176 A Caraty and I Francesch<strong>in</strong>iFig. 5. LH secretion and ensu<strong>in</strong>govulation <strong>in</strong> ewes treated dur<strong>in</strong>gthe non-breed<strong>in</strong>g season with an<strong>in</strong>travenous <strong>in</strong>fusion of kisspept<strong>in</strong>(20 lg ⁄ h for 48 h). The upperpanels show two examples of plasmaLH levels <strong>in</strong> kisspept<strong>in</strong>-<strong>in</strong>fusedewes, <strong>in</strong>dicat<strong>in</strong>g that the treatmentled to <strong>in</strong>creased secretion but thepreovulatory surge did not occuruntil 25 h later. This strongly suggeststhat the <strong>in</strong>fusion <strong>in</strong>itiated anartificial follicular phase and thatthe <strong>in</strong>creased oestrogen result<strong>in</strong>gfrom this activated a positivefeedback response. The experimentwas repeated <strong>in</strong> France and <strong>in</strong>Australia with similar results.Approximately 80% of the ewestreated with kisspept<strong>in</strong> ovulated, asevidenced by result<strong>in</strong>g corporalutea on the ovaries. Adapted fromCaraty et al. (2007)of us<strong>in</strong>g kisspept<strong>in</strong> for the control of the gonadotrop<strong>in</strong>axis provides hope for resolv<strong>in</strong>g all fertility problems.Who knows if this is the end of the story, or perhaps anew molecule activat<strong>in</strong>g kisspept<strong>in</strong> might be discovered<strong>in</strong> another 30 years’ time!ReferencesBlache D, Fabre-Nys CJ, Venier G, 1991: Ventromedialhypothalamus as a target for oestradiol action on proceptivity,receptivity and lute<strong>in</strong>iz<strong>in</strong>g hormone surge of the ewe.Bra<strong>in</strong> Res 546, 241–249.Caraty A, Fabre-Nys C, Delaleu B, Locatelli A, Bruneau G,Karsch FJ, Herbison A, 1998: Evidence that the mediobasalhypothalamus is the primary site of action of estradiol <strong>in</strong><strong>in</strong>duc<strong>in</strong>g the preovulatory gonadotrop<strong>in</strong> releas<strong>in</strong>g hormonesurge <strong>in</strong> the ewe. Endocr<strong>in</strong>ology 139, 1752–1760.Caraty A, Smith JT, Lomet D, Ben Said S, Morrissey A,Cognie J, Doughton B, Baril G, Briant C, Clarke IJ, 2007:Kisspept<strong>in</strong> synchronizes preovulatory surges <strong>in</strong> cyclical ewesand causes ovulation <strong>in</strong> seasonally acyclic ewes. Endocr<strong>in</strong>ology148, 5258–5267.Clarke IJ, Cumm<strong>in</strong>s JT, Jenk<strong>in</strong> M, Phillips DJ, 1989: Theoestrogen-<strong>in</strong>duced surge of LH requires a ‘signal’ pattern ofgonadotroph<strong>in</strong>-releas<strong>in</strong>g hormone <strong>in</strong>put to the pituitarygland <strong>in</strong> the ewe. J Endocr<strong>in</strong>ol 122, 127–134.Clarkson J, Herbison AE, 2006: Postnatal development ofkisspept<strong>in</strong> neurons <strong>in</strong> mouse hypothalamus; sexual dimorphismand projections to gonadotrop<strong>in</strong>-releas<strong>in</strong>g hormoneneurons. Endocr<strong>in</strong>ology 147, 5817–5825.Dhillo WS, Chaudhri OB, Patterson M, Thompson EL,Murphy KG, Badman MK, McGowan BM, Amber V,Patel S, Ghatei MA, Bloom SR, 2005: Kisspept<strong>in</strong>-54stimulates the hypothalamic-pituitary gonadal axis <strong>in</strong>human males. J Cl<strong>in</strong> Endocr<strong>in</strong>ol Metab 90, 6609–6615.Dhillo WS, Chaudhri OB, Thompson EL, Murphy KG,Patterson M, Ramachandran R, Nijher GK, Amber V,Kokk<strong>in</strong>os A, Donaldson M, Ghatei MA, Bloom SR, 2007:Kisspept<strong>in</strong>-54 stimulates gonadotrop<strong>in</strong> release mostpotently dur<strong>in</strong>g the preovulatory phase of the menstrualcycle <strong>in</strong> women. J Cl<strong>in</strong> Endocr<strong>in</strong>ol Metab 92, 3958–3966.Dungan