Role of Insulin-Like Growth Factor-I (IGF-I) and Kit Ligand (KL) in Ovarian Function

Background: The ovarian function is coordinated by many growth factors and hormones responsible for ensuring the success of follicular and oocyte development. To obtain competent oocytes is necessary to have a perfect interaction between follicular somatic cells and the oocyte, which is potentially regulated by paracrine factors produced in the ovary. Among these factors, we highlight the insulin-like growth factor-I (IGF-I) and Kit ligand (KL). This review summarizes the main aspects of molecular structure of IGF-I and KL and their receptors, the mechanisms of action and expression of these substances, as well as their role on ovarian function. Review: The IGF-I is a peptide structurally similar to proinsulin, and is part of IGF-I system. This system comprises two receptors with their respective ligands and six high-affinity IGF binding proteins. Its action is mediated by binding to its specific receptor tyrosine kinase (IGFR-I), that initiates the activation of PI3K and /or MAPK pathway. In ovary, this growth factor was observed in different compartment of follicle (granulosa cells, theca cells and oocyte). IGF-I is the main cell survival factor in the ovary, it protects cell from apoptosis promoted by several agents. Activation of the IGF-I receptor is a particularly important survival-promoting signal during follicular development. The involvement of IGF-I in the early stages of folliculogenesis was evidenced by studies in which IGF-I increased follicular diameter, promoted functional integrity and antrum formation during preantral follicle in vitro culture. In addition, this growth factor acts in oocyte maturation, and its role is related with gonadotropin action and steroidogenesis process. The KL also known as stem cell factor, steel factor or mast cell growth factor, consists of a pleiotropic protein which acts on target cells by binding to its receptor tyrosine kinase, c-kit, mainly by the activation of PI3K-AKT-FKHRL1 and PTEN pathway. In the ovary, the KL mRNA expression has been detected in the granulosa cells of many species and it can be expressed as either a membrane-bound (KL-1) or a soluble protein (KL-2) according to the mRNA processing after the end of transcription. The KL was the first growth factor described as important during the follicular activation. Studies have evidenced its action in survival and proliferation of granulosa cells, theca cells recruitment from ovary stroma and in steroidogenesis regulation. Moreover, KL stimulates the antrum formation and meiosis resumption of oocyte from in vitro grown FOPA Moreover, KL stimulates the antral cavity formation and meiosis resumption of oocyte from in vitro grown FOPA. Furthermore, there is evidence that this growth factor acts on ovulation process. Conclusions: This review, we could conclude that IGF-I promote the development of preantral and antral follicles and KL has demonstrated an essential role in follicular development, acting at different follicle stages. Both, KL and IGF-I play an important role in ovarian follicle development, including the cell proliferation, differentiation and survival. Moreover, both factors act in the process of steroidogenesis, oocyte maturation, and ovulation. According to contents of present review, the compression of different pathway of these growth factor acts in ovarian cells has been clarified with success through the in vitro culture and molecular biology techniques.