INSULIN-LIKE GROWTH-FACTOR SYSTEM GENE-EXPRESSION IN HUMAN ENDOMETRIUM DURING THE MENSTRUAL-CYCLE

To study the cellular patterns of gene expression of the insulin-like growth factor (IGF) system in human endometrium during the menstrual c ycle, we used in situ hybridization histochemistry to localize messeng er ribonucleic acids (mRNAs) encoding IGF-I and -II, their receptors, and their binding proteins (IGFBPs) in fresh-frozen endometrial tissue obtained from cycling women. IGF-I and IGF-II mRNAs are both expresse d diffusely throughout endometrial stroma and are not detected in endo metrial epithelium. Endometrial IGF-I mRNA is significantly more abund ant during the proliferative than the secretory phase of the menstrual cycle, whereas the reverse is true for IGF-II. Type I and type II IGF receptor mRNAs are both present in endometrial stroma, but are relati vely more abundant in endometrial epithelium, and neither shows distin ctive cyclic changes. IGFBP-2, -4, -5, and -6 mRNAs demonstrate a diff use stromal pattern of expression, whereas IGFBP-1 and -3 are more foc ally concentrated in selected subpopulations of endometrial cells. IGF BP-1 mRNA is not detected in proliferative endometrium and demonstrate s a very heterogeneous pattern of expression in secretory endometrium, where it is intensely abundant in a patchy distribution of stromal an d epithelial cells. IGFBP-3 mRNA is primarily concentrated in endometr ial capillaries and is increased in the secretory phase, largely due t o the intense vascularization of endometrial glands during this phase. IGFBP-5 mRNA is more abundant in the proliferative phase, but all oth er IGFBP mRNAs are relatively increased in the secretory phase of the menstrual cycle. These findings support the view that the IGF system p lays a fundamental role in endometrial biology, acting via autocrine a nd/or paracrine mechanisms, with IGF-I and IGPBP-5 being dominant in t he proliferative phase, and IGF-II and the other IGFBPs predominant in the secretory phase of the menstrual cycle.