Estrogen-dependent gene expression in skeletal muscle
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE134409 | GEO | 2020/11/05
REPOSITORIES: GEO
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Project description:The female sex hormone estrogens plays a critical role in maintaining muscle mass and muscle stem cell (MuSCs) functions. However, it is still unclear about downstream pathways of estrogens including its receptors that are expressed in both skeletal muscle tissue and MuSCs. To study the specific role of estrogen receptor β (ERβ), one of two main types of estrogen receptors, in skeletal muscle and MuSCs, we generated muscle-specific ERβ-knockout (mKO) mice and muscle stem cell-specific ERβ-knockout (scKO) mice. Here, we show that muscle-specific ERβ-deficient induced decreased muscle strength and fast-type muscle mass in young female mice. Furthermore, muscle stem cell-specific ERβ-deficient young female mice but not male exhibited impaired muscle regeneration ability after acute muscle injury, accompanied by a decreased proliferation rate of muscle stem cells. RNA sequencing analysis showed that the loss of ERβ in muscle stem cells changes the expression of cell cycle associated genes and niche component factors including laminin and collagen. Thus, our characterization of mKO and scKO mice indicate that the estrogen-ERβ pathway is a sex-specific regulatory mechanism that controls both skeletal muscle mass and the proliferation of muscle stem cell in females and could be of importance in a therapeutic context.
2020-03-31 | GSE135837 | GEO
Project description:Estrogen-dependent gene expression in skeletal muscle
| PRJNA555116 | ENA
Project description:Modification of Gene Expression of Skeletal Muscle in Response to postmenopause with or without Hormone Replacement Therapy. Even though menopause is often accompanied with first signs of age-associated changes in muscle structure and function, the effects of hormone replacement therapy (HRT) or menopause-related decline in estrogen production in the muscles of postmenopausal women is not well understood. We have used a randomized double-blinded study design together with an explorative microarray experiment to characterize possible effects of continuous, combined HRT and estrogen deprivation on the skeletal muscle of fifteen early postmenopausal women from which 10 used HRT and 5 used placebo for 12-months in a douple-blinded design. Keywords: time course analysis from HRT users and non-users comparison of gene expression in skeletal muscle of healthy postmenopausel women using HRT (n=10) vs not-using HRT (n=5)
2007-11-12 | E-GEOD-6348 | biostudies-arrayexpress
Project description:Modification of Gene Expression of Skeletal Muscle in Response to postmenopause with or without Hormone Replacement Therapy. Even though menopause is often accompanied with first signs of age-associated changes in muscle structure and function, the effects of hormone replacement therapy (HRT) or menopause-related decline in estrogen production in the muscles of postmenopausal women is not well understood. We have used a randomized double-blinded study design together with an explorative microarray experiment to characterize possible effects of continuous, combined HRT and estrogen deprivation on the skeletal muscle of fifteen early postmenopausal women from which 10 used HRT and 5 used placebo for 12-months in a douple-blinded design. Keywords: time course analysis from HRT users and non-users
2007-11-12 | GSE6348 | GEO
Project description:The loss of skeletal muscle strength mid-life in females is associated with the decline of estrogen. Here, we questioned how estrogen deficiency might impact the overall skeletal muscle phosphoproteome after contraction, as force production induces phosphorylation of several muscle proteins. Phosphoproteomic analyses of the tibialis anterior muscle after contraction in two mouse models of estrogen deficiency, ovariectomy (Ovariectomized [Ovx] vs Sham) and natural aging-induced ovarian senescence (Older Adult [OA] vs Young Adult [YA]), identified a total of 2,593 and 3,507 phosphopeptides in Ovx/Sham and OA/YA datasets, respectively. Further analysis of estrogen deficiency-associated proteins and phosphosites identified 66 proteins and 21 phosphosites from both datasets. Of these, 4 estrogen deficiency-associated proteins and 4 estrogen deficiency-associated phosphosites were significant and differentially phosphorylated or regulated, respectively. Comparative analyses between Ovx/Sham and OA/YA using Ingenuity Pathway Analysis (IPA) found parallel patterns of inhibition and activation across IPA-defined canonical signaling pathways and physiological functional analysis, which were similarly observed in downstream GO, KEGG, and Reactome pathway overrepresentation analysis pertaining to muscle structural integrity and contraction, including AMPK and calcium signaling. IPA Upstream regulator analysis identified MAPK1 and PRKACA as candidate kinases and calcineurin as a candidate phosphatase sensitive to estrogen. Our findings highlight key molecular signatures and pathways in contracted muscle suggesting that the similarities identified across both datasets could elucidate molecular mechanisms that may contribute to skeletal muscle strength loss due to estrogen deficiency.