HM, Gottsch ML, Zeng H, Gragerov A, BergmannJE, Vassilatis DK, Clifton DK, Ste<strong>in</strong>er RA, 2007: The roleof kisspept<strong>in</strong>-GPR54 signal<strong>in</strong>g <strong>in</strong> the tonic regulation andsurge release of gonadotrop<strong>in</strong>-releas<strong>in</strong>g hormone ⁄ lute<strong>in</strong>iz<strong>in</strong>ghormone. J Neurosci 27, 12088–12095.Estrada KM, Clay CM, Pompolo S, Smith JT, Clarke IJ, 2006:Elevated Kiss-1 expression <strong>in</strong> the arcuate nucleus prior tothe cyclic preovulatory gonadotrop<strong>in</strong>-releas<strong>in</strong>g hormone ⁄lute<strong>in</strong>is<strong>in</strong>g hormone surge <strong>in</strong> the ewe suggests a stimulatoryrole for kisspept<strong>in</strong> <strong>in</strong> oestrogen-positive feedback. J Neuroendocr<strong>in</strong>ol18, 139–149.Francesch<strong>in</strong>i I, Lomet D, Cateau M, Delsol G, Tillet Y,Caraty A, 2006: Kisspept<strong>in</strong> immunoreactive cells of theov<strong>in</strong>e preoptic area and arcuate nucleus co-express estrogenreceptor alpha. Neurosci Lett 401, 225–230.Gottsch ML, Cunn<strong>in</strong>gham MJ, Smith JT, Popa SM, AcohidoBV, Crowley WF, Sem<strong>in</strong>ara S, Clifton DK, Ste<strong>in</strong>er RA,2004: A role for kisspept<strong>in</strong>s <strong>in</strong> the regulation of gonadotrop<strong>in</strong>secretion <strong>in</strong> the mouse. Endocr<strong>in</strong>ology 145, 4073–4077.Ó 2008 The Authors. Journal compilation Ó 2008 Blackwell Verlag
Control of Fertility <strong>in</strong> Females by Kisspept<strong>in</strong> 177Gottsch ML, Clifton DK, Ste<strong>in</strong>er RA, 2006: Kisspepept<strong>in</strong>-GPR54 signal<strong>in</strong>g <strong>in</strong> the neuroendocr<strong>in</strong>e reproductive axis.Mol Cell Endocr<strong>in</strong>ol 254 255, 91–96.Gu GB, Simerly RB, 1997: Projections of the sexuallydimorphic anteroventral periventricular nucleus <strong>in</strong> thefemale rat. J Comp Neurol 384, 142–164.Gutierrez-Pascual E, Mart<strong>in</strong>ez-Fuentes AJ, P<strong>in</strong>illa L, Tena-Sempere M, Malagon MM, Castano JP, 2007: Directpituitary effects of kisspept<strong>in</strong>: activation of gonadotrophsand somatotrophs and stimulation of lute<strong>in</strong>is<strong>in</strong>g hormoneand growth hormone secretion. 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Neuroendocr<strong>in</strong>ology 80, 264–272.Kadokawa H, Matsui M, Hayashi K, Matsunaga N, KawashimaC, Shimizu T, Kida K, Miyamoto A, 2008a:Peripheral adm<strong>in</strong>istration of kisspept<strong>in</strong>-10 <strong>in</strong>creases plasmaconcentrations of GH as well as LH <strong>in</strong> prepubertal Holste<strong>in</strong>heifers. J Endocr<strong>in</strong>ol 196, 331–334.Kadokawa H, Suzuki S, Hashizume T, 2008b: Kisspept<strong>in</strong>-10stimulates the secretion of growth hormone and prolact<strong>in</strong>directly from cultured bov<strong>in</strong>e anterior pituitary cells. AnimReprod Sci 105, 404–408.Kauffman AS, Gottsch ML, Roa J, Byquist AC, Crown A,Clifton DK, Hoffman GE, Ste<strong>in</strong>er RA, Tena-Sempere M,2007: Sexual differentiation of Kiss1 gene expression <strong>in</strong> thebra<strong>in</strong> of the rat. Endocr<strong>in</strong>ology 148, 1774–1783.K<strong>in</strong>oshita M, Tsukamura H, Adachi S, Matsui H, UenoyamaY, Iwata K, Yamada S, Inoue K, Ohtaki T, Matsumoto H,Maeda K, 2005: Involvement of central metast<strong>in</strong> <strong>in</strong> theregulation of preovulatory lute<strong>in</strong>iz<strong>in</strong>g hormone surge andestrous cyclicity <strong>in</strong> female rats. Endocr<strong>in</strong>ology 146, 4431–4436.Knobil E, 2005: Discovery of the hypothalamic gonadotrop<strong>in</strong>releas<strong>in</strong>ghormone pulse generator and of its physiologicsignificance. 