Progesterone-Growth Factor Interactions in Uterine Stromal Cells: CELL CYCLE REGULATION(2)

In: Progesterone

5 Feb 2013

CELL CYCLE REGULATION(2)

Since hormones may also act directly and stimulate expression of genes required for cell cycle transit, identifying hormone-dependent versus growth factor-mediated changes in cell cycle progression is essential. For example, estrogen and progesterone increase c-Jun and c-fos mRNAs in the ovariectomized rat uterus; but it is not clear whether the resulting proteins regulate cell cycle genes, the synthesis of growth factors involved in cell cycle progression, or perhaps both. The difficulties in resolving these issues using an in vivo model are apparent because expression of these protooncogenes does not correlate strictly with cell proliferation in the uterus. buy diabetes drugs

The challenge of defining the molecular mechanisms of hormone action on the endometrium are further suggested from the recent studies of Cooke and colleagues; and see minireview in this issue ). The reconstitution experiments using stromal and epithelial cells from estrogen receptor-deficient mice clearly show that epithelial cell proliferation in the mouse is mediated via estrogen receptor action from the stroma. Similarly, analysis of progesterone receptor distribution in a variety of mammalian species indicates an absence of progesterone receptor in epithelial cells at the time of implantation. Thus, epithelial cell differentiation in response to progesterone may be mediated, in part, through stromal cell progesterone receptors. Formal proof for this concept is required, but together these findings reemphasize the importance of the stroma as an epithelial cell modulator in uterine development and the sensitization of the endometrium for implantation. Importantly, these newly emerging concepts about the mechanisms involved in hormonal control of cell proliferation are derived from different experimental approaches, indicating the importance of multifaceted research strategies to study complex biological problems.


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