Genomics of sex hormone receptor signaling in hepatic sexual dimorphism

Daoshan Zheng, Xiao Wang, Per Antonson, Jan Åke Gustafsson, Zhaoyu Li

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The liver plays a crucial role in a variety of physiological processes. Sexual dimorphism is markedly defined in liver disorders, such as fatty liver diseases and liver cancer, but barely addressed in the normal liver. Distinct sex hormone signaling between male and female livers is the major driving factor for hepatic sexual dimorphism. Over 6000 genes are differently expressed between male and female livers in mice. Here we address how sex hormone receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), mediate sexually dimorphic gene expression in mouse livers. We identified 5192 ERα target genes and 4154 AR target genes using ChIP-Seq. Using liver-specific ERα or AR knockout mice, we further identified direct and functional target genes of ERα (123 genes) and AR (151 genes) that contribute to hepatic sexual dimorphism. We also found that the most significant sexually dimorphic gene expression was initiated at birth by comparing hepatic gene expression data from the embryonic stage E10.5 to the postnatal stage P60 during liver development. Overall, our study indicates that sex hormone receptor signaling drives sexual dimorphism of hepatic gene expression throughout liver development.

Original languageEnglish (US)
JournalMolecular and Cellular Endocrinology
DOIs
StateAccepted/In press - Dec 16 2016

Fingerprint

Gonadal Steroid Hormones
Genomics
Sex Characteristics
Liver
Estrogen Receptor alpha
Genes
Androgen Receptors
Gene expression
Gene Expression
Physiological Phenomena
Fatty Liver
Liver Neoplasms
Knockout Mice
Liver Diseases
Parturition

Keywords

  • Androgen receptor (AR)
  • Estrogen receptor alpha (ERα)
  • Mouse liver
  • Sexual dimorphism

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Genomics of sex hormone receptor signaling in hepatic sexual dimorphism. / Zheng, Daoshan; Wang, Xiao; Antonson, Per; Gustafsson, Jan Åke; Li, Zhaoyu.

In: Molecular and Cellular Endocrinology, 16.12.2016.

Research output: Contribution to journalArticle

Zheng, Daoshan ; Wang, Xiao ; Antonson, Per ; Gustafsson, Jan Åke ; Li, Zhaoyu. / Genomics of sex hormone receptor signaling in hepatic sexual dimorphism. In: Molecular and Cellular Endocrinology. 2016.
@article{0261343eeed549e7989cead030bfe42e,
title = "Genomics of sex hormone receptor signaling in hepatic sexual dimorphism",
abstract = "The liver plays a crucial role in a variety of physiological processes. Sexual dimorphism is markedly defined in liver disorders, such as fatty liver diseases and liver cancer, but barely addressed in the normal liver. Distinct sex hormone signaling between male and female livers is the major driving factor for hepatic sexual dimorphism. Over 6000 genes are differently expressed between male and female livers in mice. Here we address how sex hormone receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), mediate sexually dimorphic gene expression in mouse livers. We identified 5192 ERα target genes and 4154 AR target genes using ChIP-Seq. Using liver-specific ERα or AR knockout mice, we further identified direct and functional target genes of ERα (123 genes) and AR (151 genes) that contribute to hepatic sexual dimorphism. We also found that the most significant sexually dimorphic gene expression was initiated at birth by comparing hepatic gene expression data from the embryonic stage E10.5 to the postnatal stage P60 during liver development. Overall, our study indicates that sex hormone receptor signaling drives sexual dimorphism of hepatic gene expression throughout liver development.",
keywords = "Androgen receptor (AR), Estrogen receptor alpha (ERα), Mouse liver, Sexual dimorphism",
author = "Daoshan Zheng and Xiao Wang and Per Antonson and Gustafsson, {Jan {\AA}ke} and Zhaoyu Li",
year = "2016",
month = "12",
day = "16",
doi = "10.1016/j.mce.2017.05.025",
language = "English (US)",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Genomics of sex hormone receptor signaling in hepatic sexual dimorphism

AU - Zheng, Daoshan

AU - Wang, Xiao

AU - Antonson, Per

AU - Gustafsson, Jan Åke

AU - Li, Zhaoyu

PY - 2016/12/16

Y1 - 2016/12/16

N2 - The liver plays a crucial role in a variety of physiological processes. Sexual dimorphism is markedly defined in liver disorders, such as fatty liver diseases and liver cancer, but barely addressed in the normal liver. Distinct sex hormone signaling between male and female livers is the major driving factor for hepatic sexual dimorphism. Over 6000 genes are differently expressed between male and female livers in mice. Here we address how sex hormone receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), mediate sexually dimorphic gene expression in mouse livers. We identified 5192 ERα target genes and 4154 AR target genes using ChIP-Seq. Using liver-specific ERα or AR knockout mice, we further identified direct and functional target genes of ERα (123 genes) and AR (151 genes) that contribute to hepatic sexual dimorphism. We also found that the most significant sexually dimorphic gene expression was initiated at birth by comparing hepatic gene expression data from the embryonic stage E10.5 to the postnatal stage P60 during liver development. Overall, our study indicates that sex hormone receptor signaling drives sexual dimorphism of hepatic gene expression throughout liver development.

AB - The liver plays a crucial role in a variety of physiological processes. Sexual dimorphism is markedly defined in liver disorders, such as fatty liver diseases and liver cancer, but barely addressed in the normal liver. Distinct sex hormone signaling between male and female livers is the major driving factor for hepatic sexual dimorphism. Over 6000 genes are differently expressed between male and female livers in mice. Here we address how sex hormone receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), mediate sexually dimorphic gene expression in mouse livers. We identified 5192 ERα target genes and 4154 AR target genes using ChIP-Seq. Using liver-specific ERα or AR knockout mice, we further identified direct and functional target genes of ERα (123 genes) and AR (151 genes) that contribute to hepatic sexual dimorphism. We also found that the most significant sexually dimorphic gene expression was initiated at birth by comparing hepatic gene expression data from the embryonic stage E10.5 to the postnatal stage P60 during liver development. Overall, our study indicates that sex hormone receptor signaling drives sexual dimorphism of hepatic gene expression throughout liver development.

KW - Androgen receptor (AR)

KW - Estrogen receptor alpha (ERα)

KW - Mouse liver

KW - Sexual dimorphism

UR - http://www.scopus.com/inward/record.url?scp=85020483945&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020483945&partnerID=8YFLogxK

U2 - 10.1016/j.mce.2017.05.025

DO - 10.1016/j.mce.2017.05.025

M3 - Article

C2 - 28554805

AN - SCOPUS:85020483945

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

ER -