1992. Am J Obstet Gynecol 193, 1765–1766.Kotani M, Detheux M, Vandenbogaerde A, Communi D,Vanderw<strong>in</strong>den JM, Le Poul E, Brezillon S, Tyldesley R,Suarez-Huerta N, Vandeput F, Blanpa<strong>in</strong> C, Schiffmann SN,Vassart G, Parmentier M, 2001: The metastasis suppressorgene KiSS-1 encodes kisspept<strong>in</strong>s, the natural ligands of theorphan G prote<strong>in</strong>-coupled receptor GPR54. J Biol Chem276, 34631–34636.Lee DK, Nguyen T, O’Neill GP, Cheng R, Liu Y, HowardAD, Coulombe N, Tan CP, Tang-Nguyen AT, George SR,O’Dowd BF, 1999: Discovery of a receptor related to thegalan<strong>in</strong> receptors. FEBS Lett 446, 103–107.Lents C, Barb C, 2007: Stimulatory actions of kisspept<strong>in</strong> ongonadotrop<strong>in</strong> secretion <strong>in</strong> prepubertal sw<strong>in</strong>e. Biol ReprodSpecial Issue 105 (Abstract No. 125).Maeda K, Adachi S, Inoue K, Ohkura S, Tsukamura H, 2007:Metast<strong>in</strong> ⁄ kisspept<strong>in</strong> and the control of estrous cycle <strong>in</strong> rats.Rev Endocr Metab Disord 8, 21–29.Matsui H, Takatsu Y, Kumano S, Matsumoto H, Ohtaki T,2004: Peripheral adm<strong>in</strong>istration of metast<strong>in</strong> <strong>in</strong>duces markedgonadotrop<strong>in</strong> release and ovulation <strong>in</strong> the rat. BiochemBiophys Res Commun 320, 383–388.Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D,Dixon J, Thresher RR, Mal<strong>in</strong>ge I, Lomet D, Carlton MB,Colledge WH, Caraty A, Aparicio SA, 2005: Kisspept<strong>in</strong>directly stimulates gonadotrop<strong>in</strong>-releas<strong>in</strong>g hormone releasevia G prote<strong>in</strong>-coupled receptor 54. Proc Natl Acad Sci USA102, 1761–1766.Moenter SM, Caraty A, Locatelli A, Karsch FJ, 1991: Patternof gonadotrop<strong>in</strong>-releas<strong>in</strong>g hormone (GnRH) secretion lead<strong>in</strong>gup to ovulation <strong>in</strong> the ewe: existence of a preovulatoryGnRH surge. Endocr<strong>in</strong>ology 129, 1175–1182.Muir AI, Chamberla<strong>in</strong> L, Elshourbagy NA, Michalovich D,Moore DJ, Calamari A, Szekeres PG, Sarau HM, ChambersJK, Murdock P, Steplewski K, Shabon U, Miller JE,Middleton SE, Darker JG, Larm<strong>in</strong>ie CG, Wilson S, BergsmaDJ, Emson P, Faull R, Philpott KL, Harrison DC, 2001:AXOR12, a novel human G prote<strong>in</strong>-coupled receptor,activated by the peptide KiSS-1. J Biol Chem 276, 28969–28975.Navarro VM, Castellano JM, Fernandez-Fernandez R,Barreiro ML, Roa J, Sanchez-Criado JE, Aguilar E,Dieguez C, P<strong>in</strong>illa L, Tena-Sempere M, 2004: Developmentaland hormonally regulated messenger ribonucleicacid expression of KiSS-1 and its putative receptor,GPR54, <strong>in</strong> rat hypothalamus and potent lute<strong>in</strong>iz<strong>in</strong>g hormone-releas<strong>in</strong>gactivity of KiSS-1 peptide. Endocr<strong>in</strong>ology145, 4565–4574.Navarro VM, Castellano JM, Fernandez-Fernandez R, TovarS, Roa J, Mayen A, Barreiro ML, Casanueva FF, Aguilar E,Dieguez C, P<strong>in</strong>illa L, Tena-Sempere M, 2005: Effects ofKiSS-1 peptide, the natural ligand of GPR54, on folliclestimulat<strong>in</strong>ghormone secretion <strong>in</strong> the rat. Endocr<strong>in</strong>ology146, 1689–1697.Ohtaki T, Sh<strong>in</strong>tani Y, Honda S, Matsumoto H, Hori A,Kanehashi K, Terao Y, Kumano S, Takatsu Y, Masuda Y,Ishibashi Y, Watanabe T, Asada M, Yamada T, SuenagaM, Kitada C, Usuki S, Kurokawa T, Onda H, Nishimura O,Fuj<strong>in</strong>o M, 2001: Metastasis suppressor gene KiSS-1 encodespeptide ligand of a G-prote<strong>in</strong>-coupled receptor. 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336 C Galli, I Lagutina, R Duchi, S
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Reprod Dom Anim 43 (Suppl. 2), 338-
