GnRH signaling, the gonadotrope and endocrine control of fertility.
Mammalian reproductive cycles are controlled by an intricate interplay between the hypothalamus, pituitary and gonads. Central to the function of this axis is the ability of the pituitary gonadotrope to appropriately respond to stimulation by gonadotropin-releasing hormone (GnRH). This review focuses on the role of cell signaling and in particular, mitogen-activated protein kinase (MAPK) activities regulated by GnRH that are necessary for normal fertility. Recently, new mouse models making use of conditional gene deletion have shed new light on the relationships between GnRH signaling and fertility in both male and female mice. Within the reproductive axis, GnRH signaling is initiated through discrete membrane compartments in which the receptor resides leading to the activation of the extracellular signal-regulated kinases (ERKs 1/2). As defined by gonadotrope-derived cellular models, the ERKs appear to play a central role in the regulation of a cohort of immediate early genes that regulate the expression of late genes that, in part, define the differentiated character of the gonadotrope. Recent data would suggest that in vivo, conditional, pituitary-specific disruption of ERK signaling by GnRH leads to a gender-specific perturbation of fertility. Double ERK knockout in the anterior pituitary leads to female infertility due to LH biosynthesis deficiency and a failure in ovulation. In contrast, male mice are modestly LH deficient; however, this does not have an appreciable impact on fertility.
Bliss
Stuart P
SP
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States.
Navratil
Amy M
AM
Xie
Jianjun
J
Roberson
Mark S
MS
D000818:Animals; D004703:Endocrine System / Q000502:physiology; D005260:Female; D005298:Fertility / Q000502:physiology*; D052681:Gonadotrophs / Q000378:metabolism / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism* / Q000502:physiology; D006066:Gonads / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology
D007987:Gonadotropin-Releasing Hormone
Am J Physiol Cell Physiol. 2006 Jul;291(1):C1-10
16769815
J Biol Chem. 2001 Feb 16;276(7):4554-63
11083862
Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12280-4
8618885
J Biol Chem. 2003 Nov 21;278(47):47307-18
12963732
Trends Endocrinol Metab. 2003 Jan;14(1):35-43
12475610
N Engl J Med. 1997 Nov 27;337(22):1597-602
9371856
J Clin Endocrinol Metab. 2008 Jul;93(7):2686-92
18445673
J Clin Endocrinol Metab. 2008 Mar;93(3):758-63
18160472
FEBS Lett. 2005 Jun 13;579(15):3271-7
15943972
Endocrinology. 2003 Jun;144(6):2409-16
12746302
Anim Reprod Sci. 2005 Aug;88(1-2):57-74
15993012
Mol Cell. 2004 Apr 9;14(1):43-55
15068802
Endocrinology. 1998 Jun;139(6):2710-7
9607776
J Biol Chem. 2001 Mar 16;276(11):7754-61
11112780
Mol Endocrinol. 2009 Jul;23(7):1092-101
19372235
Cell. 2002 Apr 19;109(2):217-28
