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The effect of short-term oral contraceptive use on the expression of syndecan-1, syndecan-4, decorin and the androgen receptor in breast tissue from women of fertile age
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
Institutionen för Kvinnors och Barns hälsa, Karolinska Institutet, Solna.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
Institutionen för Kvinnors och Barns hälsa, Karolinska Institutet, Solna.
2011 (English)In: The Breast Journal, ISSN 1075-122X, E-ISSN 1524-4741Article in journal (Other academic) Submitted
Abstract [en]

Background

In non-cancerous breast tissue from premenopausal women, we examined gene expression and protein levels of the androgen receptor and the proteoglycans decorin, syndecan-1 and syndecan-4, before and after use of oral contraceptives (OC).

Material and Methods

Premenopausal women (n = 20) undergoing breast reduction plastic surgery, received two months use of  combined oral contraceptive with ethinylestradiol 30μg and levonorgestrel 150μg. Breast tissue was sampled at mammography (needle biopsy) two months before and at the operation. We analysed immunohistochemistry (n = 20) and real-time RT-PCR (n = 10).

Results

After two months of OC use, we found a significant decrease in the protein levels of syndecan-4 (p = 0.003), the androgen receptor (p = 0.002) and decorin (p = 0.018), but not of syndecan-1 protein, compared to expression during the follicular phase in the normal menstrual cycle before OC use.  Real- time RT-PCR indicated a significant decrease in gene expression for decorin (p = 0.002).  

Conclusions

In pre-menopausal women, short-term OC use yielded lower protein levels of syndecan-4, the androgen receptor and decorin, and lower gene expression for decorin, compared to that during the follicular phase of the menstrual cycle before OC use.

Place, publisher, year, edition, pages
2011.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-147741OAI: oai:DiVA.org:uu-147741DiVA: diva2:400829
Note

pubkoll2017

Available from: 2011-02-28 Created: 2011-02-28 Last updated: 2017-05-15Bibliographically approved
In thesis
1. Effects of Endogenous and Exogenous Hormones on the Female Breast: With Special Reference to the Expression of Proteoglycans
Open this publication in new window or tab >>Effects of Endogenous and Exogenous Hormones on the Female Breast: With Special Reference to the Expression of Proteoglycans
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis aims to study the effects of endogenous and exogenous hormones and mammographic breast density (BD) on cellular markers in non-cancerous female breast tissue. Women on the waiting list for breast reduction plastic surgery were recruited (n = 79), and randomized to 2 months of hormone therapy or no therapy before surgery. The women had a mammogram and a needle biopsy 2 months before surgery and tissue samples were obtained at the operation.

In premenopausal women, estrogen receptor (ER)α levels were associated with age (p = 0.0002), were similar in the follicular and luteal phases of the menstrual cycle and were higher in parous than in nulliparous women (p = 0.009). Current smokers had lower PR levels than non-smokers (p = 0.019). Women on oral contraception had lower ERα (p = 0.048) and PR (p = 0.007) levels than women in the follicular phase. The ERα levels did not differ significantly between postmenopausal estrogen and estrogen-progestogen users, but PR levels were lower among estrogen-progestogen users (p = 0.03).

We found lower expression of the genes for decorin and syndecans 1 and 4 in the luteal phase than in the follicular phase, among parous women. Protein levels of the androgen receptor, syndecan-4 and decorin was lower in premenopausal women who were using oral contraceptives (OC) than in those in the follicular phase (p = 0.002 - 0.02), whereas no significant differences between OC use and the luteal phase were found.

In premenopausal women, BD was negatively associated with age and body mass index but was similar for the menstrual phases. Breast density was associated with genetic expression of the androgen receptor and remained significant after adjustment for age (rs = 0.56; p = 0.04). After adjustement for age, breast density was also marginally associated with expression of the caspase 3 gene (0.55; 0.053). However, protein levels of caspase 3 was negatively associated (-0.61; 0.03).

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 76 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 651
Keyword
breast tissue, proteoglycans, mammographic density, oral contraceptives, androgen receptor, proliferation, apoptosis, extracellular matrix, premenopausal
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-147793 (URN)978-91-554-8018-9 (ISBN)
Public defence
2011-04-14, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2011-03-23 Created: 2011-02-28 Last updated: 2011-05-04Bibliographically approved

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Hallberg, Gunilla

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