri OB, et al. Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis. J Clin Endocrinol Metab. 2009;94:4315- 4323.
26. Jayasena CN, Nijher GM, Abbara A, et al. Twice-weekly administration of kisspeptin-54 for 8 weeks stimulates release of reproductive hormones inwomenwith hypothalamic amenorrhea. Clin Pharmacol Ther. 2010;88: 840-847.
27. Liu PY, Keenan DM, Kok P, Padmanabhan V, O'Byrne KT, Veldhuis JD. Sensitivity and specificity of pulse detection using a new deconvolution method.AmJ Physiol Endocrinol Metab. 2009;297: E538-E544.
28. Knobil E, Plant TM, Wildt L, Belchetz PE, Marshall G. Control of the rhesus monkey menstrual cycle: permissive role of hypothalamic gonadotrophin-releasing hormone. Science. 1980;207: 1371-1373.
29. Grimes EM, Taymor ML, Thompson IE. Induction of timed ovulation with synthetic luteinizing hormone-releasing hormone in women undergoing insemination therapy. I. Effect of a single parenteral administration at midcycle. Fertil Steril. 1975;26: 277-282.
30. Clarkson J, d'Anglemont de Tassigny X, et al. Kisspeptin-GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge. J Neurosci. 2008;28: 8691-8697.
31. Smith JT, Popa SM, Clifton DK, Hoffman GE, Steiner RA. Kiss1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge. J Neurosci. 2006;26: 6687-6694.
32. Adachi S, Yamada S, Takatsu Y, et al. Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats. J Reprod Dev. 2007;53: 367-378.
33. Inoue N, Sasagawa K, Ikai K, et al. Kisspeptin neurons mediate reflex ovulation in the musk shrew (Suncus murinus). Proc Natl Acad Sci U S A. 2011;108: 17527-17532.
34. Matsui H, Takatsu Y, Kumano S, Matsumoto H, Ohtaki T. Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat. Biochem Biophys Res Commun. 2004;320: 383-388.
35. Hall JE, Taylor AE, Martin KA, Rivier J, Schoenfeld DA, Crowley WFJr. Decreased release of gonadotropin-releasing hormone during the preovulatory midcycle luteinizing hormone surge in normal women. Proc Natl Acad Sci U S A. 1994;91: 6894-6898.
36. Adams JM, Taylor AE, Schoenfeld DA, CrowleyWFJr, Hall JE. The midcycle gonadotropin surge in normal women occurs in the face of an unchanging gonadotropin-releasing hormone pulse frequency. J Clin Endocrinol Metab. 1994;79: 858-864.
37. Sonigo C, Bouilly J, Carré N, et al. Hyperprolactinemia-induced ovarian acyclity is reversed by kisspeptin administration. J Clin Invest. 2012;122: 3791-3795.
38. Kousta E, White DM, Franks S. Modern use of clomiphene citrate in induction of ovulation. Hum Reprod Update. 1997;3: 359-365.
39. Hart R, Norman R. Polycystic ovarian syndrome-prognosis and outcomes. Best Pract Res Clin Obstet Gynaecol. 2006;20: 751-778.
40. Min JK, Breheny SA, MacLachlan V, Healy DL. What is the most relevant standard of success in assisted reproduction? The singleton, term gestation, live birth rate per cycle initiated: the BESST endpoint for assisted reproduction. Hum Reprod. 2004;19: 3-7.
41. Matsui H 2012 Testosterone depletion by continuous administration of kisspeptin analogues. Paper presented at: Second World Conference of Kisspeptin Signaling in the Brain; November 9, 2012; Tokyo, Japan.
42. d'Anglemont de Tassigny X, Fagg LA, Carlton MB, Colledge WH. Kisspeptin can stimulate gonadotropin-releasing hormone (GnRH) release by a direct action at GnRH nerve terminals. Endocrinology. 2008;149: 3926-3932.
43. d'Anglemont de Tassigny X, Ackroyd KJ, Chatzidaki EE, Colledge WH. Kisspeptin signaling is required for peripheral but not central stimulation of gonadotropin-releasing hormone neurons by NMDA. J Neurosci. 2010;30: 8581-8590.
44. Matsui H, Tanaka A, Yokoyama K, et al. Chronic administration of the metastin/kisspeptin analog KISS1-305 or the investigational agentTAK- 448suppresses hypothalamic pituitary gonadal function and depletes plasma testosterone in adult male rats. Endocrinology. 2012;153: 5297-5308.
45. Gutiérrez-Pascual E, Martínez-Fuentes AJ, Pinilla L, Tena-Sempere M, MalagónMM,Castaño JP. Direct pituitary effects of kisspeptin: activation of gonadotrophs and somatotrophs and stimulation of luteinising hormone and growth hormone secretion. J Neuroendocrinol. 2007;19: 521-530.
46. Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM. Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci U S A. 2005;102: 2129-2134.
47. Young J, George JT, Tello JA, et al. Kisspeptin restores pulsatile LH secretion in patients with neurokinin B signaling deficiencies: physiological, pathophysiological and therapeutic implications. Neuroendocrinology. 2013;97: 193-202.