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340 D Rath and LA JohnsonCommercial
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342 D Rath and LA JohnsonThe Commer
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344 D Rath and LA JohnsonX- and Y-b
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346 D Rath and LA JohnsonWalker SK,
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348 JM Vazquez, J Roca, MA Gil, C C
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350 JM Vazquez, J Roca, MA Gil, C C
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352 JM Vazquez, J Roca, MA Gil, C C
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354 JM Vazquez, J Roca, MA Gil, C C
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356 CBA Whitelaw, SG Lillico and T
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358 CBA Whitelaw, SG Lillico and T
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360 ACO Evans, N Forde, GM O’Gorm
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362 ACO Evans, N Forde, GM O’Gorm
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364 ACO Evans, N Forde, GM O’Gorm
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366 ACO Evans, N Forde, GM O’Gorm
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Reprod Dom Anim 43 (Suppl. 2), 368-
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370 JP Kastelic and JC Thundathilsp
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372 JP Kastelic and JC Thundathilme
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Reprod Dom Anim 43 (Suppl. 2), 374-
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376 GC AlthouseTable 1. Potential s
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378 GC Althousesemen to the domesti
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380 B Leboeuf, JA Delgadillo, E Man
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382 B Leboeuf, JA Delgadillo, E Man
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384 B Leboeuf, JA Delgadillo, E Man
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Reprod Dom Anim 43 (Suppl. 2), 386-
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388 N Kostereva and M-C HofmannFig.
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390 N Kostereva and M-C HofmannMMPs
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392 N Kostereva and M-C HofmannTado
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394 P Mermillod, R Dalbie` s-Tran,
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396 P Mermillod, R Dalbie` s-Tran,
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398 P Mermillod, R Dalbie` s-Tran,
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400 P Mermillod, R Dalbie` s-Tran,
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402 K Kikuchi, N Kashiwazaki, T Nag
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404 K Kikuchi, N Kashiwazaki, T Nag
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406 K Kikuchi, N Kashiwazaki, T Nag
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408 B ObackNumber of publications20
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410 B ObackReprogramming Ability of
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412 B Obackstudies have shown that
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414 B ObackFig. 4. Climbing mount e
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416 B ObackRenard JP, Maruotti J, J
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418 P Loi, K Matzukawa, G Ptak, Y N
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420 P Loi, K Matzukawa, G Ptak, Y N
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422 P Loi, K Matzukawa, G Ptak, Y N
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Table of Contents Volume 43 · Supp