Estrogen receptor alpha is essential for the proliferation of prostatic smooth muscle cells stimulated by 17β‐estradiol and insulin‐like growth factor 1

Abstract

Estradiol (E₂) and its receptor estrogen receptor alpha (ERα) are implicated in the pathology of stromal-predominant benign prostatic hyperplasia (BPH). Insulin-like growth factor 1(IGF1) is produced primarily by stromal cells in the prostate. Recent study showed that E₂-mediated regulation of IGF1 in mouse uterus requires the DNA binding ability of ERα. However, the crosstalk between ERα and IGF1 in the prostate has not been addressed yet. Therefore, in this study we employed mouse prostatic smooth muscle cells (PSMCs) as a model to demonstrate that E₂ stimulated the proliferation of PSMCs and up-regulated the expression of IGF1 and its receptor IGF1R as well as cyclin D1 in PSMCs, all of which could be inhibited by shRNA-mediated knockdown of ERα. Furthermore, we found that exogenous IGF1 could not promote cell proliferation and cyclin D1 expression in PSMCs subjected to shRNA-mediated knockdown of ERα. Interestingly, blockage of IGF1R by antibody could inhibit E₂-stimulated PSMCs proliferation. Altogether our present study provides the first line of evidence that there is crosstalk between ERα and IGF1 signaling in PSMCs proliferation in which ERα up-regulates the expression of IGF1 and IGF1R, and IGF1 signaling is indispensable to mediate downstream effects of E₂ and ERα.

Cooperative effects of EGF, FGF, and TGF-β1 in prostate stromal cells are different from responses to single growth factors

“…In fact, growth factors induce a periodic increase of cyclin D1 abundance by several mechanisms, which peaks during G1 [31,34]. Consequently, cyclin D1 levels are frequently used as a marker for proliferation, including investigations performed in prostate smooth muscle cells [35,36].…”

Distinct Function of Estrogen Receptor α in Smooth Muscle and Fibroblast Cells in Prostate Development

“…3). Previous studies have shown that E 2 can up-regulate IGF-I in smooth muscle cells and that this upregulation can increase these cells' proliferation (41). In addition to IGF, we have also observed that ER␣ can regulate EGF in other cell lines (Yeh, S., unpublished data).…”

Seasonal variation in estrogen receptor ERα, but not ERβ, androgen receptor and aromatase, in the efferent ductules and epididymis of the big fruit-eating bat Artibeus lituratus

“…These data suggest that besides contractibility, ERa may be involved in other epididymal functions. Indeed a recent study revealed that ERa is essential for proliferation of smooth muscle cells in the rat prostate [56]. Additionally, there is a growing body of evidence that factors arising from the interstitium may be important in stimulating epithelial cells by a paracrine action in diverse organs [49,56].…”