The Oct-2 POU domain gene in the neuroendocrine brain

A transcriptional regulator of mammalian puberty

Sergio Ojeda, Jennifer Hill, Diane F. Hill, Maria E. Costa, Veronica Tapia, Anda Cornea, Ying J. Ma

    Research output: Contribution to journalArticle

    69 Citations (Scopus)

    Abstract

    POU homeodomain genes are transcriptional regulators that control development of the mammalian forebrain. Although they are mostly active during embryonic life, some of them remain expressed in the postnatal hypothalamus, suggesting their involvement in regulating differentiated functions of the neuroendocrine brain. We show here that Oct-2, a POU domain gene originally described in cells of the immune system, is one of the controlling components of the cell-cell signaling process underlying the hypothalamic regulation of female puberty. Lesions of the anterior hypothalamus cause sexual precocity and recapitulate some of the events leading to the normal initiation of puberty. Prominent among these events is an increased astrocytic expression of the gene encoding transforming growth factor-α (TGFα), a tropic polypeptide involved in the stimulatory control of LHRH secretion. The present study shows that such lesions result in the rapid and selective increase in Oct-2 transcripts in TGFα-containing astrocytes surrounding the lesion site. In both lesion-induced and normal puberty, there is a preferential increase in hypothalamic expression of the Oct-2a and Oct-2c alternatively spliced messenger RNA forms of the Oct-2 gene, with an increase in 2a messenger RNA levels preceding that in 2c and antedating the peripubertal activation of gonadal steroid secretion. Both Oct-2a and 2c transactivate the TGFα gene via recognition motifs contained in the TGFα gene promoter. Inhibition of Oct-2 synthesis reduces TGFα expression in astroglial cells and delays the initiation of puberty. These results suggest that the Oct-2 gene is one of the upstream components of the glia to neuron signaling process that controls the onset of female puberty in mammals.

    Original languageEnglish (US)
    Pages (from-to)3774-3789
    Number of pages16
    JournalEndocrinology
    Volume140
    Issue number8
    StatePublished - 1999

    Fingerprint

    Transforming Growth Factors
    Puberty
    Brain
    Genes
    Anterior Hypothalamus
    Messenger RNA
    Cellular Structures
    Regulator Genes
    Prosencephalon
    Gonadotropin-Releasing Hormone
    Neuroglia
    Astrocytes
    Hypothalamus
    Mammals
    Immune System
    Steroids
    Gene Expression
    Neurons
    Peptides

    ASJC Scopus subject areas

    • Endocrinology
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Ojeda, S., Hill, J., Hill, D. F., Costa, M. E., Tapia, V., Cornea, A., & Ma, Y. J. (1999). The Oct-2 POU domain gene in the neuroendocrine brain: A transcriptional regulator of mammalian puberty. Endocrinology, 140(8), 3774-3789.

    The Oct-2 POU domain gene in the neuroendocrine brain : A transcriptional regulator of mammalian puberty. / Ojeda, Sergio; Hill, Jennifer; Hill, Diane F.; Costa, Maria E.; Tapia, Veronica; Cornea, Anda; Ma, Ying J.

    In: Endocrinology, Vol. 140, No. 8, 1999, p. 3774-3789.

    Research output: Contribution to journalArticle

    Ojeda, S, Hill, J, Hill, DF, Costa, ME, Tapia, V, Cornea, A & Ma, YJ 1999, 'The Oct-2 POU domain gene in the neuroendocrine brain: A transcriptional regulator of mammalian puberty', Endocrinology, vol. 140, no. 8, pp. 3774-3789.
    Ojeda, Sergio ; Hill, Jennifer ; Hill, Diane F. ; Costa, Maria E. ; Tapia, Veronica ; Cornea, Anda ; Ma, Ying J. / The Oct-2 POU domain gene in the neuroendocrine brain : A transcriptional regulator of mammalian puberty. In: Endocrinology. 1999 ; Vol. 140, No. 8. pp. 3774-3789.
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