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A microarray study on the effect of four hormone therapy regimens on gene transcription in whole blood from healthy postmenopausal women.
Thromb Res. 2012 Jul; 130(1):45-51.TR

Abstract

BACKGROUND

Postmenopausal hormone therapy is associated with many diseases and conditions, e.g., cardiovascular diseases and asthma, but the underlying molecular mechanisms are incompletely understood. The aim of the current study was to investigate the effect of four different postmenopausal hormone therapy regimens on gene transcription.

MATERIALS AND METHODS

Twenty-four healthy postmenopausal women (six women in four groups) were randomly allocated to conventional-dose 17β-estradiol/norethisterone acetate (NETA), low-dose 17β-estradiol/NETA, tibolone, or raloxifene hydrochloride. RNA was isolated from whole blood before and after 6weeks of treatment. The changes in mRNA were assessed with a microarray chip.

RESULTS

The genes FKBP5, IL13RA1, TPST1, and TLR2 were up-regulated and among the most significantly changed genes in the groups treated with conventional-dose 17β-estradiol/NETA and tibolone. Up-regulation of TPST1 was associated with reduction of tissue factor pathway inhibitor in plasma. Nine biological pathways were associated with conventional-dose 17β-estradiol/NETA, most significantly the pathways for asthma, toll-like receptor signaling, cell adhesion molecules, and MAPK signaling. Transcriptional changes with false discovery rate below 0.10 were found in 10 genes in the conventional-dose 17β-estradiol/NETA group, 7 genes in the tibolone group, and zero genes in the women on low-dose 17β-estradiol/NETA. No genes or pathways were associated with raloxifene treatment.

CONCLUSIONS

The difference between low-dose and conventional-dose17β-estradiol/NETA indicates an effect of dose on transcriptional response. Several genes and pathways related to cell adhesion molecules and immunity related cell surface receptors were influenced by conventional-dose 17β-estradiol/NETA.

Authors+Show Affiliations

Department of Haematology, Oslo University Hospital, Oslo, Norway. a.e.a.dahm@medisin.uio.noNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22217510

Citation

Dahm, Anders E A., et al. "A Microarray Study On the Effect of Four Hormone Therapy Regimens On Gene Transcription in Whole Blood From Healthy Postmenopausal Women." Thrombosis Research, vol. 130, no. 1, 2012, pp. 45-51.
Dahm AE, Eilertsen AL, Goeman J, et al. A microarray study on the effect of four hormone therapy regimens on gene transcription in whole blood from healthy postmenopausal women. Thromb Res. 2012;130(1):45-51.
Dahm, A. E., Eilertsen, A. L., Goeman, J., Olstad, O. K., Ovstebø, R., Kierulf, P., Mowinckel, M. C., Skretting, G., & Sandset, P. M. (2012). A microarray study on the effect of four hormone therapy regimens on gene transcription in whole blood from healthy postmenopausal women. Thrombosis Research, 130(1), 45-51. https://doi.org/10.1016/j.thromres.2011.12.009
Dahm AE, et al. A Microarray Study On the Effect of Four Hormone Therapy Regimens On Gene Transcription in Whole Blood From Healthy Postmenopausal Women. Thromb Res. 2012;130(1):45-51. PubMed PMID: 22217510.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A microarray study on the effect of four hormone therapy regimens on gene transcription in whole blood from healthy postmenopausal women. AU - Dahm,Anders E A, AU - Eilertsen,Anette L, AU - Goeman,Jelle, AU - Olstad,Ole Kristoffer, AU - Ovstebø,Reidun, AU - Kierulf,Peter, AU - Mowinckel,Marie-Christine, AU - Skretting,Grethe, AU - Sandset,Per Morten, Y1 - 2012/01/02/ PY - 2011/09/27/received PY - 2011/11/09/revised PY - 2011/12/02/accepted PY - 2012/1/6/entrez PY - 2012/1/6/pubmed PY - 2012/10/2/medline SP - 45 EP - 51 JF - Thrombosis research JO - Thromb. Res. VL - 130 IS - 1 N2 - BACKGROUND: Postmenopausal hormone therapy is associated with many diseases and conditions, e.g., cardiovascular diseases and asthma, but the underlying molecular mechanisms are incompletely understood. The aim of the current study was to investigate the effect of four different postmenopausal hormone therapy regimens on gene transcription. MATERIALS AND METHODS: Twenty-four healthy postmenopausal women (six women in four groups) were randomly allocated to conventional-dose 17β-estradiol/norethisterone acetate (NETA), low-dose 17β-estradiol/NETA, tibolone, or raloxifene hydrochloride. RNA was isolated from whole blood before and after 6weeks of treatment. The changes in mRNA were assessed with a microarray chip. RESULTS: The genes FKBP5, IL13RA1, TPST1, and TLR2 were up-regulated and among the most significantly changed genes in the groups treated with conventional-dose 17β-estradiol/NETA and tibolone. Up-regulation of TPST1 was associated with reduction of tissue factor pathway inhibitor in plasma. Nine biological pathways were associated with conventional-dose 17β-estradiol/NETA, most significantly the pathways for asthma, toll-like receptor signaling, cell adhesion molecules, and MAPK signaling. Transcriptional changes with false discovery rate below 0.10 were found in 10 genes in the conventional-dose 17β-estradiol/NETA group, 7 genes in the tibolone group, and zero genes in the women on low-dose 17β-estradiol/NETA. No genes or pathways were associated with raloxifene treatment. CONCLUSIONS: The difference between low-dose and conventional-dose17β-estradiol/NETA indicates an effect of dose on transcriptional response. Several genes and pathways related to cell adhesion molecules and immunity related cell surface receptors were influenced by conventional-dose 17β-estradiol/NETA. SN - 1879-2472 UR - https://www.unboundmedicine.com/medline/citation/22217510/A_microarray_study_on_the_effect_of_four_hormone_therapy_regimens_on_gene_transcription_in_whole_blood_from_healthy_postmenopausal_women_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0049-3848(11)00659-1 DB - PRIME DP - Unbound Medicine ER -