Progesterone-Growth Factor Interactions in Uterine Stromal Cells: A NEW MODEL FOR STUDYING PROGESTERONE(3)

In: Progesterone

8 Feb 2013

A major concern regarding the usefulness of this model is the apparent lack of estrogen-dependent proliferation. While a nidatory amount of estradiol is required to initiate stromal cell proliferation in vivo, no direct effect of estrogen on cell cycle progression in uterine stromal cells has been demonstrated. Therefore, our interpretation of the existing evidence is that estrogen functions in two important aspects of stromal cell proliferation (see Fig. 5). First, estrogen may be necessary in intact animals to stimulate the synthesis of progesterone receptor rather than to direct cell cycle progression. Consistent with this interpretation, estrogen induces transcription of the progesterone receptor via an intragenic response element, and Kraus and Katzenellenbogen showed that estrogen is required for progestin action in the ovariectomized rat uterus because the progesterone receptor content is low. We have clearly demonstrated that proliferating uterine stromal cells express both the A and B forms of the progesterone receptor. Moreover, addition of progesterone receptor antagonist RU-486 to stromal cell cultures containing bFGF and progesterone significantly inhibited proliferation. Since the serum-free medium used in our studies is phenol red free, it is not clear how progesterone receptor expression is regulated in these cells. The simplest interpretation is that increased expression of progesterone receptor occurs during the prior passage of these cells in medium containing 10%serum. Alternatively, progesterone receptor synthesis may be the result of a coupling between the estrogen receptor to an insulin-dependent mechanism as shown for neuroblastoma cells in culture, since insulin is a component in the serum-free medium used in our cell proliferation studies. Addition of estradiol to stromal cell cultures containing progesterone and bFGF enhanced the proliferative response as compared to that with progesterone and bFGF without estradiol, but the difference was not significant. We are currently investigating whether stromal cells in culture express estrogen receptors. buy ortho tri-cyclen online
Fig5Progesterone-Growth Factor
FIG. 5. Proposed model for progesterone-dependent stromal cell proliferation showing potential control points for cell cycle progression. Cells are driven into S and M phases by the formation of cyclin-cdk complexes. Progesterone may stimulate the synthesis of cyclins in G1 and G2 phases of the cell cycle. Activation of the complex requires kinase binding to cyclin, phosphorylation, and dephosphorylation. Estrogen may be necessary for the synthesis of growth factors and progesterone receptor in vivo, but its action is not required for stromal cell proliferation in culture. See text for details.


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