Fulvestant as an anti-steroid agent, modifies growth-related gene expression of ovarian cells via selective estrogen receptor down regulator (serd) effects.

Majid Banimohammad,1,* Abbas majdi seghinsara ,2 Danial gholamin,3 Hamidreza pazoki-toroudi,4

1. Medical Student, Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran and Young Researchers and Elite Club, Ardabil Branch, Islamic Azad University, Ardabil, Iran.
2. Department of Anatomical Science, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran.
3. School of Pharmacy, Ardabil University of Medical Science, Ardabil, Iran.
4. Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Abstract

Introduction

Fulvestrant as a drug with down-regulating effect on estrogen receptors, is used in treatment of hormone receptor-positive metastatic breast cancer in post-menopausal woman. fulvestrant also is an estrogen antagonist that this feature prevents from breast cancer metastases. in the other hand, estrogen as one of the important female hormones, has decisive association in menstrual cycle which effect on intracellular pathways of granulosa cells in adult mammals by expression of some gene such as gdf9. by investigating the effects of this drug on folliculogenesis and differentiation of ovarian cells, it could clarify the use of fulvestrant in pre-menopausal period even when it is associated by poor ovarian reserve (por)

Methods

In present study, samples were collected from the surface epithelium of the ovary from 8 women over 37 years. samples were divided into 2 groups (control group with dmem/f12 ham culture medium; and fulv group with fulvestrant (100 nm/ml) + estradiol (1ng/ml), added to culture medium). then the samples were cultured in medium for 3 weeks. finally, gdf9 expression in cultured cells were measured by rt-pcr and morphology of cells were studied by microscope.

Results

In the control group the folliculogenesis and gdf9 gene expression were significantly different from fulv group that treated with fulvestrant. estradiol caused similarity between cultured cells of control group and real follicle morphology. in the fulv group the gdf 9 gene expression decreased significantly (p<0.001) and the cell growth related to folliculogenesis was not in biological situation. the granulosa cells and oocytes have very small size and their shape were different from normal follicular and oocyte cells.

Conclusion

This study demonstrated that the fulvestrant is an antiestrogen agent that prevent estrogen effects via competitive antagonistic effects on estrogen receptors. also fulvestrant could affects estrogen receptors in higher doses whereas other estrogen antagonists have estrogenic effects in higher doses. so it could be concluded that this drug even inhibits differentiation of non-specific cells to follicular cells. finally, fulvestrant could have negative effect in ovarian reserve.

Keywords

Fulvestant, folliculogenesis, ovary, ovarian reserve