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, Gregory Dissen, Sergio Ojeda, L. Pinilla, Maneul Tena-Sempere

    Research output: Contribution to journalArticle

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    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

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    Puberty
    MicroRNAs
    Hypothalamus
    Delayed Puberty
    Species Specificity
    Sex Differentiation
    Organ Specificity
    RNA-Binding Proteins
    Genome-Wide Association Study
    Photoperiod
    Genomics
    Computational Biology
    Androgens
    Embryonic Development
    Haplorhini
    Estrogens
    Messenger RNA
    Brain

    ASJC Scopus subject areas

    • Endocrinology

    Cite this

    Sangiao-Alvarellos, S., Manfredi-Lozano, M., Ruiz-Pino, F., Navarro, V. M., Sánchez-Garrido, M. A., Leon, S., ... 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

    Changes in hypothalamic expression of the Lin28/let-7 system and related MicroRNAs during postnatal maturation and after experimental manipulations of puberty. / Sangiao-Alvarellos, Susana; Manfredi-Lozano, M.; Ruiz-Pino, F.; Navarro, V. M.; Sánchez-Garrido, M. A.; Leon, S.; Dieguez, C.; Cordido, F.; Matagne, V.; Dissen, Gregory; Ojeda, Sergio; Pinilla, L.; Tena-Sempere, Maneul.

    In: Endocrinology, Vol. 154, No. 2, 01.02.2013, p. 942-955.

    Research output: Contribution to journalArticle

    Sangiao-Alvarellos, S, Manfredi-Lozano, M, Ruiz-Pino, F, Navarro, VM, Sánchez-Garrido, MA, Leon, S, Dieguez, C, Cordido, F, Matagne, V, Dissen, G, Ojeda, S, 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, vol. 154, no. 2, pp. 942-955. https://doi.org/10.1210/en.2012-2006
    Sangiao-Alvarellos, Susana ; Manfredi-Lozano, M. ; Ruiz-Pino, F. ; Navarro, V. M. ; Sánchez-Garrido, M. A. ; Leon, S. ; Dieguez, C. ; Cordido, F. ; Matagne, V. ; Dissen, Gregory ; Ojeda, Sergio ; Pinilla, L. ; Tena-Sempere, Maneul. / Changes in hypothalamic expression of the Lin28/let-7 system and related MicroRNAs during postnatal maturation and after experimental manipulations of puberty. In: Endocrinology. 2013 ; Vol. 154, No. 2. pp. 942-955.
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    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.",
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    AU - Ruiz-Pino, F.

    AU - Navarro, V. M.

    AU - Sánchez-Garrido, M. A.

    AU - Leon, S.

    AU - Dieguez, C.

    AU - Cordido, F.

    AU - Matagne, V.

    AU - Dissen, Gregory

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