Discovery and evolutionary history of gonadotrophin-inhibitory hormone and kisspeptin: new key neuropeptides controlling reproduction.
Gonadotrophin-releasing hormone (GnRH) is the primary hypothalamic factor responsible for the control of gonadotrophin secretion in vertebrates. However, within the last decade, two other hypothalamic neuropeptides have been found to play key roles in the control of reproductive functions: gonadotrophin-inhibitory hormone (GnIH) and kisspeptin. In 2000, we discovered GnIH in the quail hypothalamus. GnIH inhibits gonadotrophin synthesis and release in birds through actions on GnRH neurones and gonadotrophs, mediated via GPR147. Subsequently, GnIH orthologues were identified in other vertebrate species from fish to humans. As in birds, mammalian and fish GnIH orthologues inhibit gonadotrophin release, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal axis across species. Subsequent to the discovery of GnIH, kisspeptin, encoded by the KiSS-1 gene, was discovered in mammals. By contrast to GnIH, kisspeptin has a direct stimulatory effect on GnRH neurones via GPR54. GPR54 is also expressed in pituitary cells, but whether gonadotrophs are targets for kisspeptin remains unresolved. The KiSS-1 gene is also highly conserved and has been identified in mammals, amphibians and fish. We have recently found a second isoform of KiSS-1, designated KiSS-2, in several vertebrates, but not birds, rodents or primates. In this review, we highlight the discovery, mechanisms of action, and functional significance of these two chief regulators of the reproductive axis.
Tsutsui
K
K
Department of Biology, Waseda University, Tokyo, Japan. k-tsutsui@waseda.jp
Bentley
G E
GE
Kriegsfeld
L J
LJ
Osugi
T
T
Seong
J Y
JY
Vaudry
H
H
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D006023:Glycoproteins / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D006062:Gonadotropins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012098:Reproduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D006023:Glycoproteins; D006062:Gonadotropins; D009479:Neuropeptides; C416987:RFamide peptide; D043562:Receptors, G-Protein-Coupled; D025521:Tumor Suppressor Proteins; C014995:gonadotropin inhibitor; D007987:Gonadotropin-Releasing Hormone
Proc Natl Acad Sci U S A. 1972 Jan;69(1):278-82
4550508
J Biol Chem. 1982 Sep 25;257(18):10722-8
7050118
Trends Neurosci. 2007 Oct;30(10):504-11
17904653
Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2410-5
16467147
Endocrinology. 2009 Jun;150(6):2799-804
19131572
Gen Comp Endocrinol. 2008 May 1;156(3):552-8
18405899
Gen Comp Endocrinol. 2008 Mar 1;156(1):34-43
18031743
Mass Spectrom Rev. 2005 Jul-Aug;24(4):469-86
15389843
N Engl J Med. 2003 Oct 23;349(17):1614-27
14573733
Endocrinology. 2008 Oct;149(10):4958-69
18566114
Biochem Biophys Res Commun. 2000 Aug 28;275(2):661-7
10964719
Prog Brain Res. 1992;92:25-37
1302879
FEBS J. 2006 Apr;273(8):1731-43
16623709
J Endocrinol. 2002 Sep;174(3):395-402
12208659
Microsc Res Tech. 2001 Aug 1;54(3):158-72
11458399
J Neuroendocrinol. 2004 Oct;16(10):850-8
15500545
Nature. 1983 Sep 22-28;305(5932):328-30
6137771
Peptides. 1988 Jul-Aug;9(4):915-22
3067224
Prog Neurobiol. 2009 May;88(1):76-88
19428963
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):3052-7
15708982
Endocrinology. 2009 Jun;150(6):2837-46
19164475
Biochem Biophys Res Commun. 2004 Jul 23;320(2):383-8
15219839
Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1761-6
15665093
J Biol Chem. 2001 Sep 14;276(37):34631-6
11457843
Biochim Biophys Acta. 2001 Sep 26;1540(3):221-32
11583817
Endocrinology. 2006 Dec;147(12):5817-25
16959837
J Neuroendocrinol. 2008 Sep;20(9):1078-88
18638025
Proc Natl Acad Sci U S A. 1984 Jun;81(12):3874-8
6427779
Gen Comp Endocrinol. 2010 May 1;166(3):565-72
20074575
Endocrinology. 2009 Feb;150(2):821-31
18927220
