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Title: Effect of growth hormone administration to mature miniature Brahman cattle treated with or without insulin on circulating concentrations of insulin-like growth factor-I and other metabolic hormones and metabolites

Author
item Chase, Chadwick - Chad
item Elsasser, Theodore
item SPICER, L - Oklahoma State University
item RILEY, DAVID - Texas A&M University
item LUCY, M - University Of Missouri
item Hammond, Andrew
item OLSON, T - University Of Florida
item Coleman, Samuel

Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/14/2011
Publication Date: 6/20/2011
Citation: Chase, C.C., Elsasser, T.H., Spicer, L.J., Riley, D.G., Lucy, M.C., Hammond, A.C., Olson, T.A., Coleman, S.W. 2011. Effect of growth hormone administration to mature miniature Brahman cattle treated with or without insulin on circulating concentrations of insulin-like growth factor-I and other metabolic hormones and metabolites. Domestic Animal Endocrinology. 41(1):1-13.

Interpretive Summary: A line of miniature Brahman cattle at the USDA, ARS, STARS in Brooksville, Florida have been characterized as having normal proportioned growth but are approximately two-thirds in frame size and body weight as that of normal Brahman at maturity. Furthermore, these miniature Brahman were reported to have abnormally high circulating concentrations of growth hormone (GH) and abnormally low circulating concentrations of insulin like growth factor-I (IGF-I) compared to normal Brahman contemporaries. These hormone differences are similar to a condition in humans termed Laron dwarfism. Subsequent studies in reproduction and growth aspects were conducted to more fully understand the mechanism associated with this anomaly. Results from earlier studies indicated that administration of GH or increased endogenous GH did not elicit an effect on IGF-I in growing miniature animals. Furthermore, miniature Brahman had lower circulating concentrations of insulin and a blunted or delayed rise in insulin after meal feeding as compared to normal Brahman contemporaries. Therefore in this study, we hypothesized that IGF-I secretion could be enhanced by concomitant administration of exogenous GH and insulin, and neither alone would be effective. However, results indicated that in the miniature Brahman model, both GH and GH + insulin treatments increased IGF-I in mature cattle, suggesting that this line of Brahman cattle is capable of responding to bioactive GH. In a parallel study, we previously reported that miniature Brahman cattle were homozygous for a single nucleotide polymorphism in GH that encodes a mutation in an amino acid involved in binding of GH to the GH receptor.

Technical Abstract: Previously, we determined that a primary cause of proportional stunted growth in a line of Brahman cattle was related to an apparent refractoriness in metabolic response to growth hormone (GH) in young animals. The objective of this study was to determine the effect of administration of GH, insulin (INS), and GH plus INS to mature miniature Brahman cows (n = 6; 9.7 ± 2.06 yr; 391 ± 48.6 kg) and bulls (n = 8; 9.4 ± 2.00 yr; 441 ± 54.0 kg) on circulating concentrations of metabolic hormones and metabolites, primarily IGF-I and IGF-I binding proteins. We hypothesized that IGF-I secretion could be enhanced by concomitant administration of exogenous GH and INS, and neither alone would be effective. Animals were allotted to a modified crossover design that included four treatments: control (CON), GH, INS, and GH + INS. At the start of the study, one-half of the cattle were administered GH (Posilac; 14-d slow release) and the other one-half served as CON for 7 days. Beginning on day 8, and for 7 days, INS (Novolin L) was administered (0.125 IU/kg BW) twice daily (0700 and 1900) to all animals; hence the INS and GH + INS treatments. Cattle were rested for 14 days and then were switched to the reciprocal crossover treatments. Blood samples were collected at 12-h intervals during the study. Compared to CON, GH treatment increased (P < 0.01) mean plasma concentrations of GH (11.1 vs. 15.7 ± 0.94 ng/mL), INS (0.48 vs. 1.00 ± 0.081 ng/mL), IGF-I (191.3 vs. 319.3 ± 29.59 ng/mL), and glucose (73.9 vs. 83.4 ± 2.12 mg/dL), but decreased (P < 0.05) PUN (14.2 vs. 11.5 ± 0.75 mg/dL). Compared to INS, GH + INS treatment increased (P < 0.05) mean plasma concentration of INS (0.71 vs. 0.96 ± 0.081 ng/mL), IGF-I (228.7 vs. 392.3 ± 29.74 ng/mL) and glucose (48.1 vs. 66.7 ± 2.12 mg/dL), decreased (P < 0.01) PUN (13.6 vs. 10.4 ± 0.76 mg/dL), and did not affect GH (13.5 vs. 12.7 ± 0.95 ng/mL). In the miniature Brahman model, both GH and GH + INS treatments dramatically increased circulating concentrations of IGF-I in mature cattle, suggesting that this line of Brahman cattle is capable of responding to bioactive GH.