title: dynorphin-kappa opioid receptor signaling partly mediates estrogen negative feedback effect on LH pulses in female rats.
abstract: Accumulating evidence suggests that the arcuate nucleus (ARC) kisspeptin/neurokinin B (NKB)/dynorphin (KNDy) neurons play a role in estrogen negative feedback action on pulsatile gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release. The present study aimed to determine if dynorphin (Dyn) is involved in estrogen negative feedback on pulsatile GnRH/LH release. The effect of the injection of nor-binaltorphimine (nor-BNI), a kappa-opioid receptor (KOR) antagonist, into the third cerebroventricle (3V) on LH pulses was determined in ovariectomized (OVX) adult female rats with/without replacement of negative feedback levels of estradiol (low E2). The mean LH concentrations and baseline levels of LH secretion in nor-BNI-injected, low E2-treated rats were significantly higher compared with vehicle-treated controls. On the other hand, the nor-BNI treatment failed to affect any LH pulse parameters in OVX rats without low E2 treatment. These results suggest that Dyn is involved in the estrogen negative feedback regulation of pulsatile GnRH/LH release. The low E2 treatment had no significant effect on the numbers of ARC Pdyn (Dyn gene)-,Kiss1- and Tac2 (NKB gene)-expressing cells. The treatment also did not affect mRNA levels of Pdyn and Oprk1 (KOR gene) in the ARC-median eminence region, but significantly increased the ARC kisspeptin immunoreactivity. These findings suggest that the negative feedback level of estrogen suppresses kisspeptin release from the ARC KNDy neurons through an unknown mechanism without affecting the Dyn and KOR expressions in the ARC. Taken together, the present result suggests that Dyn-KOR signaling is a part of estrogen negative feedback action on GnRH/LH pulses by reducing the kisspeptin release in female rats.
authors: Laboratory of Reproductive Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors: Parvin
authors: P
authors: Mostari
authors: Nahoko
authors: N
authors: Ieda
authors: Chikaya
authors: C
authors: Deura
authors: Shiori
authors: S
authors: Minabe
authors: Shunji
authors: S
authors: Yamada
authors: Yoshihisa
authors: Y
authors: Uenoyama
authors: Kei-ichiro
authors: K
authors: Maeda
authors: Hiroko
authors: H
authors: Tsukamura
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D002552:Cerebral Ventricles / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D025461:Feedback, Physiological; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D059648:Kisspeptins / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism*; D015287:Neurokinin B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010052:Ovariectomy; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D015398:Signal Transduction; D015320:Tachykinins / Q000378:metabolism
chemical_list: D004967:Estrogens; C491406:Kiss1 protein, rat; D059648:Kisspeptins; D011498:Protein Precursors; D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; D015320:Tachykinins; C044206:preprotachykinin; D004399:Dynorphins; D015287:Neurokinin B; D007986:Luteinizing Hormone
references: Endocrinology. 1992 Oct;131(4):1650-6
references: 1327717
references: J Mol Endocrinol. 2008 Nov;41(5):263-75
references: 18772268
references: Biol Reprod. 1988 Dec;39(5):1032-8
references: 3219376
references: J Physiol. 1987 Dec;394:23-39
references: 2895179
references: Neuroendocrinology. 1984 Dec;39(6):517-23
references: 6514136
references: Endocrinology. 2005 Sep;146(9):3686-92
references: 15919741
references: Mol Cell Endocrinol. 2008 Aug 13;290(1-2):24-30
references: 18534740
references: Am J Physiol. 1982 Oct;243(4):E310-8
references: 6889816
references: Endocr Rev. 2009 Oct;30(6):713-43
references: 19770291
references: Endocrinology. 2005 Oct;146(10):4431-6
references: 15976058
references: J Neuroendocrinol. 2009 Oct;21(10):813-21
references: 19678868
references: Proc Natl Acad Sci U S A. 2007 May 8;104(19):8173-7
references: 17470805
references: Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E202-10
references: 21045176
references: J Neuroendocrinol. 2009 Jun;21(6):527-37
references: 19500223
references: Endocrinology. 2010 Sep;151(9):4494-503
references: 20573725
references: J Neurosci. 2009 Sep 23;29(38):11859-66
references: 19776272
references: Neuroendocrinology. 1991 Oct;54(4):321-6
references: 1758574
references: Brain Res. 2010 Dec 10;1364:103-15
references: 20951683
references: Biol Reprod. 2009 Dec;81(6):1216-25
references: 19684332
references: Pharm Res. 1984 Jan;1(1):46-8
references: 24277186
references: Endocr Rev. 1998 Jun;19(3):302-30
references: 9626556
references: J Comp Neurol. 2001 Apr 30;433(2):222-38
references: 11283961
references: Endocrinology. 2010 Aug;151(8):3479-89
references: 20501670
references: Endocrinology. 2012 Oct;153(10):4894-904
references: 22903614
references: Proc Natl Acad Sci U S A. 1980 Oct;77(10):6207-10
references: 6108564
references: Endocrinology. 1980 Aug;107(2):498-503
references: 7190094
references: Endocrinology. 2008 Mar;149(3):1004-8
references: 18063679
references: J Neurosci. 2010 Feb 24;30(8):3124-32
references: 20181609
references: J Endocrinol. 1989 May;121(2):277-83
references: 2754361
references: J Reprod Dev. 2007 Apr;53(2):367-78
references: 17213691
references: J Med Chem. 1987 Feb;30(2):238-9
references: 3027336
references: Brain Res. 2010 Dec 10;1364:116-28
references: 20800582
references: J Neuroendocrinol. 1990 Oct 1;2(5):685-91
references: 19215406
references: J Endocrinol. 1991 Jun;129(3):321-8
references: 2066689
references: Endocrinology. 2011 Sep;152(9):3451-60
references: 21693677
references: Peptides. 2009 Jan;30(1):49-56
references: 18775461
references: J Comp Neurol. 1986 Jul 15;249(3):293-336
references: 2874159
references: Endocrinology. 2004 Jun;145(6):2959-67
references: 14988383
references: Neuroendocrinology. 1984 Sep;39(3):256-60
references: 6504270
references: Rev Endocr Metab Disord. 2007 Mar;8(1):21-9
references: 17377846
references: Endocrinology. 1994 Apr;134(4):1806-11
references: 8137746
references: Endocrinology. 2012 Jun;153(6):2800-12
references: 22508514
references: Annu Rev Physiol. 1987;49:365-82
references: 3551806
references: Mol Endocrinol. 2009 Mar;23(3):349-59
references: 19131510
references: Biol Reprod. 1992 Feb;46(2):163-7
references: 1536890
references: Endocrinology. 1965 Sep;77(3):553-62
references: 4284469
references: Life Sci. 1989;44(10):661-5
references: 2538689
references: PLoS One. 2012;7(9):e44344
references: 23028524
references: Endocrinology. 2007 Dec;148(12):5752-60
references: 17823266