Global gene expression profiles in skeletal muscle of monozygotic female twins discordant for hormone replacement therapy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Paula Ronkainen
PROVIDER: E-GEOD-21421 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Analysis of gene expression profiles in skeletal muscle tissue after long-term use of HRT. Networks of enriched processes in skeletal muscle responding to long-term use of estrogen-based HRT in comparison with women without any HRT in a genetically controlled setting were contructed. The association between the expression of specific biological processes and muscle composition or performance was tested. The hypothesis was that the differences in gene expression profiles reflect the known differences in muscle composition and performance.
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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
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Project description:Muscle mass and strength reduce during ageing with a steeper decline in women around the age of 50, which suggests that the menopausal transition is one of the mechanisms for age-induced neuromuscular deteriorations. At the moment, there is no clear explanation for the decline in muscle properties although both physical exercise and maintaining near premenopausal estrogen levels by hormonal replacement have been helpful in their preservation. However, the molecular consequences of both treatments in skeletal muscle are mostly unknown. The goal of this genome-wide study was to investigate the transcriptional networks through which power training (PT) comprising of jumping activities and estrogen containing hormone replacement therapy (HRT) may aid in the prevention of functional limitation ensued from insufficient muscle mass and physical performance after menopause. We used m. vastus lateralis samples obtained from postmenopausal women participating in a yearlong randomized double-blinded placebo-controlled trial with PT and HRT interventions. Muscle samples were available from eight PT, ten HRT and nine control women. Women in the PT group participated in a progressive PT program comprising mostly of jumping exercises for lower limbs with additional resistance exercises for the upper body. HRT intervention was double-blinded. All participants used either estradiol/noretisterone acetate preparation or placebo. Using statistical threshold p-value <0.05 and |fold change| >1.2 we identified 665 genes being differentially expressed among the studied 50-57-yr-old postmenopausal women. We used the hierarchical clustering method with extensive enrichment analysis in order to reveal enrichment of known GO or KEGG functional categories among co-regulated gene-clusters. In the enrichment analysis false discovery rate was set to be less than 15%. Transcription of “response to contraction”-, “insulin signaling”- and “adipocytokine signaling”-genes were upregulated by PT. Both PT and HRT were similarly effective on transcriptional regulation of glycolytic energy metabolism and calcium signaling. The HRT specifically affected “mitochondrion”-genes. In addition, we identified functional categories, such as “muscle development”, which were changed during the trial in all study groups. Our study revealed transcriptional changes in several functional categories in thigh muscle tissue of early postmenopausal women. The results emphasize that during the first years of the postmenopausal period, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle mass and performance. More specifically, our findings indicate that PT and HRT may function through improving energy metabolism, improving the response to contraction, preserving functionality of mitochondria and reducing reorganization of muscle tissue. Therefore these treatments are recommended for preservation of adequate muscle mass and function. 54 samples, which formed 3 study groups with 2 timepoints, i.e., 8 power training subjects, 10 hormone replacement subjects and 9 controls. 6 control subjects had replicated samples resulting in a total of 60 hybridizations.
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Project description:Muscle mass and strength reduce during ageing with a steeper decline in women around the age of 50, which suggests that the menopausal transition is one of the mechanisms for age-induced neuromuscular deteriorations. At the moment, there is no clear explanation for the decline in muscle properties although both physical exercise and maintaining near premenopausal estrogen levels by hormonal replacement have been helpful in their preservation. However, the molecular consequences of both treatments in skeletal muscle are mostly unknown. The goal of this genome-wide study was to investigate the transcriptional networks through which power training (PT) comprising of jumping activities and estrogen containing hormone replacement therapy (HRT) may aid in the prevention of functional limitation ensued from insufficient muscle mass and physical performance after menopause. We used m. vastus lateralis samples obtained from postmenopausal women participating in a yearlong randomized double-blinded placebo-controlled trial with PT and HRT interventions. Muscle samples were available from eight PT, ten HRT and nine control women. Women in the PT group participated in a progressive PT program comprising mostly of jumping exercises for lower limbs with additional resistance exercises for the upper body. HRT intervention was double-blinded. All participants used either estradiol/noretisterone acetate preparation or placebo. Using statistical threshold p-value <0.05 and |fold change| >1.2 we identified 665 genes being differentially expressed among the studied 50-57-yr-old postmenopausal women. We used the hierarchical clustering method with extensive enrichment analysis in order to reveal enrichment of known GO or KEGG functional categories among co-regulated gene-clusters. In the enrichment analysis false discovery rate was set to be less than 15%. Transcription of “response to contraction”-, “insulin signaling”- and “adipocytokine signaling”-genes were upregulated by PT. Both PT and HRT were similarly effective on transcriptional regulation of glycolytic energy metabolism and calcium signaling. The HRT specifically affected “mitochondrion”-genes. In addition, we identified functional categories, such as “muscle development”, which were changed during the trial in all study groups. Our study revealed transcriptional changes in several functional categories in thigh muscle tissue of early postmenopausal women. The results emphasize that during the first years of the postmenopausal period, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle mass and performance. More specifically, our findings indicate that PT and HRT may function through improving energy metabolism, improving the response to contraction, preserving functionality of mitochondria and reducing reorganization of muscle tissue. Therefore these treatments are recommended for preservation of adequate muscle mass and function.
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