12007408
Endocr Rev. 1997 Apr;18(2):180-205
9101136
J Biol Chem. 1998 Jul 17;273(29):17979-82
9660746
Endocrinology. 1999 Feb;140(2):827-34
9927312
J Biol Chem. 2004 Nov 12;279(46):47929-38
15337756
Endocrinology. 1994 Sep;135(3):876-80
8070381
Proc Natl Acad Sci U S A. 2007 May 8;104(19):8173-7
17470805
Endocr J. 2009;56(6):729-37
19609045
J Biol Chem. 1998 May 8;273(19):11472-7
9565559
Endocrinology. 2008 Nov;149(11):5577-91
18653705
J Clin Invest. 2000 Apr;105(7):853-4
10749562
J Biol Chem. 2006 Jan 13;281(2):1261-73
16280323
J Neurosci. 2008 Aug 27;28(35):8691-7
18753370
Endocrinology. 1988 Aug;123(2):1119-27
2899500
J Neuroendocrinol. 2006 Oct;18(10):806-9
16965299
J Biol Chem. 1997 Dec 19;272(51):32642-8
9405481
Dev Dyn. 1999 May;215(1):26-44
10340754
Biol Reprod. 1998 Aug;59(2):278-83
9687296
J Biol Chem. 2002 Oct 4;277(40):37469-78
12145309
Neuroendocrinology. 2002 Dec;76(6):357-65
12566943
J Clin Endocrinol Metab. 2000 Sep;85(9):3002-8
10999776
Brain Res Rev. 2008 Mar;57(2):277-87
17604108
J Biol Chem. 1999 Oct 15;274(42):30146-53
10514504
Science. 2000 Nov 24;290(5496):1574-7
11090355
Mol Cell Endocrinol. 2003 Aug 29;206(1-2):93-111
12943993
Mol Cell Biol. 1995 Jul;15(7):3531-9
7791760
J Biol Chem. 1996 Sep 27;271(39):23711-7
8798594
J Clin Endocrinol Metab. 2002 Oct;87(10):4825-8
12364481
Endocrinology. 2008 Jan;149(1):20-7
17947360
Mol Cell Endocrinol. 2010 Jan 27;314(2):192-203
19747958
J Clin Endocrinol Metab. 1984 Aug;59(2):328-37
6429184
Am J Physiol Cell Physiol. 2009 Sep;297(3):C591-600
19587220
Endocrinology. 1994 Sep;135(3):1165-70
8070359
J Biol Chem. 2001 Dec 7;276(49):45604-13
11591707
Neuron. 2002 May 30;34(5):807-20
12062026
Endocrinology. 2006 Dec;147(12):5817-25
16959837
Mol Pharmacol. 1994 Jul;46(1):1-7
8058044
Trends Endocrinol Metab. 2006 May-Jun;17(4):159-65
16595179
Endocrinology. 2008 Aug;149(8):4168-76
18467444
Neuron. 2006 Oct 19;52(2):271-80
17046690
Science. 1986 Dec 12;234(4782):1372-8
3097822
Biol Reprod. 2001 Mar;64(3):735-42
11207186
Endocr Rev. 2001 Apr;22(2):153-83
11294822
Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1886-90
7892195
Annu Rev Biophys Biomol Struct. 2004;33:269-95
15139814
Mol Cell Endocrinol. 2002 Jun 14;191(2):149-56
12062898
Biol Reprod. 2003 Dec;69(6):1771-8
12890720
Neuroendocrinology. 2003 Jul;78(1):29-35
12869797
J Cell Sci. 2006 Nov 15;119(Pt 22):4607-15
17093265
J Biol Chem. 2005 Aug 19;280(33):29796-803
15967801
Science. 1978 Nov 10;202(4368):631-3
100883
Mol Endocrinol. 2001 Mar;15(3):390-7
11222740
Science. 1996 Aug 30;273(5279):1219-21
8703054
J Biol Chem. 1999 Jul 9;274(28):19639-43
10391901
J Biol Chem. 1996 Aug 16;271(33):20024-8
8702720
Mol Cell Endocrinol. 1999 May 25;151(1-2):129-36
10411327
Pflugers Arch. 2000;439(3 Suppl):R19-20
10653128
Eur J Endocrinol. 2000 May;142(5):537-44
10802535
Endocrinology. 1998 Oct;139(10):4092-101
9751487
Endocrinology. 2005 Jul;146(7):2976-84
15831567
J Mol Med (Berl). 2004 Nov;82(11):725-34
15365636
Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7794-8
8356086
Mol Endocrinol. 2005 Oct;19(10):2624-38
15961508
Nature. 2000 Mar 23;404(6776):411-4
10746731
Endocrinology. 1973 Aug;93(2):385-90
4736992
BMC Neurosci. 2008 Dec 03;9 Suppl 2:S12
19090985
J Endocrinol. 1986 Oct;111(1):43-9
3097234
J Biol Chem. 2006 Feb 3;281(5):2701-10
16314413
Anim Reprod Sci. 2005 Aug;88(1-2):5-28
16140177
Mol Endocrinol. 2008 Oct;22(10):2322-35
18635666
Mol Cell Endocrinol. 2010 Jan 27;314(2):204-12
19481581
Biol Reprod. 2009 Sep;81(3):465-72
19458315
Curr Pharm Des. 2006;12(14):1683-702
16712482
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13612-7
9811848
Mol Endocrinol. 2007 May;21(5):1216-33
17327421
J Biol Chem. 2000 Aug 18;275(33):25342-50
10840035
J Biol Chem. 2001 Oct 26;276(43):39685-94
11495905
Endocrinology. 2007 Mar;148(3):1150-7
17185374
Dev Cell. 2004 Jul;7(1):33-44
15239952
Biochem Soc Trans. 1993 Nov;21(4):357S
8131937
Endocrinology. 1996 Jan;137(1):304-11
8536629
EMBO J. 2002 Apr 2;21(7):1628-37
11927547
Mol Endocrinol. 1999 May;13(5):752-63
10319325
Nat Cell Biol. 2000 Feb;2(2):110-6
10655591
Neuroendocrinology. 1996 Feb;63(2):120-31
9053776
Front Neuroendocrinol. 2009 Jan;30(1):10-29
18708085
Neuroendocrinology. 2004;80(4):264-72
15665556
Mol Endocrinol. 1992 Oct;6(10):1673-81
1333052
J Biol Chem. 1999 Oct 8;274(41):28880-6
10506131
J Clin Endocrinol Metab. 1994 Jun;78(6):1521-4
8200957
Mol Cell Endocrinol. 1988 Jul;58(1):1-8
3208985
Oncogene. 2007 May 14;26(22):3291-310
17496923
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2969-74
12591945
Science. 1998 Jan 9;279(5348):227-30
9422695
Mol Cell Endocrinol. 2003 Dec 30;212(1-2):19-27
14654247
Growth Factors. 2006 Mar;24(1):21-44
16393692
Mol Hum Reprod. 2009 Feb;15(2):77-87
19106114
Genesis. 2008 Oct;46(10):507-14
18802953
EMBO J. 2000 Jun 15;19(12):2911-23
10856236
Mol Endocrinol. 2006 Nov;20(11):2909-30
16772531
Mol Endocrinol. 1999 Apr;13(4):566-77
10194763
Annu Rev Biophys Biomol Struct. 2003;32:257-83
12543707
Nature. 1991 Oct 10;353(6344):529-36
1922361
Mol Endocrinol. 1997 Jun;11(6):738-46
9171237
Mol Endocrinol. 2005 Sep;19(9):2412-23
15890671
Mol Endocrinol. 2007 Dec;21(12):3071-86
17823303
J Biol Chem. 1996 Aug 30;271(35):21187-92
8702889
Cell Mol Neurobiol. 1998 Feb;18(1):125-46
9524733
Neuroendocrinology. 1983 May;36(5):376-84
6406927
Mol Cell Endocrinol. 2001 Jun 20;179(1-2):33-7
11420128
Prog Clin Biol Res. 1982;112 Pt A:165-82
6761698
J Biol Chem. 2001 May 25;276(21):18066-74
11278484
Recent Prog Horm Res. 2000;55:1-13; discussion 13-4
11036930
Biol Reprod. 2008 Nov;79(5):947-53
18716286
Mol Endocrinol. 1994 Oct;8(10):1420-33
7531821
J Neuroendocrinol. 2009 Mar;21(4):305-11
19207812
Sex Dev. 2008;2(4-5):181-93
18987492