2023-09-01 | PXD035171 | Pride
Project description:Shatavari is a herbal dietary supplement that may increase skeletal muscle strength in younger and older adults. Shatavari contains compounds with both estradiol-like and antioxidant properties, which could enhance muscle function. Postmenopausal women may derive the greatest benefit, as estrogen deficiency adversely impacts skeletal muscle function. However, mechanistic insights are limited and the effects of shatavari on muscle function require further characterization. In this randomised, double-blind trial, 17 young (23 ±5yr) and 22 older (63±5yr) women completed an eight-week leg resistance training programme. They consumed either a placebo or shatavari (1000mg/d, equivalent to 26,500 mg/d fresh weight) supplement throughout. Pre and post training, measures of leg strength, neuromuscular function and vastus lateralis (VL) biopsies were obtained. Tandem-mass-tagged VL proteomic analyses were performed. Additionally, resistance training (RT) is the gold standard intervention for ameliorating sarcopenia. Outstanding mechanistic questions remain regarding the malleability of the molecular determinants of skeletal muscle function in older age. Discovery proteomics can expand such knowledge. We further aimed to compare the effect of RT on the skeletal muscle proteome and neuromuscular function (NMF) in older and younger women.
2024-10-22 | PXD056507 | Pride
Project description:Decreased insulin availability and high blood glucose levels, the hallmark features of poorly controlled diabetes, drive disease progression and are associated with decreased skeletal muscle mass. We have shown that mice with -cell dysfunction and normal insulin sensitivity have decreased skeletal muscle mass. This project asks how insulin deficiency impacts on the structure and function of the remaining skeletal muscle in these animals. Methods: Skeletal muscle function was determined by measuring exercise capacity and specific muscle strength prior to and after insulin supplementation for 28 days in 12-week-old mice with conditional -cell deletion of the ATP binding cassette transporters ABCA1 and ABCG1 (β-DKO mice). Abca1 and Abcg1 floxed (fl/fl) mice were used as controls. RNAseq was used to quantify changes in transcripts in soleus and extensor digitorum longus muscles. Skeletal muscle and mitochondrial morphology were assessed by transmission electron microscopy. Myofibrillar Ca2+ sensitivity and maximum isometric single muscle fibre force were assessed using MyoRobot biomechatronics technology. Results: RNA transcripts were significantly altered in β-DKO mice compared to fl/fl controls (32 in extensor digitorum longus and 412 in soleus). Exercise capacity and muscle strength were significantly decreased in β-DKO mice compared to fl/fl controls (p = 0.012), and a loss of structural integrity was also observed in skeletal muscle from the β-DKO mice. Supplementation of β-DKO mice with insulin restored muscle integrity, strength and expression of 13 and 16 of the dysregulated transcripts in and extensor digitorum longus and soleus muscles, respectively. Conclusions: Insulin insufficiency due to -cell dysfunction perturbs the structure and function of skeletal muscle. These adverse effects are rectified by insulin supplementation.
2023-09-26 | E-MTAB-13315 | biostudies-arrayexpress
Project description:The functional importance of gene enhancers in regulated gene expression is well established. In addition to widespread transcription of long non-coding RNA (ncRNA) transcripts in mammalian cells, bidirectional ncRNAs referred to as eRNAs are present on enhancers. However, it has remained unclear whether these eRNAs are functional, or merely a reflection of enhancer activation. Here, we report that 17 ?-estradiol (E2)-bound estrogen receptor alpha (ER?) on enhancers causes a global increase in eRNA transcription on enhancers adjacent to E2 upregulated coding genes. These induced eRNAs, as functional transcripts, appear to exert important roles for the observed ligand-dependent induction of target coding genes, causing an increased strength of specific enhancer:promoter looping initiated by ER? binding. Cohesin, present on many ER?-regulated enhancers even prior to ligand treatment, apparently contributes to E2-dependent gene activation by stabilizing E2/ER?/eRNA-induced enhancer:promoter looping. Our data indicate that eRNAs are likely to exert important functions in many regulated programs of gene transcription. The ChIP-seqs in this study measure the binding landscape of master transcription regulator of estrogen signaling - ER?, together with common histone marks including H3K27ac and H3K4me1 in MCF7 cells. These data serve as the basis to understand the enhancer map and subsequent analysis of eRNA expression using GRO-seq. The GRO-seq measures the trancription of nascent RNAs in the genome. From MCF7 cells treated with veichle or estrodial, we could identify estrogen-regulated eRNAs and subsequently could study their functions.
2013-06-04 | E-GEOD-45822 | biostudies-arrayexpress
Project description:Estrogen receptor β regulates skeletal muscle mass and muscle stem cell proliferation in young female mice
| PRJNA560238 | ENA
Project description:In women, estrogen deficiency after menopause frequently accelerates osteoclastic bone resorption, leading to osteoporosis, the most common skeletal disorder. However, mechanisms underlying osteoporosis resulting from estrogen deficiency remain largely unknown. To gain new insights into the impact of estrogen on bone marrow B cells, we used high-throughput sequencing to analyze global estrogen transcriptional networks in WT bone marrow B cells under hypoxic culture.
2022-02-24 | GSE163849 | GEO