Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 23, 2003
Publication Date: November 1, 2003
Citation: Roberts, A.J., Echternkamp, S.E. 2003. Insulin-like growth factor binding proteins in granulosa and thecal cells from bovine ovarian follicles at different stages of development. Journal of Animal Science. 81(11):2826-2839. Interpretive Summary: Ovarian follicular development is a prerequisite for normal reproductive function in animals. Mechanisms regulating follicular development are complex, involving hormones from tissues outside the ovary, as well as within individual follicles. Changes in follicular fluid levels of insulin-like growth factor binding proteins (IGFBPs) are important in regulating whether an individual follicle continues to develop or dies. The current study determined amounts of the different types (2 through 5) of IGFBPs produced by cells from follicles at different stages of development to determine if local production of these proteins accounts for changes in fluid levels of these proteins. Cells from large healthy follicles contained 2 to 20-fold less IGFBPs than cells from small, medium and large atretic follicles. The IGFBP activity detected in fluid from these follicles paralleled changes observed in cells. The only exception to this was that IGFBP-4 binding activity was lowest in fluid from large healthy follicles, yet this protein was much greater in cells from these follicles compared other follicles. Thus, follicular fluid levels of IGFBP-4 in large follicles appear to be regulated by specific proteases that digest this protein. Collectively, these results indicate that developmental changes in follicular fluid levels of IGFBPs appear to be controlled at least in part by alterations in the local synthesis of these IGFBPs. This study adds to our knowledge of what controls follicular development. Such knowledge is critical towards identifying abnormalities that contribute to reproductive losses.
Technical Abstract: Ovarian follicular development is associated with changes in follicular fluid levels of insulin-like growth factor binding proteins (IGFBPs). To provide knowledge on intra-follicular IGFBP production, levels of IGFBP binding activities and mRNAs were determined in granulosa and theca interna cells isolated from small (< 6 mm), medium (6 to < 8 mm), and large (>/= 8 mm) follicles. Thecal and granulosa cells from large healthy follicles contained 2 to 20-fold less (P < 0.05) IGFBP-2, -3, and IGFBP-5 than cells from small, medium, and large atretic follicles. Thecal cells from small, medium, and large atretic follicles contained more (P < 0.05) IGFBP-3 and -4 than granulosa cells from these follicles, whereas, granulosa cells from these follicles contained more IGFBP-2 activity than thecal cells. Differences in IGF binding activity detected by ligand blot procedures were paralleled by differences in levels of mRNA for the respective IGFBPs. Developmental differences in IGFBP activity in fluid from follicles were associated with changes observed in granulosa and(or) thecal cell homogenates, with exception that IGFBP-4 binding activity was low in fluid from large healthy follicles, but IGFBP-4 mRNA and binding activity were much greater in granulosa cells from these follicles compared to granulosa cells from other follicle classifications. It is concluded that developmental changes in follicular fluid IGFBP-2 and -5 binding activities are controlled in part by alterations in the local synthesis of these IGFBPs. In contrast, IGFBP-4 binding activity in fluid from large follicles appears to be regulated by posttranslational mechanisms, possibly specific proteases.