Medicine of the Future in America

Hormonal Control of the Cell Cycle in Ovarian Cells: MECHANISMS OF CELL CYCLE CONTROL(3)

Additionally, the cAMP/protein kinase A cascade controls the exit from mitosis by regulating the degradation of cyclin B. Thus, not only can the presence or level of hormone, i.e., FSH versus LH, alter the amount of a regulatory molecule; it can also exert effects at multiple points within the cell cycle machinery, at G1-S and M-G1 (Fig. 7).

Estrogens are known to be potent mitogens and are often associated with cancer. Indeed, most studies that have been designed to determine the mechanism by which estrogens, principally estradiol, regulate proliferation have been performed in breast cancer cell lines, in which the cell cycle machinery and the signals impinging on the cell cycle may be abnormal. In these cell lines, estradiol is able to increase the activity of cdk4 and cdk2 by inducing expression of cyclin D1 as well as by decreasing the levels of cdk inhibitors. Similar mechanisms have also been observed in the uterus, where estradiol induces cyclins D1, D3, E, and A. We have shown that estradiol induces the expression of cyclin D2 and cyclin E in granulosa cells, concurrent with a reduction in levels of p27. Simultaneous down-regulation of a cdk inhibitor and induction of cyclins may account for the greater mitogenicity of estradiol compared to FSH in these cells. Studies have also shown that cyclin D1 can directly bind the estrogen receptor and enhance transcription of specific genes. It would be interesting to determine whether such a mechanism occurs in granulosa cells, which selectively express the beta subtype of the estrogen receptor (ERp; ) and in which estradiol induces cyclin D2. buy ortho tri-cyclen

Lastly, there are many additional hormones that act in the ovary to affect cellular proliferation and differentiation. For instance, activin, which is produced at high levels in preovulatory granulosa cells, has been shown to stimulate granulosa cell DNA synthesis. Therefore, it is possible that activin along with estradiol and FSH regulates cyclin D2.

This entry was posted in Ovarian Cells and tagged Cell Cycle, Differentiation, Hormonal Control, Ovarian Cells.
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