Investigation of peripubertal expression of Lin28a and Lin28b in C57BL/6 female mice

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:365

Article

Grieco, Anthony^1,2  Rzeczkowska, Paulina^1,2  Alm, Christina¹  Palmert, Mark R.^1,2,3,4 

[1] Univ Toronto, Hosp Sick Children, Div Endocrinol, Toronto, ON M5G 1X8, Canada

[2] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada

[3] Univ Toronto, Dept Paediat, Toronto, ON M5S 1A8, Canada

[4] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada

关键词: Puberty;    Lin28a;    Lin28b;    Hypothalamic-pituitary-gonadal axis;   

DOI  :  10.1016/j.mce.2012.10.025

来源: Elsevier

【 摘 要 】

Genome-wide association studies recently identified 32 loci that associate with the age at menarche (AAM) in humans. Because the locus most robustly associated with AAM is in/near LIN28B, the goal of this study was to investigate how the Lin28 pathway might modulate pubertal timing by examining expression of Lin28b, and its homologue, Lin28a, across the pubertal transition in female mice. Quantitative reverse-transcriptase PCR data indicate that, prior to the onset of puberty, expression of both Lin28b and Lin28a decreases in the ovary, while expression of only Lin28a decreases in the hypothalamus; the expression of Lin28a increases after the onset of puberty in the pituitary. Immunohistochemistry in ovarian tissue verified that Lin28a protein levels decreased in parallel with gene expression. Although these data do not demonstrate cause and effect, they do suggest that decreased expression of Lin28a/Lin28b may facilitate the transition into puberty, consistent with previous data showing that overexpression of Lin28a in transgenic mice leads to delayed puberty. In addition, although Lin28b and/or Lin28a expression significantly decreased prior to puberty, neither Let-7a nor Let-7g miRNA levels changed significantly, raising the possibility that some effects of L1n28b and Lin28a within the hypothalamic-pituitary-gonadal (HPG) axis may be Let-7 miRNA independent. Subsequent studies, such as tissue and age specific modulation of Lin28b and Lin28a expression, could determine whether the expression patterns observed are responsible for modulating the onset of puberty and delineate further the role of this pathway in the HPG axis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

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