ArticleMolecular and cellular biology2017
Feminization of Male Mouse Liver by Persistent Growth Hormone Stimulation: Activation of Sex-Biased Transcriptional Networks and Dynamic Changes in Chromatin States.
Article in Molecular and cellular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- The cross-talk between leptin and circadian rhythm signaling proteins in physiological processes: a systematic review.Molecular biology reports · 2023Pooled it
- Disease-associated mutations in the STAT5B SH2 domain reprogram hepatic cholesterol and lipid metabolism.Endocrinology · 2026Article
- Androgen excess uncouples circulating and hepatic lipid homeostasis in females on a high-calorie diet.Journal of lipid research · 2026Article
- Integrated chromatin and transcriptomic profiling reveals sex-specific mechanisms of gene regulation in hepatic nutrient responses.PLoS biology · 2026Article
- HDI-STARR-seq Identifies Functional GH-regulated Sex-Biased Hepatocyte Enhancers Linked to Liver Metabolism and Disease.bioRxiv : the preprint server for biology · 2026Article
- GH-resistant (Laron) mice: gene therapy with a liver-specific GH receptor causes unbalanced upregulation of female-biased and growth-related genes.Frontiers in endocrinology · 2026Article
- Sex-Specific transcriptomic changes in adipose tissue following adult-onset disruption of growth hormone receptor.Pituitary · 2025Article
- Disease-associated mutations in the STAT5B SH2 domain reprogram hepatic cholesterol and lipid metabolism.bioRxiv : the preprint server for biology · 2025Article
- Human Hepatocytes in Experimental Steatosis: Influence of Donor Sex and Sex Hormones.Biomedicines · 2025Article
- Single Nucleus MultiOmics Links Novel Transcription Factor Motifs to Murine Hepatic Sex Differences in Chromatin Accessibility and Metabolic Dysfunction-Associated Steatotic Liver Disease.bioRxiv : the preprint server for biology · 2025Article
- Genome-Wide Identification and Expression Analysis of the STAT Family in Reeve's Turtle (Mauremys reevesii).Biochemical genetics · 2025Article
- Widespread discordance between mRNA expression, protein abundance andbioRxiv : the preprint server for biology · 2025Article
- Survey of gene, lncRNA and transposon transcription patterns in four mouse organs highlights shared and organ-specific sex-biased regulation.Genome biology · 2025Article
- Developmental programming: Sex-specific effects of prenatal exposure to a real-life mixture of environmental chemicals on liver function and transcriptome in sheep.Environmental pollution (Barking, Essex : 1987) · 2025Article
- Maternal Exposure to Ozone During Implantation Promotes a Feminized Transcriptomic Profile in the Male Adolescent Liver.Endocrinology · 2025Article
- Tmem263 deletion disrupts the GH/IGF-1 axis and causes dwarfism and impairs skeletal acquisition.eLife · 2024Article
- Modifications of the GH Axis Reveal Unique Sexually Dimorphic Liver Signatures forJournal of the Endocrine Society · 2024Article
- Article
- Plasma Growth Hormone Pulses Induce Male-biased Pulsatile Chromatin Opening and Epigenetic Regulation in Adult Mouse Liver.bioRxiv : the preprint server for biology · 2023Article
- Tmem263 deletion disrupts the GH/IGF-1 axis and causes dwarfism and impairs skeletal acquisition.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Sex-dependent pituitary growth hormone (GH) secretory profiles-pulsatile in males and persistent in females-regulate the sex-biased, STAT5-dependent expression of hundreds of genes in mouse liver, imparting sex differences in hepatic drug/lipid metabolism and disease risk. Here, we examine transcriptional and epigenetic changes induced by continuous GH infusion (cGH) in male mice, which rapidly feminizes the temporal profile of liver STAT5 activity. cGH repressed 86% of male-biased genes and induced 68% of female-biased genes within 4 days; however, several highly female-specific genes showed weak or no feminization, even after 14 days of cGH treatment. Female-biased genes already in an active chromatin state in male liver generally showed early cGH responses; genes in an inactive chromatin state often responded late. Early cGH-responsive genes included those encoding two GH/STAT5-regulated transcriptional repressors: male-biased BCL6, which was repressed, and female-specific CUX2, which was induced. Male-biased genes activated by STAT5 and/or repressed by CUX2 were enriched for early cGH repression. Female-biased BCL6 targets were enriched for early cGH derepression. Changes in sex-specific chromatin accessibility and histone modifications accompanied these cGH-induced sex-biased gene expression changes. Thus, the temporal, sex-biased gene responses to persistent GH stimulation are dictated by GH/STAT5-regulated transcription factors arranged in a hierarchical network and by the dynamics of changes in sex-biased epigenetic states.
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