Role of stromal-epithelial interactions in hormonal responses

Cunha, Gerald R.; Cooke, Paul S.; Kurita, Takeshi

doi:10.1679/aohc.67.417

Cited by 273 publications

(222 citation statements)

References 72 publications

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“…Progesterone receptor expression remained high in these areas, however, and both ERa and PR were often highly expressed in the underlying stroma. Recent studies utilizing receptor knockout mouse models have demonstrated that hormone-induced epithelial proliferation can be mediated by stromal receptors in a paracrine manner (Cunha et al, 2004). Similar to previous findings in harbor seals, squamous differentiation was most often noted during late estrus, further suggesting hormone involvement (Bigg and Fisher, 1974).…”

Section: Estrogen and Progesterone Receptor Expressionsupporting

confidence: 73%

The Normal Genital Tract of the Female California Sea Lion (Zalophus californianus): Cyclic Changes in Histomorphology and Hormone Receptor Distribution

Colegrove

Gulland

Naydan

et al. 2009

The Anatomical Record

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Changes in reproductive tract histomorphology, and estrogen (ERa) and progesterone receptor (PR) expression throughout the breeding cycle were evaluated in free-ranging stranded female California sea lions (Zalophus californianus). Hormone receptor expression in the ovaries, uterus, cervix, and vagina was evaluated using an immunohistochemical technique with monoclonal antibodies. During a large portion of the cycle, ovaries contained both a corpora lutea (CL) and follicles in varying stages of development. In the periods of pupping and estrus during June and July, and in the spring morphologic features of the endometrium suggested estrogen influence. There were areas of squamous differentiation in the pseudostratified columnar epithelium of the cervix and vagina in some animals during estrus and in the spring. Estrogen receptor immunohistochemical scores were highest during pupping and estrus and in the spring and lowest during embryonic diapause. Cyclic changes in uterine PR expression throughout the cycle were minimal. Both ERa and PR were expressed in epithelial and stromal cells throughout the cervix and vagina, however, receptor expression was typically higher in the stroma. Stromal cell hormone receptors may play an important role in epithelial responses to circulating sex hormones. The results of this investigation add to the general knowledge of California sea lion reproduction and establish baseline information on reproductive tract hormone receptors that will aid in determining the factors involved in urogenital cancer development in sea lions.

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Section: Estrogen and Progesterone Receptor Expressionsupporting

confidence: 73%

The Normal Genital Tract of the Female California Sea Lion (Zalophus californianus): Cyclic Changes in Histomorphology and Hormone Receptor Distribution

Colegrove

Gulland

Naydan

et al. 2009

The Anatomical Record

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“…Immunohistochemical analysis of PR expression in the Mig-6 d/d mice showed that epithelial PR expression is not altered but that PR expression in the endometrial stroma cells is significantly reduced. P4 attenuates E2 regulation of proliferation and gene expression by regulating the expression of a yet-to-beidentified paracrine signal from the stromal cells to the epithelial cells (41,42). However, the increase in ER␣ target gene expression at 8 weeks of age was not the result of a change in ER␣ or coactivator level (data not shown).…”

Section: Downregulation Of Mig-6 In Human Endometrialmentioning

confidence: 89%

Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease

Jeong

Lee

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

118

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Normal endometrial function requires a balance of progesterone (P4) and estrogen (E2) effects. An imbalance caused by increased E2 action and/or decreased P4 action can result in abnormal endometrial proliferation and, ultimately, endometrial adenocarcinoma, the fourth most common cancer in women. We have identified mitogen-inducible gene 6 (Mig-6) as a downstream target of progesterone receptor (PR) and steroid receptor coactivator (SRC-1) action in the uterus. Here, we demonstrate that absence of Mig-6 in mice results in the inability of P4 to inhibit E2-induced uterine weight gain and E2-responsive target genes expression. At 5 months of age, the absence of Mig-6 results in endometrial hyperplasia. Ovariectomized Mig-6 d/d mice exhibit this hyperplastic phenotype in the presence of E2 and P4 but not without ovarian hormone. Ovariectomized Mig-6 d/d mice treated with E2 developed invasive endometrioid-type endometrial adenocarcinoma. Importantly, the observation that endometrial carcinomas from women have a significant reduction in MIG-6 expression provides compelling support for an important growth regulatory role for Mig-6 in the uterus of both humans and mice. This demonstrates the Mig-6 is a critical regulator of the response of the endometrium to E2 in regulating tissue homeostasis. Since Mig-6 is regulated by both PR and SRC-1, this identifies a PR, SRC-1, Mig-6 regulatory pathway that is critical in the suppression of endometrial cancer.estrogen ͉ endometrial cancer ͉ progesterone ͉ progesterone receptor ͉ SRC-1

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“…In the human or rodent prostate, the prostate gland is composed of not only epithelial cells but also stromal cells, endothelial cells and immune cells [55][56][57][58]. The epithelium requires the support of the stromal cells for epithelial differentiation, proliferation and apoptosis.…”

Section: In Vitro Epithelium-stroma Co-culture Systems and In Vivo Anmentioning

confidence: 99%

The diverse and contrasting effects of using human prostate cancer cell lines to study androgen receptor roles in prostate cancer

Yu¹,

Lai²,

Xia³

et al. 2008

Asian J Androl

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The androgen receptor (AR) plays an important role in the development and progression of prostate cancer (PCa). Androgen deprivation therapy is initially effective in blocking tumor growth, but it eventually leads to the hormonerefractory state. The detailed mechanisms of the conversion from androgen dependence to androgen independence remain unclear. Several PCa cell lines were established to study the role of AR in PCa, but the results were often inconsistent or contrasting in different cell lines, or in the same cell line grown under different conditions. The cellular and molecular alteration of epithelial cells and their microenvironments are complicated, and it is difficult to use a single cell line to address this important issue and also to study the pathophysiological effects of AR. In this paper, we summarize the different effects of AR on multiple cell lines and show the disadvantages of using a single human PCa cell line to study AR effects on PCa. We also discuss the advantages of widely used epithelium-stroma co-culture systems, xenograft mouse models, and genetically engineered PCa mouse models. The combination of in vitro cell line studies and in vivo mouse models might lead to more credible results and better strategies for the study of AR roles in PCa.

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Role of stromal-epithelial interactions in hormonal responses

Abstract: prostate (squamous metaplasia). The mechanistic basis of these stromal-epithelial interactions is poorly understood, but growth factors appear to be mediators of these cell-cell interactions.

Cited by 273 publications

References 72 publications

The Normal Genital Tract of the Female California Sea Lion (Zalophus californianus): Cyclic Changes in Histomorphology and Hormone Receptor Distribution

The Normal Genital Tract of the Female California Sea Lion (Zalophus californianus): Cyclic Changes in Histomorphology and Hormone Receptor Distribution

Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease

The diverse and contrasting effects of using human prostate cancer cell lines to study androgen receptor roles in prostate cancer

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