Modulating peripheral gonadotrophin levels affects follicular expression of mRNAs encoding insulin-like growth factors and receptors in sheep

Evidence suggests that the insulin-like growth factor (IGF) system is involved in follicular growth and development in sheep. However, little information exists as to the role that key peripheral factors play in regulating the expression of IGF components within the follicle. The present study investigated the regulatory effects of FSH and LH on gene expression for IGF ligands and receptors in ovine follicles, using bovine follicular fluid (bFF) and gonadotrophin-releasing hormone antagonist (GnRHa) model systems to perturb endogenous gonadotrophin secretion. Gene expression studies were carried out using in-situ hybridisation with sheep-specific ribonucleotide probes. Treatment of ewes with bFF had no effect on IGF-I mRNA levels. However, IGF-II mRNA levels, particularly in small follicles, and follicular type II IGF-R gene expression significantly increased following bFF administration (P <0.001). Conversely, there was a significant (P <0.001) decrease in type I IGF-R mRNA levels after only 12 h of bFF treatment, especially in healthy follicles, although this was transient and was followed by a significant (P <0.01) increase in gene expression levels by 60 h of bFF treatment. Treatment of ewes with GnRHa resulted in a significant increase in mRNA levels encoding IGF-I (P <0.001), IGF-II in early atretic and large follicles (P <0.05), and type II IGF-R in healthy and early atretic follicles (P <0.001). In contrast, GnRHa administration decreased type I IGF-R gene expression levels after 60 h of treatment (P <0.001). These data highlight the roles that endogenous FSH and LH play in regulating IGF ligand and receptor gene expression in the sheep follicle.