Biochem Biophys Res Commun. 1971 Jun 18;43(6):1334-9
4936338
Endocrinology. 2008 Sep;149(9):4387-95
18511511
J Exp Zool A Comp Exp Biol. 2006 Sep 1;305(9):801-6
16902951
Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2129-34
15684075
J Endocrinol. 2004 Jul;182(1):33-42
15225129
Endocrinology. 2007 Mar;148(3):1150-7
17185374
J Neurosci. 2005 Dec 7;25(49):11349-56
16339030
Endocrinology. 2008 Jan;149(1):268-78
17901228
Brain Behav Evol. 2008;71(2):127-42
18032888
Gen Comp Endocrinol. 2010 Jun 1;167(2):331-7
20350548
Biochim Biophys Acta. 2003 Feb 17;1593(2-3):151-7
12581859
Horm Behav. 2006 Apr;49(4):550-5
16460739
Endocrinology. 2009 Mar;150(3):1413-20
19008316
J Endocrinol. 1985 Dec;107(3):317-24
4067487
Biochim Biophys Acta. 2004 May 25;1678(2-3):102-10
15157736
Endocrinology. 2010 Jan;151(1):271-80
19952272
Gen Comp Endocrinol. 1984 Oct;56(1):70-81
6489741
Neuroendocrinology. 2004;80(4):264-72
15665556
Eur J Biochem. 2002 Dec;269(24):6000-8
12473095
Endocrinology. 2005 Apr;146(4):1689-97
15637288
Peptides. 2006 May;27(5):1121-9
16517011
Peptides. 2009 Jan;30(1):123-9
18948153
J Biol Chem. 1986 Apr 15;261(11):4812-9
3514603
J Neuroendocrinol. 2010 Feb;22(2):110-8
20002963
Cancer Res. 1997 Jun 15;57(12):2384-7
9192814
Endocrinology. 2004 Sep;145(9):4073-7
15217982
Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10714-9
17563351
Endocrinology. 2009 Dec;150(12):5549-56
19808777
Peptides. 2009 Jan;30(1):26-33
18840491
Comp Biochem Physiol C Toxicol Pharmacol. 2003 Feb;134(2):259-66
12600686
Nat Cell Biol. 2000 Oct;2(10):703-8
11025660
J Comp Neurol. 2002 Jun 24;448(2):111-27
12012424
Science. 1977 Aug 12;197(4304):670-1
877582
Peptides. 2009 Jan;30(1):94-102
18789989
Ann N Y Acad Sci. 2010 Jul;1200:67-74
20633134
Proc Natl Acad Sci U S A. 1983 May;80(9):2794-8
6341999
Endocrinology. 2002 Feb;143(2):411-9
11796493
J Neuroendocrinol. 2004 Dec;16(12):999-1006
15667455
Anim Reprod Sci. 2008 Jan 30;103(3-4):360-5
17604578
Gen Comp Endocrinol. 2007 Aug-Sep;153(1-3):365-70
17141777
J Endocrinol. 2005 Jan;184(1):257-66
15642802
J Endocrinol. 2008 Oct;199(1):105-12
18653621
Peptides. 2008 Jan;29(1):57-64
18045739
J Endocrinol. 2009 Jun;201(3):407-18
19304758
Endocrinology. 2004 Oct;145(10):4565-74
15242985
Gen Comp Endocrinol. 2006 Dec;149(3):226-35
16876798
Trends Endocrinol Metab. 2010 Apr;21(4):255-60
20060314
J Reprod Dev. 2005 Jun;51(3):359-77
15812141
Biochem Biophys Res Commun. 1982 Aug;107(3):820-7
6814432
Peptides. 2009 Jan;30(1):171-9
18550222
Peptides. 1985;6 Suppl 3:333-7
3913911
Nature. 2001 May 31;411(6837):613-7
11385580
Cancer Res. 2002 Oct 1;62(19):5399-404
12359743
Endocrinology. 2008 Nov;149(11):5811-21
18617613
J Endocrinol. 2006 Mar;188(3):417-23
16522722
J Comp Neurol. 2009 Dec 20;517(6):841-55
19844991
J Chem Neuroanat. 2008 Dec;36(3-4):131-7
18761083
J Neuroendocrinol. 2003 Aug;15(8):794-802
12834441
PLoS One. 2009 Dec 22;4(12):e8400
20027225
Biochem J. 2001 Mar 1;354(Pt 2):379-85
11171117
Endocrinology. 2008 Nov;149(11):5770-82
18617612
Horm Behav. 2007 Jan;51(1):171-80
17113584
FEBS Lett. 2002 Feb 13;512(1-3):255-8
11852091
Mol Cell Endocrinol. 2009 Nov 27;312(1-2):61-71
19084576
Front Neuroendocrinol. 2010 Jul;31(3):284-95
20211640
Curr Biol. 2006 Sep 5;16(17):1730-5
16950111
Reproduction. 2008 Feb;135(2):267-74
18239054
Endocrinology. 2008 May;149(5):2467-76
18202129
Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10972-6
12944565
Peptides. 2009 Jan;30(1):154-63
18838092
Endocrinology. 2006 Mar;147(3):1187-94
16293662
J Natl Cancer Inst. 1996 Dec 4;88(23):1731-7
8944003
J Neuroendocrinol. 2007 Jul;19(7):521-30
17532794
Peptides. 2010 Jun;31(6):1034-43
20226824
Cell Tissue Res. 2003 Apr;312(1):73-9
12712318
J Biol Chem. 2001 Aug 3;276(31):28969-75
11387329
J Endocrinol. 2003 Aug;178(2):311-8
12904178
Endocrinology. 2003 Sep;144(9):3879-84
12933661
J Neuroendocrinol. 2010 Apr;22(4):309-16
20136694