期刊
ENDOCRINOLOGY
卷 154, 期 2, 页码 942-955出版社
OXFORD UNIV PRESS INC
DOI: 10.1210/en.2012-2006
关键词
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资金
- Ministerio de Economia y Competitividad, Spain [BFU 2008-00984, BFU 2011-25021]
- FEDER Program from European Union [EU]
- Junta de Andalucia, Spain [P08-CVI-03788]
- U.S. National Institutes of Health [HD025123-ARRA]
- U.S. National Science Foundation [IOS1121691]
- Instituto de Salud Carlos III [PI10/00088 FIS]
- FEDER Program from EU
- Xunta de Galicia, Spain [IN845B-2010/187, 10CSA916014PR]
- Xunta de Galicia [IN809A: 08.02.561B.480.0, 08.02.561A.480.1]
- [P51-OD 011092-53]
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [1121691] Funding Source: National Science Foundation
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. (Endocrinology 154: 942-955, 2013)
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