Endocrinology. 2001 Feb;142(2):573-9
11159827
Neuroendocrinology. 1984 Sep;39(3):267-74
6438545
Science. 1990 Feb 16;247(4944):836-8
2106159
J Endocrinol Invest. 1998 Oct;21(9):602-11
9856414
Cell Signal. 2007 Jul;19(7):1383-92
17524618
Science. 1993 Apr 2;260(5104):82-4
8385366
J Cell Physiol. 2007 Dec;213(3):589-602
17786953
Endocr Metab Immune Disord Drug Targets. 2009 Jun;9(2):145-50
19519464
Endocrinology. 2004 Aug;145(8):3594-602
15059960
Endocrinology. 1998 Jul;139(7):3104-11
9645682
Endocrinology. 1988 Jun;122(6):2570-7
3286227
Endocrinology. 1995 Aug;136(8):3604-10
7628399
Endocrinology. 1988 Apr;122(4):1282-90
3126034
J Biol Chem. 2001 Feb 2;276(5):3123-9
11069921
N Engl J Med. 1997 Aug 28;337(9):607-11
9271483
Semin Reprod Med. 2007 Sep;25(5):368-78
17710733
J Biol Chem. 1999 May 14;274(20):13870-6
10318795
Endocrinology. 2000 Jan;141(1):299-306
10614651
J Endocrinol. 1994 Feb;140(2):R15-8
8169550
Adv Enzyme Regul. 2010;50(1):285-307
19895837
Mol Endocrinol. 2007 Feb;21(2):538-49
17068198
Cell. 1998 May 15;93(4):605-15
9604935
Am J Physiol Regul Integr Comp Physiol. 2001 Dec;281(6):R1975-85
11705784
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12759-64
14566055
Mol Endocrinol. 2008 Jun;22(6):1295-303
18218726
Biochem Biophys Res Commun. 1986 Jan 29;134(2):565-71
3511906
Endocrinology. 1987 Jul;121(1):182-9
3297635
Science. 1986 Dec 12;234(4782):1366-71
3024317
Endocrinology. 2003 Jan;144(1):138-45
12488339
Endocrinology. 1976 Jul;99(1):243-8
820547
Endocrinology. 1948 Dec;43(6):389-405
18100247
J Immunol. 2008 Jun 15;180(12):8192-203
18523285
Endocrinology. 1985 Jan;116(1):142-7
3964745
J Biol Chem. 2003 Feb 21;278(8):6258-67
12473660
Endocrinology. 2000 May;141(5):1795-803
10803590
J Clin Endocrinol Metab. 1985 Nov;61(5):851-8
3900122
Mol Endocrinol. 1992 Jul;6(7):1163-9
1324422
J Biol Chem. 1996 Aug 9;271(32):19443-50
8702633
Biol Reprod. 2009 Dec;81(6):1206-15
19710510
Endocrinology. 2007 Oct;148(10):4927-36
17595229
Endocrinology. 2008 Jun;149(6):2701-11
18325995
Oncogene. 2000 Dec 27;19(56):6594-9
11426644
Mol Cell Endocrinol. 2006 Jun 27;252(1-2):184-90
16682115
Endocrinology. 1997 Dec;138(12):5408-14
9389526
Recent Prog Horm Res. 1991;47:155-87; discussion 188-9
1745819
Physiol Rev. 2007 Jul;87(3):933-63
17615393
Cancer Res. 2004 Oct 15;64(20):7533-44
15492280
Mol Endocrinol. 1996 Apr;10(4):356-66
8721981
Curr Opin Endocrinol Diabetes Obes. 2007 Aug;14(4):306-10
17940457
Tissue Cell. 2001 Aug;33(4):361-7
11521952
Science. 2009 May 15;324(5929):938-41
19443782
Neuroendocrinology. 1999 Oct;70(4):246-54
10529619
Biochemistry. 2000 Jul 18;39(28):8133-41
10889019
Cell. 1995 Jan 27;80(2):179-85
7834738
Genes Dev. 1994 Oct 1;8(19):2302-12
7958897
J Biol Chem. 2003 Aug 22;278(34):31593-602
12791688
Biol Reprod. 2001 Dec;65(6):1789-93
11717142
Endocrinology. 1996 Jul;137(7):3144-7
8770941
N Engl J Med. 1986 Dec 4;315(23):1459-68
