Changes in hypothalamic expression of the Lin28/let-7 system and related MicroRNAs during postnatal maturation and after experimental manipulations of puberty

Susana Sangiao-Alvarellos, M. Manfredi-Lozano, F. Ruiz-Pino, V. M. Navarro, M. A. Sánchez-Garrido, S. Leon, C. Dieguez, F. Cordido, V. Matagne, G. A. Dissen, S. R. Ojeda, L. Pinilla, Maneul Tena-Sempere

    Research output: Contribution to journalArticle

    70 Scopus citations

    Abstract

    Lin28 and Lin28b are related RNA-binding proteins that inhibit the maturation of miRNAs of the let-7 family and participate in the control of cellular stemness and early embryonic development. Considerable interest has arisen recently concerning other physiological roles of the Lin28/let-7 axis, including its potential involvement in the control of puberty, as suggested by genome-wide association studies and functional genomics. We report herein the expression profiles of Lin28 and let-7 members in the rat hypothalamus during postnatal maturation and in selected models of altered puberty. The expression patterns of c-Myc (upstream positive regulator of Lin28), mir-145 (negative regulator of c-Myc), and mir-132 and mir-9 (putative miRNA repressors of Lin28, predicted by bioinformatic algorithms) were also explored. In male and female rats, Lin28, Lin28b, and c-Myc mRNAs displayed very high hypothalamic expression during the neonatal period, markedly decreased during the infantile-to-juvenile transition and reached minimal levels before/around puberty. A similar puberty-related decline was observed for Lin28b in monkey hypothalamus but not in the rat cortex, suggesting species conservation and tissue specificity. Conversely, let-7a, let-7b, mir-132, and mir-145, but not mir-9, showed opposite expression profiles. Perturbation of brain sex differentiation and puberty, by neonatal treatment with estrogen or androgen, altered the expression ratios of Lin28/let-7 at the time of puberty. Changes in the c-Myc/Lin28b/let-7 pathway were also detected in models of delayed puberty linked to early photoperiod manipulation and, to a lesser extent, postnatal underfeeding or chronic subnutrition. Altogether, our data are the first to document dramatic changes in the expression of the Lin28/let-7 axis in the rat hypothalamus during the postnatal maturation and after different manipulations that disturb puberty, thus suggesting the potential involvement of developmental changes in hypothalamic Lin28/let-7 expression in the mechanisms permitting/leading to puberty onset.

    Original languageEnglish (US)
    Pages (from-to)942-955
    Number of pages14
    JournalEndocrinology
    Volume154
    Issue number2
    DOIs
    StatePublished - Feb 1 2013

    ASJC Scopus subject areas

    • Endocrinology

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  • Cite this

    Sangiao-Alvarellos, S., Manfredi-Lozano, M., Ruiz-Pino, F., Navarro, V. M., Sánchez-Garrido, M. A., Leon, S., Dieguez, C., Cordido, F., Matagne, V., Dissen, G. A., Ojeda, S. R., Pinilla, L., & Tena-Sempere, M. (2013). Changes in hypothalamic expression of the Lin28/let-7 system and related MicroRNAs during postnatal maturation and after experimental manipulations of puberty. Endocrinology, 154(2), 942-955. https://doi.org/10.1210/en.2012-2006