Highlights From the Society for Gynecologic Investigation 51st Annual Meeting

John F. Randolph, Jr, MD


April 18, 2003

In This Article

Progesterone and Estrogen Regulate Each Other Through Receptor Modulation

Kathryn Horwitz of the University of Colorado School of Medicine, Denver, gave the C.D. Christian Distinguished Lecture highlighting her extensive work on the actions of estrogens and progestins in breast cancer and endometrium. She emphasized the concept that progesterone regulates the action of estrogen through modulation of estrogen receptors (ER), and that estrogens similarly regulate the action of progesterone through modulation of the 2PRs. This leads to different effects of estrogens and progesterone in different tissues. She reviewed a number of clinical studies suggesting that, although progesterone decreases the cancer-promoting action of estrogen in the endometrium and ovary, it appears to increase the cancer-promoting action of estrogen in the breast.

Of the 2 PRs, PR-B is 10 times more active than PR-A in response to progesterone. The relative proportion of the 2 receptors also varies in different tissues, and in normal vs neoplastic tissues, raising the possibility of specific selective PR modulators, or SPRMs, to treat such disorders as endometriosis and breast cancer. The relative proportion of PR-A to PR-B in breast tumors seems to predict response to hormonal therapy and long-term survival and may prove to be an indicator of the most appropriate therapy to use.

Comment: This work highlights the improving understanding of the complexity and plasticity of the sex steroid/receptor system in 2 classical target tissues, the breast and the endometrium. Although these findings have made clinical care temporarily more confusing, they offer better explanations for contradictory findings from clinical studies. They also offer the prospect of very targeted therapy tailored to the genetic and environmental particulars for individual patients. One can imagine families of selective estrogen, progestin, and androgen modulators (SERMs, SPRMs, and SARMs) used in various combinations much the same that antihypertensives are used today.


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