ANATOMY OF THE HUMAN OVARIAN INSULIN-LIKE GROWTH-FACTOR SYSTEM

In situ hybridization was used to map insulin-like growth factor (IGF) system gene expression in ovaries from an anencephalic infant and several young women. Growing oocytes in infant and mature ovaries expressed transcripts for IGF-I and IGF-II, respectively, and all oocytes expressed abundant IGF-I receptor transcripts, raising the possibility of autocrine IGF function in oocyte maturation. IGF-I mRNA was not detected in the mature ovary, but IGF-II mRNA was localized in follicular blood vessels and in granulosa cells (GC) and was especially abundant in the GC of atretic as opposed to young follicles. IGF-I receptor mRNA was abundant in GC of antral and atretic follicles, and was expressed at low levels in the thecal interstitial compartments. IGF-binding protein (IGFBP) 1 mRNA was not detected, but IGFBPs 2-5 mRNAs each demonstrated a unique ovarian distribution. IGFBP2 mRNA was abundant in GC and thecal cells at all stages of development. IGFBP3 mRNA was detected only in the endothelium of ovarian blood vessels. IGFBP4 mRNA was also localized in endothelium, but in addition was present in stromal connective tissue and in GC of the one Graafian follicle detected in this study, but not consistently in atretic follicles. IGFBP5 mRNA was expressed by luminal or cumulus GC in virtually all follicles and was highly abundant in stromal interstitial cells of the mature ovary. Insofar as our limited sample allows developmental analysis, gene expression for the IGF-I receptor and IGF-II in GC and for IGFBP5 in interstitial cells appeared to be developmentally or hormonally regulated, as their mRNAs were significantly more abundant in mature ovaries than in ovaries from an anencephalic infant. GC gene expression for IGFBP2 and IGFBP5, in contrast, appears to be constitutive. In summary, the intensity, compartmentalization, and developmental regulation of IGF system gene expression in the human ovary support the view that IGFs play an important and complex role in ovarian physiology. The striking evidence of IGF ligand and receptor gene expression in human oocytes suggests that IGFs have a role in growth from the earliest moments in development.