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dc.contributor.authorPöllänen, Eija
dc.contributor.authorRonkainen, Paula
dc.contributor.authorHorttanainen, Mia
dc.contributor.authorTakala, Timo
dc.contributor.authorPuolakka, Jukka
dc.contributor.authorSuominen, Harri
dc.contributor.authorSipilä, Sarianna
dc.contributor.authorKovanen, Vuokko
dc.date.accessioned2017-05-19T10:05:43Z
dc.date.available2017-05-19T10:05:43Z
dc.date.issued2010
dc.identifier.citationPöllänen, E., Ronkainen, P., Horttanainen, M., Takala, T., Puolakka, J., Suominen, H., Sipilä, S., & Kovanen, V. (2010). Effects of combined hormone replacement therapy or its effective agents on the IGF-1 pathway in skeletal muscle. <i>Growth Hormone and IGF Research</i>, <i>20</i>(5), 372-379. <a href="https://doi.org/10.1016/j.ghir.2010.07.003" target="_blank">https://doi.org/10.1016/j.ghir.2010.07.003</a>
dc.identifier.otherCONVID_19568967
dc.identifier.otherTUTKAID_40895
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/54036
dc.description.abstractObjectives To investigate the effects of combined hormone replacement therapy (HRT) and its effective agents on the IGF-1 signaling pathway. Design and methods To examine the effects of HRT on skeletal muscle in vivo, we utilized pre- and post-intervention samples from a randomized double blinded trial with 50–57-year-old women. The intervention included the year-long use of either HRT preparation (2 mg 17β-estradiol, E2; 1 mg norethisterone acetate, NETA, n = 10) or placebo (CO, n = 9). Microarray technology and quantitative PCR (qPCR) were used to study the expression of insulin-like growth factor I (IGF-1) and its splice variants as well as IGF-1 receptor, Akt1, mTOR, FOXO1, FOXO3, atrogin, estrogen receptors and androgen receptor in muscle samples. Serum concentrations of IGF-1, E2 and testosterone were measured. C2C12 myotubes were fed with E2 or NETA followed by analyzing the expression of essentially the same gene transcripts as in human samples by qPCR and phosphorylation of Akt and mTOR by Western blotting. Results The gene expression of IGF-1 and its splice variant, IGF-1Ec (also known as the mechano growth factor or MGF), mTOR, FOXO3, and AR was up-regulated among the HRT users compared to the CO (P < 0.05), while Akt1 was down-regulated (P < 0.05). The change in the level of IGF-1Ec transcript correlated positively with muscle size at post-intervention (r = 0.5, P < 0.05). In C2C12 myotubes, no statistically significant effects of either E2 or NETA at the level of gene transcripts studied were identified. The amount of phosphorylated Akt appeared to respond to NETA, albeit the response was not statistically significant. Phosphorylation of mTOR did not respond to either of the treatments. Conclusion Year-long postmenopausal HRT was found to affect the expression of the genes along the IGF-1 signaling cascade reflecting the higher muscle mass compared to the CO women. By using cell culture model we were, however, unable to confirm the possible differential role of E2 and NETA. It appears that the synchronous presence of both effective agents of the HRT or the presence of yet unidentified microenvironmental factors providing proper paracrine signals naturally existing in the intact muscle tissue is critical for appropriate signaling via sex steroid-IGF-1 axis to occur.
dc.language.isoeng
dc.publisherChurchill Livingstone
dc.relation.ispartofseriesGrowth Hormone and IGF Research
dc.subject.otherhormonikorvaushoito
dc.subject.otherIGF-1 signalointi
dc.subject.otherluurankolihas
dc.subject.othernoretisteroniasetaatti
dc.subject.otherpostmenopausaalinen nainen
dc.subject.otherHormone replacement therapy
dc.subject.otherIGF-1 signaling
dc.subject.otherskeletal muscle
dc.subject.othernorethisterone acetate
dc.subject.otherpostmenopausal women
dc.titleEffects of combined hormone replacement therapy or its effective agents on the IGF-1 pathway in skeletal muscle
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201705182404
dc.contributor.laitosTerveystieteiden laitosfi
dc.contributor.laitosDepartment of Health Sciencesen
dc.contributor.oppiaineGerontologia ja kansanterveysfi
dc.contributor.oppiaineGerontologian tutkimuskeskusfi
dc.contributor.oppiaineGerontology and Public Healthen
dc.contributor.oppiaineGerontology Research Centeren
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.date.updated2017-05-18T09:15:05Z
dc.type.coarjournal article
dc.description.reviewstatuspeerReviewed
dc.format.pagerange372-379
dc.relation.issn1096-6374
dc.relation.numberinseries5
dc.relation.volume20
dc.type.versionacceptedVersion
dc.rights.copyright© 2010 Growth Hormone Research Society. This is a final draft version of an article whose final and definitive form has been published by Elsevier. Published in this repository with the kind permission of the publisher.
dc.rights.accesslevelopenAccessfi
dc.subject.ysoestradioli
jyx.subject.urihttp://www.yso.fi/onto/yso/p19425
dc.relation.doi10.1016/j.ghir.2010.07.003


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