title: Changes in hypothalamic expression of the Lin28/let-7 system and related microRNAs during postnatal maturation and after experimental manipulations of puberty.
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.
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Avda, Menendez Pidal s/n.14004, University of Córdoba, Córdoba, Spain. susana.sangiao@udc.es
authors.forename: S
authors.initials: S
authors.lastname: Sangiao-Alvarellos
authors.forename: M
authors.initials: M
authors.lastname: Manfredi-Lozano
authors.forename: F
authors.initials: F
authors.lastname: Ruiz-Pino
authors.forename: V M
authors.initials: VM
authors.lastname: Navarro
authors.forename: M A
authors.initials: MA
authors.lastname: Sánchez-Garrido
authors.forename: S
authors.initials: S
authors.lastname: Leon
authors.forename: C
authors.initials: C
authors.lastname: Dieguez
authors.forename: F
authors.initials: F
authors.lastname: Cordido
authors.forename: V
authors.initials: V
authors.lastname: Matagne
authors.forename: G A
authors.initials: GA
authors.lastname: Dissen
authors.forename: S R
authors.initials: SR
authors.lastname: Ojeda
authors.forename: L
authors.initials: L
authors.lastname: Pinilla
authors.forename: M
authors.initials: M
authors.lastname: Tena-Sempere
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000254:growth & development*; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D007031:Hypothalamus / Q000254:growth & development / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D011627:Puberty / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: C548821:MIRN132 microRNA, rat; C542511:MIRN145 microRNA, rat; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins