title: Delayed puberty but normal fertility in mice with selective deletion of insulin receptors from Kiss1 cells.
abstract: Pubertal onset only occurs in a favorable, anabolic hormonal environment. The neuropeptide kisspeptin, encoded by the Kiss1 gene, modifies GnRH neuronal activity to initiate puberty and maintain fertility, but the factors that regulate Kiss1 neurons and permit pubertal maturation remain to be clarified. The anabolic factor insulin may signal nutritional status to these neurons. To determine whether insulin sensing plays an important role in Kiss1 neuron function, we generated mice lacking insulin receptors in Kiss1 neurons (IR(ΔKiss) mice). IR(ΔKiss) females showed a delay in vaginal opening and in first estrus, whereas IR(ΔKiss) males also exhibited late sexual maturation. Correspondingly, LH levels in IR(ΔKiss) mice were reduced in early puberty in both sexes. Adult reproductive capacity, body weight, fat composition, food intake, and glucose regulation were comparable between the 2 groups. These data suggest that impaired insulin sensing by Kiss1 neurons delays the initiation of puberty but does not affect adult fertility. These studies provide insight into the mechanisms regulating pubertal timing in anabolic states.
authors: Center for Diabetes and Endocrine Research, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors: Xiaoliang
authors: X
authors: Qiu
authors: Abigail R
authors: AR
authors: Dowling
authors: Joseph S
authors: JS
authors: Marino
authors: Latrice D
authors: LD
authors: Faulkner
authors: Benjamin
authors: B
authors: Bryant
authors: Jens C
authors: JC
authors: Brüning
authors: Carol F
authors: CF
authors: Elias
authors: Jennifer W
authors: JW
authors: Hill
mesh_terms: D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D025461:Feedback, Physiological; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology; D007328:Insulin / Q000502:physiology; D059648:Kisspeptins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007986:Luteinizing Hormone / Q000502:physiology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D011628:Puberty, Delayed / Q000235:genetics / Q000503:physiopathology*; D011972:Receptor, Insulin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012741:Sexual Maturation / Q000235:genetics / Q000502:physiology
chemical_list: D007328:Insulin; C491407:Kiss1 protein, mouse; D059648:Kisspeptins; C074283:estradiol 3-benzoate; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D011972:Receptor, Insulin
references: Am J Physiol Endocrinol Metab. 2008 May;294(5):E827-32
references: 18285524
references: Endocrinology. 2011 Apr;152(4):1541-50
references: 21325051
references: J Clin Invest. 2011 Feb;121(2):604-12
references: 21245576
references: Nature. 1979 Nov 29;282(5738):503-5
references: 116135
references: Endocrinology. 2005 Sep;146(9):3917-25
references: 15932928
references: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10972-6
references: 12944565
references: J Clin Invest. 2010 Aug;120(8):2900-9
references: 20628204
references: Neurosci Lett. 2009 Aug 28;460(2):143-7
references: 19477231
references: Mol Cell. 1998 Nov;2(5):559-69
references: 9844629
references: Mol Cell Endocrinol. 2007 May 30;270(1-2):64-72
references: 17379398
references: N Engl J Med. 2003 Oct 23;349(17):1614-27
references: 14573733
references: Diabetes Care. 2012 Mar;35(3):536-41
references: 22279034
references: Neuroendocrinology. 2009;89(2):131-9
references: 18832802
references: J Neurosci. 2010 Feb 17;30(7):2472-9
references: 20164331
references: J Neuroendocrinol. 2006 Apr;18(4):298-303
references: 16503925
references: Biol Reprod. 2009 Dec;81(6):1093-8
references: 19605781
references: Endocrinology. 2010 Feb;151(2):722-30
