Effect of active immunization against growth hormone releasing factor on concentrations of somatotropin and insulin-like growth factor I in lactating beef cows

Abstract

Two experiments were conducted to determine the effects of immunoneutralization of growth hormone-releasing factor [GRF(1–29)-NH 2] on concentrations of somatotropin (ST) and insulin-like growth factor I (IGF-I) in lactating beef cows. In Experiment 1, multiparous Hereford cows were immunized against 2 mg GRF(1–29)-(Gly) 4-Cys-NH 2 conjugated to human serum albumin (GRFi, n=3) or 2 mg human serum albumin (HSAi, n=3) at 52 ± 1 d prior to parturition. Boosters (1 mg) were administered on days 12, 40 and 114 postpartum (pp). Serum samples were collected at 15-min intervals for 5 hr on days 18, 46 and 120 pp, followed by administration (IV) of an opioid agonist (FK33-824; 10 μg/kg) and an antagonist (naloxone; .5 mg/kg) at hours 5 and 7, respectively. A GRF-analog ([desamino-Tyr 1, D-Ala 2, Ala 15] GRF (1–29)-NH 2; 3.5 μg/kg) and arginine (.5 g/kg) were administered at hour 10 on days 47 and 121, respectively. Percentage binding of [ 125I]GRF (1:100 dilution of serum) 28 d after primary immunization was greater in GRFi (14.3 ± 4.9) than in HSAi (.7 ± .3) cows. Binding increased to 29.3 ± 6.5% after first booster in GRFi cows. Episodic release of ST was abolished by immunization against GRF; concentration and frequency of release of ST were lower (P<.05) in GRFi than in HSAi cows on all days pp. Concentrations of IGF-I were lower in GRFi than in HSAi cows throughout lactation. Serum ST failed to increase following FK33-824 or arginine in GRFi; however, ST increased after both compounds in HSAi cows. Concentrations of ST following GRF-analog were greater (P<.05) in HSAi than in GRFi cows. Experiment 2 was conducted to determine if a lower dose of antigen and a single booster would be sufficient to lower ST and IGF-I in lactating cows. Multiparous Hereford and Angus cows were assigned to GRFi (n=6) or HSAi (n=6). Primary (1.2 mg) and booster (.5 mg) immunizations were administered −14 and 8 d from calving, respectively. Cows were restricted to 60% of recommended intake of energy during lactation in order to elevate concentrations of ST. Serum samples were collected at 15-min intervals for 6 hr on days 26, 50, 73, 90 and 109 pp. Two of six GRFi cows had binding less than 10% (1:1,000 dilution of serum) and were omitted from further analyses. Percentage binding at a 1:1,000 dilution was greater in GRFi (17.0 ± 4.7) than in HSAi (1.4 ± .4) cows at 89 d pp. Consequently, frequency of release, and concentration of ST and IGF-I were lower (P < .05) in GRFi than in HSAi cows. Concentrations of ST increased following FK33-824 in HSAi, but not GRFi cows. Across experiments, interval from calving to ovulation (estimated from weekly progesterone concentrations) was greater in HSAi than in GRFi cows. In conclusion, gestating-lactating beef cows were effectively immunized against GRF as evidenced by antibody binding of [ 125I]GRF, absence of pulsatile release of ST, low concentrations of ST and IGF-I and failure of ST to increase after IV opioid agonist or arginine.