title: KNDy Neurons Modulate the Magnitude of the Steroid-Induced Luteinizing Hormone Surges in Ovariectomized Rats.
abstract: Kisspeptin is the most potent stimulator of LH release. There are two kisspeptin neuronal populations in the rodent brain: in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus. The arcuate neurons coexpress kisspeptin, neurokinin B, and dynorphin and are called KNDy neurons. Because estradiol increases kisspeptin expression in the AVPV whereas it inhibits KNDy neurons, AVPV and KNDy neurons have been postulated to mediate the positive and negative feedback effects of estradiol on LH secretion, respectively. Yet the role of KNDy neurons during the positive feedback is not clear. In this study, ovariectomized rats were microinjected bilaterally into the arcuate nucleus with a saporin-conjugated neurokinin B receptor agonist for targeted ablation of approximately 70% of KNDy neurons. In oil-treated animals, ablation of KNDy neurons impaired the rise in LH after ovariectomy and kisspeptin content in both populations. In estradiol-treated animals, KNDy ablation did not influence the negative feedback of steroids during the morning. Surprisingly, KNDy ablation increased the steroid-induced LH surges, accompanied by an increase of kisspeptin content in the AVPV. This increase seems to be due to lack of dynorphin input from KNDy neurons to the AVPV as the following: 1) microinjections of a dynorphin antagonist into the AVPV significantly increased the LH surge in estradiol-treated rats, similar to KNDy ablation, and 2) intra-AVPV microinjections of dynorphin in KNDy-ablated rats restored LH surge levels. Our results suggest that KNDy neurons provide inhibition to AVPV kisspeptin neurons through dynorphin and thus regulate the amplitude of the steroid-induced LH surges.
authors: Program in Neuroscience and Department of Mathematics (C.V.H., R.B.) and Program in Neuroscience and Department of Biology (A.M.S.), Florida State University, Tallahassee, Florida 32306; Department of Biology (N.T., V.V.P.), Washington and Lee University, Lexington, Virginia 24450; and Department of Physiology (B.K.), Medical School, and Department of Morphology, Stomatology, and Physiology (R.O.C., J.A.A.-F.), School of Dentistry, University of São Paulo, Ribeirão Preto 14040-900, SP, Brazil.
authors: Cleyde V
authors: CV
authors: Helena
authors: Program in Neuroscience and Department of Mathematics (C.V.H., R.B.) and Program in Neuroscience and Department of Biology (A.M.S.), Florida State University, Tallahassee, Florida 32306; Department of Biology (N.T., V.V.P.), Washington and Lee University, Lexington, Virginia 24450; and Department of Physiology (B.K.), Medical School, and Department of Morphology, Stomatology, and Physiology (R.O.C., J.A.A.-F.), School of Dentistry, University of São Paulo, Ribeirão Preto 14040-900, SP, Brazil.
authors: Natalia
authors: N
authors: Toporikova
authors: Program in Neuroscience and Department of Mathematics (C.V.H., R.B.) and Program in Neuroscience and Department of Biology (A.M.S.), Florida State University, Tallahassee, Florida 32306; Department of Biology (N.T., V.V.P.), Washington and Lee University, Lexington, Virginia 24450; and Department of Physiology (B.K.), Medical School, and Department of Morphology, Stomatology, and Physiology (R.O.C., J.A.A.-F.), School of Dentistry, University of São Paulo, Ribeirão Preto 14040-900, SP, Brazil.
authors: Bruna
authors: B
authors: Kalil
authors: Program in Neuroscience and Department of Mathematics (C.V.H., R.B.) and Program in Neuroscience and Department of Biology (A.M.S.), Florida State University, Tallahassee, Florida 32306; Department of Biology (N.T., V.V.P.), Washington and Lee University, Lexington, Virginia 24450; and Department of Physiology (B.K.), Medical School, and Department of Morphology, Stomatology, and Physiology (R.O.C., J.A.A.-F.), School of Dentistry, University of São Paulo, Ribeirão Preto 14040-900, SP, Brazil.
authors: Andrea M
authors: AM
authors: Stathopoulos
authors: Program in Neuroscience and Department of Mathematics (C.V.H., R.B.) and Program in Neuroscience and Department of Biology (A.M.S.), Florida State University, Tallahassee, Florida 32306; Department of Biology (N.T., V.V.P.), Washington and Lee University, Lexington, Virginia 24450; and Department of Physiology (B.K.), Medical School, and Department of Morphology, Stomatology, and Physiology (R.O.C., J.A.A.-F.), School of Dentistry, University of São Paulo, Ribeirão Preto 14040-900, SP, Brazil.
authors: Veronika V
authors: VV
authors: Pogrebna
authors: Program in Neuroscience and Department of Mathematics (C.V.H., R.B.) and Program in Neuroscience and Department of Biology (A.M.S.), Florida State University, Tallahassee, Florida 32306; Department of Biology (N.T., V.V.P.), Washington and Lee University, Lexington, Virginia 24450; and Department of Physiology (B.K.), Medical School, and Department of Morphology, Stomatology, and Physiology (R.O.C., J.A.A.-F.), School of Dentistry, University of São Paulo, Ribeirão Preto 14040-900, SP, Brazil.
authors: Ruither O
authors: RO
authors: Carolino
authors: Program in Neuroscience and Department of Mathematics (C.V.H., R.B.) and Program in Neuroscience and Department of Biology (A.M.S.), Florida State University, Tallahassee, Florida 32306; Department of Biology (N.T., V.V.P.), Washington and Lee University, Lexington, Virginia 24450; and Department of Physiology (B.K.), Medical School, and Department of Morphology, Stomatology, and Physiology (R.O.C., J.A.A.-F.), School of Dentistry, University of São Paulo, Ribeirão Preto 14040-900, SP, Brazil.
authors: Janete A
authors: JA
authors: Anselmo-Franci
authors: Program in Neuroscience and Department of Mathematics (C.V.H., R.B.) and Program in Neuroscience and Department of Biology (A.M.S.), Florida State University, Tallahassee, Florida 32306; Department of Biology (N.T., V.V.P.), Washington and Lee University, Lexington, Virginia 24450; and Department of Physiology (B.K.), Medical School, and Department of Morphology, Stomatology, and Physiology (R.O.C., J.A.A.-F.), School of Dentistry, University of São Paulo, Ribeirão Preto 14040-900, SP, Brazil.
authors: Richard
authors: R
authors: Bertram
mesh_terms: D000818:Animals; D004399:Dynorphins / Q000378:metabolism*; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D059648:Kisspeptins / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood*; D015287:Neurokinin B / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010052:Ovariectomy; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D059648:Kisspeptins; D004399:Dynorphins; D015287:Neurokinin B; D007986:Luteinizing Hormone