EXPRESSION OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF-II AND THEIGF-I, IGF-II AND INSULIN-RECEPTOR GENES AND LOCALIZATION OF THE GENE-PRODUCTS IN THE HUMAN OVARY

We examined the expression of the genes encoding the insulin-like grow th factors (IGFs) and their receptors (r) and the localization of thei r gene products in specific cellular compartments of the human ovary. mRNA was localized by in situ hybridization with specific human S-35-l abeled antisense RNA probes, and protein was detected by immunocytoche mistry with specific antisera. We studied 34 follicles (10 ovaries), w hich included both dominant and small antral follicles. In dominant fo llicles, no IGF-I mRNA was seen in either thecal or granulosa cells (G C), but IGF-Ir mRNA was expressed in GC. In contrast, abundant IGF-II mRNA was found exclusively in GC, whereas the IGF-IIr gene was express ed in both thecal cells and GC. Insulin receptor mRNA was widely distr ibuted and expressed in all cell types, including stromal cells. Small antral follicles contained both IGF-I and IGF-II mRNA, which was rest ricted to thecal cells. Although IGF-Ir message was detected only in G C, IGF-IIr mRNA was expressed in both granulosa and thecal cells. As i n dominant follicles, insulin receptor mRNA was found in thecal, granu losa, and stromal cells. No IGF-I immunoreactivity was seen in either dominant or small antral follicles; however, immunostaining for the ot her gene products demonstrated that each of these proteins colocalized with its corresponding mRNA. Thus, the relative distribution of ligan d and receptor transcripts and protein in cellular compartments of the human ovary observed in this study supports the presence of an intrao varian IGF system and suggests that both autocrine and paracrine mecha nisms of IGF action occur between GC and thecal cells. We conclude tha t 1) IGF-II, rather than IGF-I, is the principal IGF in human ovarian follicles, being synthesized in thecal cells in small antral follicles and in GC in dominant follicles; 2) in small antral follicles, IGF-II acts in an autocrine fashion in thecal cells and in a paracrine fashi on in GC; 3) in dominant follicles, granulosa-derived IGF-II acts in a n autocrine manner in GC; and 4) the presence of transcripts and prote ins corresponding to the IGF and insulin receptors in cellular compart ments of human ovaries may also provide target sites for the action of circulating ligands with a potential extraovarian role in the regulat ion of folliculogenesis.