references: 19952274
references: Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22693-8
references: 21149719
references: Nat Rev Endocrinol. 2011 Sep 13;8(1):40-53
references: 21912400
references: Biol Reprod. 1993 Mar;48(3):669-73
references: 8452942
references: Endocrinology. 2006 Dec;147(12):5817-25
references: 16959837
references: Endocrinology. 2009 Nov;150(11):4874-82
references: 19819947
references: J Neurosci. 2009 Jul 22;29(29):9390-5
references: 19625529
references: Endocr Rev. 1992 Aug;13(3):387-414
references: 1425482
references: Nat Neurosci. 2004 Oct;7(10):1040-7
references: 15452575
references: Br J Sports Med. 2003 Dec;37(6):490-4
references: 14665585
references: Am J Clin Nutr. 2012 Aug;96(2):283-8
references: 22760567
references: Neuroendocrinology. 2003 Aug;78(2):90-5
references: 12915761
references: Endocrinol Metab Clin North Am. 2005 Sep;34(3):617-41, ix
references: 16085163
references: J Physiol. 2004 Dec 1;561(Pt 2):379-86
references: 15486019
references: Mol Cell Endocrinol. 2005 Oct 20;242(1-2):42-9
references: 16144737
references: Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2129-34
references: 15684075
references: Ann Med. 1994 Oct;26(5):331-40
references: 7826593
references: J Neurosci. 2005 Dec 7;25(49):11349-56
references: 16339030
references: Neuroendocrinology. 1993 Mar;57(3):525-31
references: 8321421
references: Biol Reprod. 1977 Sep;17(2):298-303
references: 889997
references: Cell Metab. 2007 Jun;5(6):438-49
references: 17550779
references: Endocrinology. 2006 Feb;147(2):816-26
references: 16293665
references: Eur J Endocrinol. 2012 Dec;167(6):733-47
references: 22989465
references: Trends Endocrinol Metab. 2009 Jul;20(5):237-42
references: 19541497
references: J Diabetes Complications. 2006 Jul-Aug;20(4):252-6
references: 16798477
references: Cell Metab. 2010 Apr 7;11(4):286-97
references: 20374961
references: Endocrinology. 2006 Mar;147(3):1154-8
references: 16373418
references: J Clin Invest. 2011 Jan;121(1):355-68
references: 21183787
references: Am J Physiol. 1990 Jul;259(1 Pt 2):R25-31
references: 2115745
references: J Comp Neurol. 2006 Jan 20;494(3):528-48
references: 16320257
references: Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10714-9
references: 17563351
references: Endocrinology. 2007 Oct;148(10):4927-36
references: 17595229
references: Science. 2000 Sep 22;289(5487):2122-5
references: 11000114
references: Neuroscience. 2011 Jan 26;173:37-56
references: 21093546
references: Nat Neurosci. 2011 Jun;14(6):704-10
references: 21516099
references: Trends Neurosci. 2007 Oct;30(10):504-11
references: 17904653
references: Cell Metab. 2008 Mar;7(3):236-48
references: 18316029
references: Endocrinology. 2010 Nov;151(11):5489-96
references: 20881239
references: Endocrinology. 2004 Oct;145(10):4565-74
references: 15242985
references: J Comp Neurol. 2008 Feb 20;506(6):895-911
references: 18085586
references: J Clin Endocrinol Metab. 2006 Aug;91(8):2888-91
references: 16684823
references: N Engl J Med. 2012 Feb 16;366(7):629-35
references: 22335740
references: Nature. 2001 May 31;411(6837):613-7
references: 11385580
references: Mol Cell Endocrinol. 2006 Jul 25;254-255:127-32
references: 16759792
references: Diabetes. 1990 Aug;39(8):942-8
references: 1973672
references: Endocr Rev. 2009 Oct;30(6):713-43
references: 19770291
references: Endocrinology. 2007 Oct;148(10):4601-11
references: 17595226
references: Biol Reprod. 1982 Sep;27(2):327-39
references: 6889895
references: Endocrinology. 2003 Oct;144(10):4484-91
references: 12960084
references: Endocrinology. 2009 Nov;150(11):5016-26
references: 19734277
references: J Reprod Fertil. 1969 Jul;19(2):215-22
references: 5815724