We have utilized active immunization against growth hormone releasing factor (GRF) to investigate relationships among somatotropin (ST), insulin-like growth factor-I (IGF-I), IGF binding proteins (IGFBP) and ovarian function in heifers. Active immunization against GRF (GRFi) has been demonstrated to abolish episodic release of ST and decrease serum concentrations of IGF-I. In initial experiments investigating onset of puberty, breeds of heifers differing in growth rate and reproductive traits (Angus, Charolais and Simmental) were immunized against GRF or served as controls (immunized against carrier protein, human serum albumin, HSAi). GRFi decreased rate of muscle and skeletal growth, but increased deposition of adipose tissue. In Angus and Charolais, but not Simmental heifers, GRFi at 6 mo of age significantly delayed onset of puberty beyond 18 mo of age. Retrospective analyses of serum IGF-I revealed that GRFi heifers reaching puberty at a normal age had greater pre-treatment (6 mo of age) IGF-I than GRFi heifers in which puberty was delayed. Collectively, these results strongly indicate that the bovine hypothalamic-hypophyseal-ovarian axis is particularly sensitive to changes in metabolism at or near 6 mo of age.
Another series of experiments tested the hypothesis that lowering serum IGF-I via GRFi initially at 3 mo of age would increase the percentage of Angus and Simmental heifers not reaching puberty. Three mo old Angus and Simmental heifers were assigned to GRFi (n = 18), HSAi (n = 14) or received no treatment (controls, n = 16). HSAi and GRFi heifers were unilaterally ovariectomized (ULO) at 6 mo of age. As anticipated, GRFi at a younger age increased percentage of heifers not reaching puberty; over 75% of control and HSAi heifers reached puberty by 14 mo.of age compared to 22% of GRFi heifers. Serum and follicular fluid (FFL; follicles ≤ 4 mm) concentrations of IGF-I were suppressed by GRFi. Serum, but not FFL concentrations of IGF binding protein-2 (IGFBP-2) were greater in GRFi than in HSAi heifers. GRFi delayed puberty apparently by suppressing follicular growth because number of follicles ≤7 mm was significantly lower in GRFi than in HSAi heifers. In conclusion, active immunization against GRF at 3 or 6 months of age delays puberty in beef heifers. Delayed puberty was preceded by suppression of follicular growth, and decreased concentrations of IGF-I in serum and follicular fluid. Collectively, these studies demonstrate that ovarian function between 3 and 8 mo of age and subsequent onset of puberty are particularly sensitive to changes in the ST-IGF-I axis
