A series of publications over the past 15 years has established a critical role for local production of IGF-I by E2 in the uterus and for signaling through the IGF-I receptor in stimulating physiological uterine endometrial proliferation during the menstrual cycle. Several key questions raised by these observations and others should provide the impetus for ongoing fundamental research in this area. One problem worth unraveling is defining the molecular mechanisms regulating IGF-I gene expression in the uterus at the level of gene transcription, and possibly RNA stability. Another question concerns assigning specific functions to the different signaling pathways that are activated through the IGF-I receptor in uterine endometrial epithelial and stromal cells. A third area to consider is the role of feedback loops and receptor cross talk in modulating the extent and duration of the biological responses to both E2 and IGF-I in the uterus. The opportunity to answer these and other questions in physiologically relevant terms should have an impact not only on the fundamental biology of the reproductive system but also on a number of serious and common health problems such as endometriosis and endometrial cancer.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism