Neuroendocrinology

GnRH, Gonadotropins, Gonadal Steroids and Reproduction

NELL2, a Neuron-Specific EGF-Like Protein, Is Selectively Expressed in Glutamatergic Neurons and Contributes to the Glutamatergic Control of GnRH Neurons at Puberty

Ha C.M.a · Choi J.a · Choi E.J.a · Costa M.E.b · Lee B.J.a · Ojeda S.R.b

Author affiliations

aDepartment of Biological Sciences, University of Ulsan, Ulsan, South Korea; bDivision of Neuroscience, Oregon National Primate Research Center/Oregon Health and Science University, Beaverton, Oreg., USA

Keywords: Epidermal growth factor-like repeat domainsCa2+-binding proteinSynaptophysinGlutamate releaseFemale puberty

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Neuroendocrinology 2008;88:199–211
https://doi.org/10.1159/000139579

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Article / Publication Details

First-Page Preview
Abstract of GnRH, Gonadotropins, Gonadal Steroids and Reproduction

Received: January 03, 2008
Accepted: February 08, 2008
Published online: June 12, 2008
Issue release date: October 2008

Number of Print Pages: 13
Number of Figures: 6
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

Abstract

NELL2, a protein containing EGF-like repeats, is almost exclusively expressed in the nervous system. In the mammalian brain, NELL2 expression is mostly neuronal. NELL2 was previously found to be a secreted protein that functions during embryonic development as a neuronal differentiation and survival factor. We now show that the Nell2 gene is selectively expressed in the two major subtypes of glutamatergic neurons described in the postnatal brain: those containing the vesicular glutamate transporter 1 and those expressing vesicular glutamate transporter 2. No Nell2 mRNA is detected in GABAergic neurons. Likewise, GnRH neurons are devoid of NELL2. During prepubertal development of the female rat, Nell2 mRNA abundance increases selectively in the medial basal hypothalamus, reaching maximal values at the end of the juvenile period, to decline at the time of puberty to intermediate levels. Similar, but less pronounced changes are observed in the preoptic area, but they are absent in the cerebral cortex. A well-established glutamatergic function in the neuroendocrine brain is to enhance release of GnRH, the neurohormone controlling sexual development and the time of puberty. In vivo disruption of NELL2 synthesis via intraventricular administration of antisense oligodeoxynucleotides reduced GnRH release from the medial basal hypothalamus and delayed the initiation of female puberty. These results identify NELL2 as a new component of glutamatergic neurons and provide evidence for its physiological involvement in a major, glutamate-dependent, process of neuroendocrine regulation.

© 2008 S. Karger AG, Basel



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Article / Publication Details

First-Page Preview
Abstract of GnRH, Gonadotropins, Gonadal Steroids and Reproduction

Received: January 03, 2008
Accepted: February 08, 2008
Published online: June 12, 2008
Issue release date: October 2008

Number of Print Pages: 13
Number of Figures: 6
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

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2008, Vol.88, No. 3

October 2008

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B.J. Lee and S.R. Ojeda are equal correspondents for this work.
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