An alternative transcription start site yields estrogen-unresponsive kiss1 mRNA transcripts in the hypothalamus of prepubertal female rats

Juan Manuel Castellano, Hollis Wright, Sergio R. Ojeda, Alejandro Lomniczi

    Research output: Contribution to journalArticle

    6 Scopus citations

    Abstract

    The importance of the Kiss1 gene in the control of reproductive development is well documented. However, much less is known about the transcriptional regulation of Kiss1 expression in the hypothalamus. Critical for these studies is an accurate identification of the site(s) where Kiss1 transcription is initiated. Employing 5′-RACE PCR, we detected a transcription start site (TSS1) used by the hypothalamus of rats, mice, nonhuman primates and humans to initiate Kiss1 transcription. In rodents, an exon 1 encoding 5′-untranslated sequences is followed by an alternatively spliced second exon, which encodes 5′-untranslated regions of two different lengths and contains the translation initiation codon (ATG). In nonhuman primates and humans, exon 2 is not alternatively spliced. Surprisingly, in rat mediobasal hypothalamus (MBH), but not preoptic area (POA), an additional TSS (TSS2) located upstream from TSS1 generates an exon 1 longer (377 bp) than the TSS1-derived exon 1 (98 bp). The content of TSS1-derived transcripts increased at puberty in the POA and MBH of female rats. It also increased in the MBH after ovariectomy, and this change was prevented by estrogen. In contrast, no such changes in TSS2-derived transcript abundance were detected. Promoter assays showed that the proximal TSS1 promoter is much more active than the putative TSS2 promoter, and that only the TSS1 promoter is regulated by estrogen. These differences appear to be related to the presence of a TATA box and binding sites for transcription factors activating transcription and interacting with estrogen receptor-α in the TSS1, but not TSS2, promoter.

    Original languageEnglish (US)
    Pages (from-to)94-107
    Number of pages14
    JournalNeuroendocrinology
    Volume99
    Issue number2
    DOIs
    StatePublished - Jul 2014

    Keywords

    • Hypothalamus
    • Kiss1 gene
    • Puberty
    • Rats
    • Transcriptional start site

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Endocrinology
    • Endocrine and Autonomic Systems
    • Cellular and Molecular Neuroscience

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