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)
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
Project description:Modification of Gene Expression of Skeletal Muscle in Response to postmenopause with or without Hormone Replacement Therapy. Test samples randomly selected from a larger study in order to verify the validity of microarray experiment. Keywords: time course analysis from HRT users and non-users
Project description:Women’s aging is characterized by menopausal loss of ovarian function, which has been suggested as a contributing factor to aging-related muscle deterioration and predisposes to the metabolic dysfunctions. However, the underlying molecular mechanisms have remained unknown. To identify mechanisms, we utilized muscle samples from 24 pre- and postmenopausal women, established proteome-wide profiles and identified upstream regulators and downstream cellular pathways associated with the differences in age, menopausal status and use of hormone replacement therapy (HRT). None of the premenopausal women used hormonal medication while the postmenopausal women were monozygotic twin-sister pairs who were either current HRT users or had never used HRT. The proteomic analyses resulted in the quantification of 762 muscle proteins of which 158 were for the first time associated with female muscle aging. The Ingenuity Pathway Analysis pinpointed 17β-estradiol as a potential upstream regulator of the observed differences in the major downstream pathways including dysregulated cell death and glycolysis pathways. The results increase knowledge on the factors related to skeletal muscle signaling and aging. This is of importance, since the role of female sex hormones in the regulation of muscle cell signaling has been under appreciated and scarcely studied as compared to vast amount of data on male sex hormones and skeletal muscle. Our results clearly demonstrate the also female sex hormones and HRT should be considered as potential active players and an intervention targets to promote women’s muscular health.
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.
Project description:The American Women's Health Initiative study published in July 2002 caused considerable concern among hormone replacement therapy (HRT) users and prescribers in many countries. This study is an exploratory research comparing the genome wide expression profile in whole blood samples according to HRT use. Within the Norwegian Women and Cancer study, 100 postmenopausal women (50 HRT users and 50 non-HRT users) born between 1943 and 1949 with normal to high body mass index and no other medication use were selected. After total RNA extraction, amplification and labelling, the samples were hybridized together with a common reference (Universal human reference RNA, Stratagen) to Agilent Human 1A oligoarrays (G4110b, Agilent Technologies, Palo Alto, CA) containing 20,173 unique genes. Differentially expressed genes were used to build a classifier using the nearest shrunken centroids method (PAM). Then, we tested the significant changes in single genes by different methods like t-test, Significance Analysis of Microarrays (SAM) and Bayesian ANOVA analysis (BAM). Results did not reveal any distinct gene list which predicted accurately HRT exposure (error rate = 0.45). Classifier performance slightly improved (error rate = 0.29) including only women who were using continuous combined HRT treatment. According to the small amplitude of expression alterations observed after HRT use in whole blood, large sample sizes are needed to identify significant single genes differentially expressed. However, significant enrichments in biologic process of genes with small changes after HRT use were observed (e.g. receptor and transporter activities, immune response, frizzled signalling pathway, actin filament organization, glycogen metabolism). Experiment Overall Design: Indirect design with Stratagene reference Experiment Overall Design: 47 non HRT users and 42 HRT users Experiment Overall Design: No technical replicates
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. Total RNA obtained from muscle biopsies (vastus lateralis) from genetically identical female twin pairs (n=11 pairs) of which one sister is a user of postmenopausal, estrogen-based HRT (n=11), while the other is a never-user (n=11).
Project description:The American Women’s Health Initiative study published in July 2002 caused considerable concern among hormone replacement therapy (HRT) users and prescribers in many countries. This study is an exploratory research comparing the genome wide expression profile in whole blood samples according to HRT use. Within the Norwegian Women and Cancer study, 100 postmenopausal women (50 HRT users and 50 non-HRT users) born between 1943 and 1949 with normal to high body mass index and no other medication use were selected. After total RNA extraction, amplification and labelling, the samples were hybridized together with a common reference (Universal human reference RNA, Stratagen) to Agilent Human 1A oligoarrays (G4110b, Agilent Technologies, Palo Alto, CA) containing 20,173 unique genes. Differentially expressed genes were used to build a classifier using the nearest shrunken centroids method (PAM). Then, we tested the significant changes in single genes by different methods like t-test, Significance Analysis of Microarrays (SAM) and Bayesian ANOVA analysis (BAM). Results did not reveal any distinct gene list which predicted accurately HRT exposure (error rate = 0.45). Classifier performance slightly improved (error rate = 0.29) including only women who were using continuous combined HRT treatment. According to the small amplitude of expression alterations observed after HRT use in whole blood, large sample sizes are needed to identify significant single genes differentially expressed. However, significant enrichments in biologic process of genes with small changes after HRT use were observed (e.g. receptor and transporter activities, immune response, frizzled signalling pathway, actin filament organization, glycogen metabolism). Keywords: gene expression profile and exposure