Expression of insulin-like growth factor-I (IGF-I) and IGF-II and the IGF-I, IGF-II, and insulin receptor genes and localization of the gene products in the human ovary.

Abstract

We examined the expression of the genes encoding the insulin-like growth factors (IGFs) and their receptors (r) and the localization of their gene products in specific cellular compartments of the human ovary. mRNA was localized by in situ hybridization with specific human 35S-labeled antisense RNA probes, and protein was detected by immunocytochemistry with specific antisera. We studied 34 follicles (10 ovaries), which included both dominant and small antral follicles. In dominant follicles, no IGF-I mRNA was seen in either thecal or granulosa cells (GC), 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 expressed in both thecal cells and GC. Insulin receptor mRNA was widely distributed and expressed in all cell types, including stromal cells. Small antral follicles contained both IGF-I and IGF-II mRNA, which was restricted to thecal cells. Although IGF-Ir message was detected only in GC, IGF-IIr mRNA was expressed in both granulosa and thecal cells. As in dominant follicles, insulin receptor mRNA was found in thecal, granulosa, and stromal cells. No IGF-I immunoreactivity was seen in either dominant or small antral follicles; however, immunostaining for the other gene products demonstrated that each of these proteins colocalized with its corresponding mRNA. Thus, the relative distribution of ligand and receptor transcripts and protein in cellular compartments of the human ovary observed in this study supports the presence of an intraovarian IGF system and suggests that both autocrine and paracrine mechanisms of IGF action occur between GC and thecal cells. We conclude that 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 fashion in GC; 3) in dominant follicles, granulosa-derived IGF-II acts in an autocrine manner in GC; and 4) the presence of transcripts and proteins corresponding to the IGF and insulin receptors in cellular compartments of human ovaries may also provide target sites for the action of circulating ligands with a potential extraovarian role in the regulation of folliculogenesis.

Insulin-like Growth Factor Family in Graafian Follicle Development and Function

“…IGF-II mRNA is expressed in theca and bolic effects mediated upon binding to specific high-affinity perifollicular vessels of all follicles. [3][4][5] androgen from theca is used as substrate for FSH-and IGFof IGF action, IGFBT s are effectiv~ely antigonladotropins. is a potent inhibitor of FSH (and IGF-II) stimulated stimulated aroniatase for the production of E,.…”

GWAS meta-analysis highlights the hypothalamic-pituitary-gonadal axis (HPG axis) in the genetic regulation of menstrual cycle length

“…Further experimental validation will be necessary to fully unravel the mechanism of these non-coding associations. has been proposed to be an important local regulator of folliculogenesis [25], as it stimulates estrogen production [26] and modulates the action of FSH and LH, whereas IGF2 expression in turn is regulated by FSH [27]. However, to our knowledge no direct link between genetic variation in the INS-IGF2 region and menstrual cycle length had been previously demonstrated.…”

Insuline-Like Growth Factor-2 (IGF2) and Hepatocyte Growth Factor (HGF) Promote Lymphomagenesis in p53-null Mice in Tissue-specific and Estrogen-signaling Dependent Manners

“…IGF2 is the growth hormone specifically for the development of the fetus and ovarian follicle [33][34][35]. IGF2 is also a maternally imprinted gene that is commonly overexpressed in cancer cells through loss of imprinting (LOI) [36].…”