A microarray study on the effect of four hormone therapy regimens on gene transcription in whole blood from healthy postmenopausal women

Dahm, Anders E.A.; Eilertsen, Anette L.; Goeman, Jelle; Olstad, Ole Kristoffer; Øvstebø, Reidun; Kierulf, Peter; Mowinckel, Marie-Christine; Skretting, Grethe; Sandset, Per Morten

doi:10.1016/j.thromres.2011.12.009

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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

Anders E.A. Dahm
- Department of Haematology, Oslo University Hospital, Oslo, Norway
- Corresponding author at: Oslo University Hospital Rikshospitalet, Department of Haematology, BOX 4950 Nydalen, N-0424 Oslo, Norway. Tel.: +47 93059809; fax: +47 22 11 90 40.
- AEAD and ALE contributed equally to the manuscript.
Anette L. Eilertsen
- Department of Haematology, Oslo University Hospital, Oslo, Norway
- AEAD and ALE contributed equally to the manuscript.
Jelle Goeman
- Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands
Ole Kristoffer Olstad
- Department of Clinical Biochemistry, Oslo University Hospital, Oslo, Norway
Reidun Øvstebø
- Department of Clinical Biochemistry, Oslo University Hospital, Oslo, Norway
Peter Kierulf
- Department of Clinical Biochemistry, Oslo University Hospital, Oslo, Norway
Marie-Christine Mowinckel
- Department of Haematology, Oslo University Hospital, Oslo, Norway
Grethe Skretting
- Department of Haematology, Oslo University Hospital, Oslo, Norway
Per Morten Sandset
- Department of Haematology, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Received 27 September 2011; received in revised form 9 November 2011; accepted 2 December 2011. published online 04 January 2012.
Corrected Proof

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.

Keywords: Gene expression, Microarray, Postmenoupausal hormone therapy