ESPE Abstracts (2014) 82 S6.1

Roles of Hypothalamic microRNAs in the Regulation of Puberty

Manuel Tena-Semperea,b,c

aDepartment of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain; bCIBER Fisiopatología de la Obesidad y Nutrición, Córdoba, Spain; cInstituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004 Córdoba, Spain

Puberty, as the developmental continuum between infancy and adulthood, is a complex maturational transition, affecting different body systems, which is under the control of sophisticated regulatory networks. Concerning the pubertal awakening of the reproductive axis, much has been learnt in the last decades on the central mechanisms whereby puberty onset is driven. However, most of the information so far available is limited to the roles of specific neurotransmitters and their receptors, as well as the transcriptional mechanisms responsible for their regulation. The sophisticated nature of puberty, though, makes it reasonable to predict that its precise regulation involves not only the classical control of gene transcription, but also the participation of additional regulatory events, such as epigenetics, defined as the mechanisms for genetic control other than the information encoded by the mere DNA sequence. Such epigenetic mechanisms include not only DNA methylation and histone modifications, but also the regulatory actions of small, non-coding (nc) RNAs, mainly microRNAs. MiRNAs are small (~22 nt), nc RNAs that operate as post-transcriptional regulators by virtue of their ability to bind seed sequences at the 3′-UTR of different target RNAs, thus resulting (in most cases) in gene silencing. While the role of other epigenetic phenomena (e.g. methylation of specific repressors) in the central control of puberty has been recently documented, the involvement of putative miRNA pathways in the modulation of central (or peripheral) elements of the reproductive axis remains scarcely evaluated. Yet, human and functional genomic data have recently suggested the participation of the RNA-binding protein, Lin28B, in the control of puberty; the major known role of Lin28B being to inhibit the maturation of the members of the miRNA family, let-7. Departing from these observations, in this presentation we will review our, as yet limited, knowledge on the roles of miRNAs in the central control of reproduction and gonadal function. Special attention will be paid to summarize data from expression analyses and recent functional genomic studies addressing the pubertal impact of conditional elimination of miRNA synthesis in key neuronal populations of the reproductive brain. In doing so, we intend to provide an updated (and broader) view of the actual mechanisms whereby maturation of the reproductive axis is finely controlled (and eventually deregulated) during puberty onset.

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