Insulin-Like Growth Factor I and Insulin-Like Growth Factor-Binding Proteins in Bovine Serum and Follicular Fluid before and after the Preovulatory Surge of Luteinizing Hormone1

Abstract

Previous studies have shown that concentrations of insulin-like growth factor (IGF)-binding proteins (BPs) in bovine follicles before the preovulatory surge of LH are inversely associated with estradiol concentrations, such that decreases in IGFBPs occur with advanced development of antral follicles and atresia is associated with increases in IGFBPs. In the present study, we evaluated serum and follicular fluid at different times after the preovulatory surge of LH to determine whether changes in IGF-I and IGFBPs are associated with the marked changes in the steroidogenic capacity that occur in follicle during this period. Serum and fluid from small follicles (> or = 5-mm diameter) and the preovulatory follicle were collected from cows at the onset of standing estrus or 8.5 and 20.5 h after administration of 100 micrograms GnRH at the onset of estrus (n = 4/time). Concentrations of IGF-I (determined by RIA) did not differ (p > 0.10) among times but were lower (p < 0.05) in fluid from small and preovulatory follicles than those in serum. Profiles of IGFBPs (evaluated by ligand blot analysis) differed among serum and fluid from small and preovulatory follicles. Preovulatory follicles contained IGFBP-3 with little or no other IGFBPs detected. Amount of IGFBP-3 and progesterone did not differ with time of sample collection, but a 13- to 15-fold reduction in estradiol-17 beta and androstenedione occurred between 8.5 and 20.5 h after the LH surge. Small follicles contained IGFBP-2, -3, -4, and -5 (determined by immunoprecipitation). The amount of 28-29-kDa IGFBPs (small form of IGFBP-5 and [or] glycosylated form of IGFBP-4) was inversely associated with concentrations of androstenedione. The 31-kDa form of IGFBP-5 was positively correlated with concentration of progesterone. Serum contained IGFBP-2, -3, and -4, but not IGFBP-5. Circulating IGFBP-2, but not other IGFBPs, decreased by 50% from estrus to 20.5 h after GnRH. In summary, amounts of IGF-I or IGFBPs in preovulatory follicular fluid did not change in response to an LH surge, even though estradiol and androstenedione decreased markedly. The absence of IGFBPs other than IGFBP-3 in bovine preovulatory follicles may allow for increased availability of IGF-I, which is proposed to be important for oocyte maturation and ovulation.

Molecular determinants of a competent bovine corpus luteum: first- vs final-wave dominant follicles

“…Elevated expression of IGFBP2 transcripts in group C DFs (Table 4) and IGFBP2 protein in follicular phase fluids (Fig. 3) is consistent with these observations but, on first inspection, is somewhat at odds with earlier studies that indicate that IGFBP2 levels in follicular fluids decrease in large oestrogen-active and pre-ovulatory follicles (Echternkamp et al 1994, Funston et al 1996. However, in contrast to previous work, this study compared DFs of equivalent size but at different stages of the oestrous cycle.…”

Frequency of luteinizing hormone pulses in cattle influences duration of persistence of dominant ovarian follicles, follicular fluid concentrations of steroids, and activity of insulin-like growth factor binding proteins

“…Activity of IGFBP-2, -4, and -5 was increased with atresia of dominant follicles and subordinate follicles compared with estrogen active dominant follicles, while follicular fluid concentrations of IGF-I and -II were relatively consistent in all types of follicles (de la Sota et al, 1996). There was also little variation in content of IGF-I in follicular fluid during different stages of the first wave of dominant follicle development during the estrous cycle (Badinga et al, 1992), and in preovulatory follicles around the time of behavioral estrus (Funston et al, 1996). Collectively, results from previous studies and the present study indicate that bioavailability of IGF-I in individual follicles may be regulated by IGFBPs and is associated with atresia of follicles.…”

“…Although growing follicles were increasing in size, follicular fluid concentrations of E 2 in these follicles were relatively less as compared with those of growing dominant and growing persistent follicles, but this may only be indicative of differences in developmental stages. An appropriate model to compare with growing and growing persistent follicles may have been previously described (Funston et al, 1996), in which preovulatory follicles contain greater concentrations of E 2 and less activity of IGFBPs in follicular fluid, similar to persistent follicles.…”

“…In sheep, slight, yet significant increases in IGFBP-3 activity occurred with increased follicular development (Monget et al, 1993). However, follicular fluid from preovulatory and non-ovulatory follicles of cattle had similar amounts of IGFBP-3 (Funston et al, 1996). It has been proposed (Grimes and Hammond, 1994) that follicular fluid IGFBP-3 may be derived from the vascularization, and that this protein may function as a transporter for IGF-I from blood into follicles.…”

“…These bands have previously been identified as IGFBP-3 (a doublet at 44 and 40 kDa), IGFBP-2 (34 kDa), IGFBP-5 (a doublet at 31 and 29 kDa), and IGFBP-4 (a doublet at 28 and 24 kDa) (Echternkamp et al, 1994;Funston et al, 1996). Binding by 28-29 kDa proteins (29 kDa form of IGFBP-5 and 28 kDa form of IGFBP-4) could not always be distinctly separated in the ligand blots, therefore, binding in the 28-29 kDa region was analyzed as one band.…”