Journal
SEMINARS IN REPRODUCTIVE MEDICINE
Volume 28, Issue 1, Pages 27-35Publisher
THIEME MEDICAL PUBL INC
DOI: 10.1055/s-0029-1242990
Keywords
Progesterone receptor; progesterone resistance; uterus
Categories
Funding
- NIH [R01HD042311, U54HD0077495, R01CA77530, R01HD057873]
- Susan G. Komen Award [BCTR0503763]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [R01HD057873, R01HD042311, R03HD077495, U54HD007495] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [R01CA077530] Funding Source: NIH RePORTER
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Healthy uterine function depends on the balanced interaction of the ovarian steroids estrogen and progesterone (P4) signaling through their respective receptors. The expression of each receptor is regulated by the other through crucial cross talk between the epithelial and stromal compartments. Ablation of the progesterone receptor ( PR) results in complete infertility in mice, and evidence increasingly demonstrates that the PR is a major mediator of epithelial-stromal cross talk and events leading to the disruption of this communication can lead to P4 resistance in the uterus. This resistance, through impaired P4 signaling, can be at the level of the PR itself, coregulators, and downstream effectors. The mechanisms underlying P4 resistance is of critical importance in women's health because this defect is seen in a wide variety of diseases including infertility, endometriosis, endometrial carcinoma, polycystic ovarian syndrome, and leiomyomas. By using mouse models of PR signaling, many of these mechanisms are beginning to be elucidated and aid in the development of effective therapies for treatment of uterine diseases.
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