Skip to main content
ARS Home » Research » Publications at this Location » Publication #118890
Title: LACK OF REGULATION OF GROWTH HORMONE (GH) BINDING PROTEIN BY GH IN TRANSGENIC PIGS OVEREXPRESSING GH GENES

Author
item CIFONE, D - UBA-CONICET
item DOMINICI, F - UBA-CONICET
item Pursel, Vernon
item TURYN, D - UNIV. DE BUENOS AIRES

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/4/2002
Publication Date: N/A
Citation: N/A

Interpretive Summary: This paper analyzed the regulation of the circulating growth hormone binding protein in transgenic pigs expressing heterologous growth hormone and found that although high circulating concentrations of growth hormone are attained in these animals, the circulating concentration of the growth hormone binding protein is not up-regulated as expected. Previous studies in pigs that focused on the regulation of growth hormone binding protein levels by exogenous pig growth hormone generated conflicting results, and no clear relationship between them could be established. The present data clearly indicates that the continuous presence of high levels of bovine, ovine and human growth hormones does not induce production of growth hormone binding protein in pigs, which is the opposite of results found in mice. Previous research has demonstrated that under specific conditions pig growth hormone is capable of inducing production of growth hormone binding proteins in pigs, therefore, our data adds to the previously raise hypothesis that the mechanism of growth hormone binding protein up- regulation by GH is species specific. These findings will be primarily of interest to other scientists conducting research on basic endocrinology.

Technical Abstract: Transgenic pigs expressing bovine, ovine or human growth hormone (GH) structural genes fused to mouse metallothionein-I (mMT-bGH), ovine metallothionein (oMT-oGH) or mouse transferrin (mTf-hGH) promoters were used to study the effects of GH on the regulation of serum GH binding protein (GHBP). In the pigs studied, circulating concentrations of GH ranged from 15 to 1923 ng/ml. Using chromatographic methods, specific binding of GH was detected in serum from normal pigs, but was apparently absent in serum from all the transgenic pigs used. In contrast to the negative results obtained in binding studies, the presence of GHBP in transgenic pig serum was detected by immunoblotting using a specific anti-GHBP antibody (aaGHBP). A broad specific 54 kDa band was detected in normal pig serum as well as in sera from mMT-bGH, oMT-oGH, and mTf-hGH pigs. To confirm these results, sera from transgenic mMT-bGH pigs and their rsibbling controls were subjected to immunoprecipitation with aaGHBP followed by immunoblotting with the same antibody. With this technique, we detected two specific bands of 53 and 45 kDa, which could represent different degrees of glycosilation of GHBP. As determined by densitometric analysis, the amount of GHBP in transgenic pig serum was similar to that detected in their respective controls. The amount of circulating GHBP remained unchanged even in oMT-oGH and mTf-hGH pigs that were exposed since birth to circulating concentrations of GH as high as 1900 ng/ml. Thus, we conclude that heterologous GHs do not act as modulators of the serum GHBP in pigs. Our data adds to the previously raised hypothesis that the mechanism of GHBP up-regulation by GH is species specific.