NELL2 participates in formation of the sexually dimorphic nucleus of the pre-optic area in rats

Jin Kwon Jeong, Byung Jun Ryu, Jungil Choi, Dong Hee Kim, Eun Jung Choi, Jeong Woo Park, Joong Jean Park, Byung Ju Lee

    Research output: Contribution to journalArticlepeer-review

    16 Citations (Scopus)

    Abstract

    Formation of the sexually dimorphic nucleus of the pre-optic area (SDN-POA) in the rat hypothalamus shows a sexually differential development of neurons. Volume of the SDN-POA in males is much bigger than that in females which is because of a neuroprotective effect of estradiol converted from circulating testosterone during a critical period of brain development. We found that neural epidermal growth factor-like like-2 (NELL2), a neural tissue-enriched protein, is a potential downstream target of estrogen. In this study, we examined a possible role of NELL2 in the development of the SDN-POA and in the normalcy of sexual behavior in the male rats. NELL2 was expressed and co-localized with estrogen receptor alpha in the SDN-POA. A blockade of NELL2 synthesis in the brain during postnatal day 0 (d0) to d4 by an intracerebroventricular injection of an antisense NELL2 oligodeoxynucleotide, resulted in a decrease in volume of the SDN-POA in males. Interestingly, it reduced some components of the male sexual behavior such as mounting and intromission, but not the sexual partner preference in adulthood. In vitro study using the hippocampal neuroprecursor HiB5 cells showed that NELL2 has a protective effect from a cell death condition. These data suggest that a relevant expression of NELL2 in the neonatal brain is important for the estrogen-induced normal development of the SDN-POA and the normalcy of sexual behavior in male rats.

    Original languageEnglish
    Pages (from-to)1604-1613
    Number of pages10
    JournalJournal of Neurochemistry
    Volume106
    Issue number4
    DOIs
    Publication statusPublished - 2008 Aug

    Keywords

    • Estrogen-dependent neuroprotection
    • Sexual behavior
    • Sexual development
    • Sexually dimorphic nucleus pre-optic area

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

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