3097540
J Cell Sci. 2002 Feb 1;115(Pt 3):455-65
11861753
J Biol Chem. 1994 Mar 18;269(11):7851-4
8132501
Science. 1982 Feb 19;215(4535):983-5
6296998
Recent Prog Horm Res. 1980;36:53-88
6774388
Endocrinology. 1991 Jan;128(1):509-17
1702704
Mol Endocrinol. 1996 Apr;10(4):439-50
8721988
J Biol Chem. 1995 Oct 20;270(42):25259-65
7559665
Endocrinology. 2005 Dec;146(12):5503-13
16141398
Biochem Soc Trans. 2006 Nov;34(Pt 5):842-5
17052211
Endocrinology. 2007 Feb;148(2):782-9
17095591
Biol Reprod. 2002 Jul;67(1):119-25
12080007
Development. 2001 Jan;128(2):147-54
11124111
Reprod Sci. 2007 Feb;14(2):101-16
17636222
J Endocrinol. 1999 Sep;162(3):R1-5
10467239
Endocrinology. 1992 Apr;130(4):2101-5
1312442
J Steroid Biochem Mol Biol. 1996 Jan;56(1-6 Spec No):67-77
8603049
Nature. 2000 Apr 13;404(6779):770-4
10783891
Endocrinology. 1999 Jan;140(1):165-70
9886822
Genesis. 2006 Sep;44(9):419-24
16937416
J Comp Neurol. 1999 Aug 23;411(2):346-58
10404258
Nature. 1992 Jul 16;358(6383):242-5
1321347
Annu Rev Cell Dev Biol. 2003;19:91-118
14570565
J Leukoc Biol. 2007 Apr;81(4):860-9
17289800
Endocrinology. 2002 Mar;143(3):985-97
11861523
Endocrinology. 2003 Jul;144(7):2768-74
12810529
Biol Reprod. 1986 Dec;35(5):1154-61
3103699
FEBS J. 2008 Nov;275(22):5479-95
18959738
Endocrinology. 2000 Apr;141(4):1477-85
10746653
J Biol Chem. 2000 Mar 31;275(13):9193-200
10734055
Horm Res. 2009;71(2):75-82
19129711
Endocrinology. 2000 Dec;141(12):4564-75
11108269
Endocrinology. 1989 Aug;125(2):917-24
2502379
Genes Dev. 2002 Feb 15;16(4):427-38
11850406
Mol Cell Endocrinol. 1998 Jul 25;142(1-2):99-117
9783907
Curr Biol. 2005 Jul 26;15(14):1319-24
16051177
Biol Reprod. 1985 May;32(4):855-64
3924134
Peptides. 2009 Jan;30(1):111-22
18614256
Mol Endocrinol. 2001 Jan;15(1):172-83
11145748
Mol Endocrinol. 2005 Jan;19(1):237-54
15375186
Mol Endocrinol. 2001 Jan;15(1):184-200
11145749
J Mol Endocrinol. 2005 Aug;35(1):177-89
16087731
Nature. 1993 Jul 15;364(6434):249-52
8321321
EMBO J. 1999 Feb 1;18(3):664-74
9927426
Neuroendocrinology. 2008;87(3):142-50
18063854
Mol Endocrinol. 1991 Mar;5(3):347-55
1653891
J Biol Chem. 1992 Oct 25;267(30):21281-4
1328228
Mol Cell Biochem. 1999 Dec;202(1-2):85-90
10705998
Genesis. 2009 Jan;47(1):55-60
19039787
J Endocrinol. 1989 Oct;123(1):1-2
2681501
Endocrinology. 1999 Mar;140(3):1310-8
10067858
Endocrinol Jpn. 1991 Aug;38(4):383-91
1802679
Endocrinology. 2004 Dec;145(12):5832-9
15319358
Nat Genet. 1997 Feb;15(2):201-4
9020850
Mol Endocrinol. 2002 Feb;16(2):221-33
11818496
Gen Comp Endocrinol. 2008 Apr 1;156(2):426-33
18275963
Mol Endocrinol. 1998 Jun;12(6):815-24
9626657
Mol Cell Endocrinol. 1996 Apr 19;118(1-2):103-11
8735596
Endocrinology. 1997 Dec;138(12):5227-30
9389505
Mol Endocrinol. 2002 Mar;16(3):419-34
11875099
Mol Cell Biol. 2001 May;21(9):2981-90
11287604
J Biol Chem. 2002 Mar 15;277(11):9429-36
