Abstract
BackgroundUterine Fibroids (UFs) growth is ovarian steroid-dependent. Previous studies have shown that estrogen and progesterone play an important role in UF development. However, the mechanism underlying progesterone induced UF pathogenesis is largely unknown. In this study, we determined the expression of progesterone receptor and compared the expression level of progesterone-regulated genes (PRGs) in human myometrial cells from normal uteri (MyoN) versus uteri with UFs (MyoF) in response to progesterone.MethodsPrimary human myometrial cells were isolated from premenopausal patients with structurally normal uteri (PrMyoN). Primary human myometrial cells were also isolated from uterus with UFs (PrMyoF). Isolated tissues were excised at least 2 cm from the closest UFs lesion(s). Progesterone receptor (PR) expression was assessed using Western blot (WB). Expression levels of 15 PRGs were measured by qRT-PCR in PrMyoN and PrMyoF cells in the presence or absence of progesterone.ResultsWB analysis revealed higher expression levels of PR in PrMyoF cells as compared to PrMyoN cells. Furthermore, we compared the expression patterns of 15 UF-related PRGs in PrMyoN and PrMyoF primary cells in response to progesterone hormone treatment. Our studies demonstrated that five PRGs including Bcl2, FOXO1A, SCGB2A2, CYP26a1 and MMP11 exhibited significant progesterone-hyper-responsiveness in human PrMyoF cells as compared to PrMyoN cells (P < 0.05). Another seven PRGs, including CIDEC, CANP6, ADHL5, ALDHA1, MT1E, KIK6, HHI showed gain in repression in response to progesterone treatment (P > 0.05). Importantly, these genes play crucial roles in cell proliferation, apoptosis, cell cycle, tissue remodeling and tumorigenesis in the development of UFs.ConclusionThese data support the idea that progesterone acts as contributing mechanism in the origin of UFs. Identification and analysis of these PRGs will help to further understand the role of progesterone in UF development.
Highlights
Uterine Fibroids (UFs) growth is ovarian steroid-dependent
This study showed that P4 receptor mRNA is highly expressed in UF cells as compared the cells from adjacent myometrium
We demonstrated that the expression of Progesterone receptor (PR) was higher in PrMyoF as compared to Primary human myometrial cells from normal uterus (PrMyoN) cells
Summary
Uterine Fibroids (UFs) growth is ovarian steroid-dependent. Previous studies have shown that estrogen and progesterone play an important role in UF development. Uterine fibroids (UFs) are smooth muscle cell tumors originating from the myometrium. Tumors occur in 70– 80% of women overall and are clinically manifested in 25–50% by 50 years of age [1]. A number of antiprogestin drugs and SPRM (selective progesterone receptor modulator) have been developed and tested in clinical trials for the treatment of UFs, including Mifepristone, Asoprisnil and Ulipristal acetate. These studies provide strong evidence for the mitogenic effect of progesterone on UF pathogenesis [9,10,11]
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