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17β-Estradiol Induces Overproliferation in Adenomyotic Human Uterine Smooth Muscle Cells of the Junctional Zone Through Hyperactivation of the Estrogen Receptor-Enhanced RhoA/ROCK Signaling Pathway

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Abstract

Adenomyosis (ADS) is a common estrogen-dependent gynecological disease with unknown etiology. Recent models favor abnormal thickening of the junctional zone (JZ) may be the causative factor in the development of ADS. RhoA, a small guanosine triphosphatase which controls multiple cellular processes, is involved in the control of cell proliferation. Here we demonstrate that treatment of human uterine smooth muscle cells (SMCs) of the JZ with 17β-estradiol (E2) increased expression of RhoA and its downstream effectors (-associated coiled coil containing protein kinase [ROCK] 1 and ROCK2). Compared with non-ADS cells, RhoA, ROCK1, and ROCK2 were overexpressed and hyperactivated in ADS cells. These effects were suppressed in the presence of ICI 182,780, supporting an estrogen receptor (ER)-dependent mechanism. Hyperactivation of ER-enhanced RhoA/ROCK signaling was associated with overproliferation in ADS human uterine SMCs of the JZ. Moreover, E2-induced overproliferation was accompanied by downregulation of cyclin-dependent kinases inhibitors (CKIs; p21Waf1/Cip1 and p27Kip1) and upregulation of cyclin-dependent kinases (CDKs) and cyclins (cyclin D1, cyclin E1, CDK2, CDK4, and CDK6).

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Authors and Affiliations

  1. Department of Gynecology, Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Qi Helou Street No. 17, Dong Cheng District, Beijing, China

    Fu-Qing Sun MD, Hua Duan MD, PhD, Sha Wang MD & Jin-Jiao Li MD

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  1. Fu-Qing Sun MD
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  2. Hua Duan MD, PhD
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  3. Sha Wang MD
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  4. Jin-Jiao Li MD
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Correspondence to Hua Duan MD, PhD.

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Sun, FQ., Duan, H., Wang, S. et al. 17β-Estradiol Induces Overproliferation in Adenomyotic Human Uterine Smooth Muscle Cells of the Junctional Zone Through Hyperactivation of the Estrogen Receptor-Enhanced RhoA/ROCK Signaling Pathway. Reprod. Sci. 22, 1436–1444 (2015). https://doi.org/10.1177/1933719115584447

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