11777902
Semin Reprod Med. 2004 Aug;22(3):253-67
15319828
Oncogene. 2004 Jan 29;23(4):991-9
14647423
Mol Endocrinol. 2001 May;15(5):695-703
11328852
Biol Reprod. 1981 Jun;24(5):1145-55
6268204
Biol Reprod. 2002 Sep;67(3):725-34
12193378
Trends Genet. 1998 Jul;14(7):284-90
9676531
Mol Endocrinol. 2009 Apr;23(4):510-9
19179479
J Mol Endocrinol. 2006 Feb;36(1):41-50
16461925
J Membr Biol. 1998 Jul 15;164(2):103-14
9662555
Cell Calcium. 2006 Nov-Dec;40(5-6):405-12
17030366
J Biol. 2006;5(5):14
16805921
Mol Cell Endocrinol. 1995 Feb;107(2):241-5
7768336
Mol Cell Endocrinol. 2009 Sep 24;308(1-2):17-25
19549588
Endocrinology. 2008 Jun;149(6):3118-29
18356273
Fertil Steril. 2005 Feb;83(2):466-70
15705395
J Clin Endocrinol Metab. 2003 Feb;88(2):834-43
12574221
Front Biosci. 1998 Nov 01;3:D1134-47
9792904
Genesis. 2006 Aug;44(8):391-5
16868919
Biochem J. 1983 Jul 15;214(1):11-9
6311174
Nat Genet. 2003 Apr;33(4):463-5
12627230
Endocr Rev. 1994 Aug;15(4):462-99
7988482
Endocrinology. 1993 Jun;132(6):2307-11
8504735
J Biol Chem. 2004 Jan 2;279(1):152-62
14570911
Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2449-54
11226259
Gynecol Endocrinol. 2005 Apr;20(4):188-94
16019360
Biochem Biophys Res Commun. 1992 Oct 30;188(2):921-6
1445333
Mol Endocrinol. 2006 Jun;20(6):1366-77
16543408
Endocrinology. 2009 Aug;150(8):3833-44
19423765
Nat Cell Biol. 2002 Aug;4(8):556-64
12134156
Neuroendocrinology. 2002 Jun;75(6):392-401
12065892
J Neuroendocrinol. 1998 Jun;10(6):461-71
9688349
J Biol Chem. 1999 Oct 15;274(42):29796-804
10514457
J Immunol. 2005 Aug 15;175(4):2374-80
16081808
Biol Reprod. 2006 Jun;74(6):993-8
16481592
Mol Endocrinol. 2007 May;21(5):1175-91
17299135
PLoS One. 2009 Sep 29;4(9):e7244
19787048
Endocr Rev. 2000 Oct;21(5):551-83
11041448
J Biol Chem. 2001 Feb 9;276(6):4416-23
11054417
Science. 1973 Feb 2;179(4072):484-6
4196168
Endocrinology. 1997 Apr;138(4):1673-82
9075730
Mol Endocrinol. 1990 Apr;4(4):597-603
1704103
Mol Cell Endocrinol. 2003 Jul 31;205(1-2):51-64
12890567
J Biol Chem. 2002 Aug 30;277(35):32099-108
12050161
Gynecol Endocrinol. 2008 Jan;24(1):4-11
18224538
J Biol Chem. 2003 Sep 5;278(36):34418-26
12821670
Biophys J. 2006 Jul 1;91(1):74-83
16603486
Neuroendocrinology. 1992 Aug;56(2):214-24
1407376
Mol Endocrinol. 1998 Feb;12(2):161-71
9482659
Endocrinology. 2008 Mar;149(3):1415-22
18039780
J Biol Chem. 2001 Dec 14;276(50):47195-201
11581274
Endocrinology. 2003 Oct;144(10):4484-91
12960084
Trends Endocrinol Metab. 2000 Apr;11(3):91-9
10707049
Endocrinology. 1986 Jun;118(6):2608-10
3084224
Nat Genet. 1998 Jan;18(1):14-5
9425890
Endocrinology. 2006 Dec;147(12):6036-45
16935846
Circ Res. 2004 Apr 30;94(8):1133-41
15031261
J Biol Chem. 2000 May 12;275(19):14182-9
10799494
Endocrinology. 1994 Jul;135(1):315-20
8013367
Endocrinology. 2003 Oct;144(10):4354-65
12960037
Mol Endocrinol. 2002 Jul;16(7):1638-51
12089357