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Hum Mol Genet. 2017 Sep 15;26(18):3585-3599. doi: 10.1093/hmg/ddx246.

Gene expression profiling of puberty-associated genes reveals abundant tissue and sex-specific changes across postnatal development.

Author information

1
Program in Genetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
2
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
3
Department of Gene Technology, Tallinn University of Technology, 12616 Tallinn, Estonia.
4
Department of Computer Science, University of Toronto, Toronto, ON M5S 2E5, Canada.
5
Division of Endocrinology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
6
Departments of Paediatrics and Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Abstract

The timing of human puberty is highly variable, sexually dimorphic, and associated with adverse health outcomes. Over 20 genes carrying rare mutations have been identified in known pubertal disorders, many of which encode critical components of the hypothalamic-pituitary-gonadal (HPG) axis. Recent genome-wide association studies (GWAS) have identified more than 100 candidate genes at loci associated with age at menarche or voice breaking in males. We know little about the spatial, temporal or postnatal expression patterns of the majority of these puberty-associated genes. Using a high-throughput and sensitive microfluidic quantitative PCR strategy, we profiled the gene expression patterns of the mouse orthologs of 178 puberty-associated genes in male and female mouse HPG axis tissues, the pineal gland, and the liver at five postnatal ages spanning the pubertal transition. The most dynamic gene expression changes were observed prior to puberty in all tissues. We detected known and novel tissue-enhanced gene expression patterns, with the hypothalamus expressing the largest number of the puberty-associated genes. Notably, over 40 puberty-associated genes in the pituitary gland showed sex-biased gene expression, most of which occurred peri-puberty. These sex-biased genes included the orthologs of candidate genes at GWAS loci that show sex-discordant effects on pubertal timing. Our findings provide new insight into the expression of puberty-associated genes and support the possibility that the pituitary plays a role in determining sex differences in the timing of puberty.

PMID:
28911201
PMCID:
PMC5886205
DOI:
10.1093/hmg/ddx246
[Indexed for MEDLINE]
Free PMC Article

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