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Gonadotropin-Inhibitory Hormone Neurons Interact Directly with Gonadotropin-Releasing Hormone-I and -II Neurons in European Starling Brain

Laboratory of Reproductive Neuroendocrinology (T.U., S.K., Y.-c.H., J.R., J.J., G.E.B.), Department of Integrative Biology and Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, California 94720-3140; and Laboratory of Integrative Brain Sciences (T.O., V.S.C., K.T.), Department of Biology, Waseda University, Shinjuku-ku, Tokyo 169-8050, Japan

Address all correspondence and requests for reprints to: Takayoshi Ubuka, Ph.D., Laboratory of Reproductive Neuroendocrinology, Department of Integrative Biology, University of California at Berkeley, 3060 Valley Life Sciences Building No. 3140, Berkeley, California 94720-3140. E-mail: ubukat{at}berkeley.edu.

Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic dodecapeptide (SIKPSAYLPLRF-NH₂) that directly inhibits gonadotropin synthesis and release from quail pituitary. The action of GnIH is mediated by a novel G-protein coupled receptor. This gonadotropin-inhibitory system may be widespread in vertebrates, at least birds and mammals. In these higher vertebrates, histological evidence suggests contact of GnIH immunoreactive axon terminals with GnRH neurons, thus indicating direct regulation of GnRH neuronal activity by GnIH. In this study we investigated the interaction of GnIH and GnRH-I and -II neurons in European starling (Sturnus vulgaris) brain. Cloned starling GnIH precursor cDNA encoded three peptides that possess characteristic LPXRF-amide (X = L or Q) motifs at the C termini. Starling GnIH was further identified as SIKPFANLPLRF-NH₂ by mass spectrometry combined with immunoaffinity purification. GnIH neurons, identified by in situ hybridization and immunocytochemistry (ICC), were clustered in the hypothalamic paraventricular nucleus. GnIH immunoreactive fiber terminals were present in the external layer of the median eminence in addition to the preoptic area and midbrain, where GnRH-I and GnRH-II neuronal cell bodies exist, respectively. GnIH axon terminals on GnRH-I and -II neurons were shown by GnIH and GnRH double-label ICC. Furthermore, the expression of starling GnIH receptor mRNA was identified in both GnRH-I and GnRH-II neurons by in situ hybridization combined with GnRH ICC. The cellular localization of GnIH receptor has not previously been identified in any vertebrate brain. Thus, GnIH may regulate reproduction of vertebrates by directly modulating GnRH-I and GnRH-II neuronal activity, in addition to influencing the pituitary gland.

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				I. J. Clarke, I. P. Sari, Y. Qi, J. T. Smith, H. C. Parkington, T. Ubuka, J. Iqbal, Q. Li, A. Tilbrook, K. Morgan, et al. Potent Action of RFamide-Related Peptide-3 on Pituitary Gonadotropes Indicative of a Hypophysiotropic Role in the Negative Regulation of Gonadotropin Secretion Endocrinology, November 1, 2008; 149(11): 5811 - 5821. [Abstract] [Full Text] [PDF]

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