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Expression of Steroid Receptor Coactivators in Cultured Cells From Paired Myometrial and Fibroid Tissues

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Abstract

Objectives

Fibroid tumor growth in the myometrium appears to be regulated by estrogens but the role of estrogen receptor (ER) coregulators, such as the steroid receptor coactivator (SRC) family members, in fibroid growth is currently unknown. The aims of this study were to compare the expression of the SRC-1, SRC-2, and SRC-3 coactivators between fibroids and normal myometrium in pure populations of cultured smooth muscle cells (SMC) and microvascular endothelial cells (MEC), and also between both cell types, and to identify any relationship between the SRC expression profiles and the known ER status of the SMC and MEC samples examined in this study.

Methods

Reverse transcriptase—polymerase chain reaction (RT-PCR) coupled with Southern blot analysis was used to derive a semiquantitative estimate of the relative levels of SRC-1, SRC-2, and SRC-3 expression in pure populations of SMC (>98% α-smooth muscle actin [SMA]+) and MEC (>99% CD31+) isolated and cultured from eight samples of paired human myometrial and fibroid tissue.

Results

The mean levels of SRC-1, SRC-2, and SRC-3 were each similar in normal myometrium compared to fibroids for SMC and also for MEC. However, SRC-1, SRC-2, and SRC-3 levels were each significantly higher in SMC compared to MEC from both myometrial and fibroid samples, although for SRC-3 there was a trend for higher levels in myometrial samples that did not reach significance. While all SMC samples expressed ERa and high coactivator levels, there does not appear to be a relationship between coactivator expression levels and the presence or absence of ERa in MEC samples.

Conclusion

Coactivators may be more important in ERa-mediated growth of SMC than for MEC. Although the SRC family members are likely to play a role in the response of fibroid SMC to estrogen, via ERa, changes in their levels do not appear to contribute to the increased sensitivity of fibroid SMC to estrogen.

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Authors and Affiliations

  1. Prince Henry’s Institute of Medical Research and Monash University Department of Medicine, Australia

    Sonay Hussein-Fikret BSc (Hons), Peter J. Fuller MD, PhD & Caroline E. Gargett PhD

  2. Department of Obstetrics and Gynaecology, Monash University, Centre for Women’s Health Researc0h, 246 Clayton Rd, Clayton, Victoria, 3168, Australia

    Sonay Hussein-Fikret BSc (Hons), Peter J. Fuller MD, PhD & Caroline E. Gargett PhD

Authors
  1. Sonay Hussein-Fikret BSc (Hons)
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  2. Peter J. Fuller MD, PhD
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  3. Caroline E. Gargett PhD
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Corresponding author

Correspondence to Caroline E. Gargett PhD.

Additional information

Supported by the National Australia Bank Ovarian Cancer Research Foundation PhD Scholarship Grant (S.H-F.), the National Health and Medical Research Council of Australia Senior Principal Research Fellowship (P.J.F.), and Grants No. 284344 and 124331, and the Monash University Early Career Researcher Grant (C.E.G.).

The authors thank Marina Zaitseva and Kris Bucak for technical assistance; Drs Mark Lawrence, Peter Lutjen, and Beverley Vollenhoven at Monash Medical Centre for provision of hysterectomy tissue; Nancy Taylor for collection of tissue; and Mai Forsyth and the Australian Red Cross Service, Melbourne, for provision of male human serum.

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Hussein-Fikret, S., Fuller, P.J. & Gargett, C.E. Expression of Steroid Receptor Coactivators in Cultured Cells From Paired Myometrial and Fibroid Tissues. Reprod. Sci. 12, 445–451 (2005). https://doi.org/10.1016/j.jsgi.2005.04.008

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