Identification and partial purification of serum growth hormone binding protein in domestic animal species2

Abstract

The chemical nature and variations in serum concentrations of growth hormone binding protein (GHBP) from humans, rabbits, and rodents have been reported. To date little is known about the GHBP of domestic animals. Therefore, we initiated these studies to determine whether a serum GHBP was present in domestic animals and to purify the binding protein (BP) from serum of selected species. Using a dextran-coated charcoal separation assay, specific growth hormone (GH) binding was demonstrated in ovine, bovine, chicken, human, goose, porcine, and equine serum (listed in sequence from lowest to highest binding). Variation in BP activity was relatively high, both within and between species. Yearling ewes had higher serum GHBP than either prepubertal (4 mo) or older (5 yr) ewes. The GHBP was partially purified from chicken, ovine, and porcine serum using GH affinity chromatography. These BP had high affinity (Ka = 2 x 10(8) to 2 x 10(9) L/mol, depending on species) and low capacity (2 x 10(-10) to 5 x 10(-11) mol/unit of protein) for human GH but showed lower binding affinity for homologous GH (Ka = 2 x 10(7) L/mol). The porcine GHBP had the highest and ovine GHBP the lowest affinity for human GH. Other heterologous somatotropic hormones, ovine placental lactogen, and ovine GH displayed higher binding affinity to chicken and pig BP than the respective homologous hormones. Further chromatographic purification of the porcine GHBP resulted in an additional 1,000-fold purification. The estimated molecular weight of porcine GHBP is 50,000 to 60,000 Da. These results demonstrate that the serum from all domestic species tested contains a specific GH-binding moiety and that under the conditions described here human GH is a more efficient ligand than the homologous hormone.

Identification and Modulation of a Growth Hormone-Binding Protein in Rainbow Trout (Oncorhynchus mykiss) Plasma during Seawater Adaptation

“…Thus, considering the homologous hormones, these binding properties appear to be more related to a putative circulating GH-BP. Similar data with higher binding affinity of heterologous hormones for the GH-BP compared with homologous GH (approximately 100-fold) has been reported in chicken and other domestic animals (Davis et al, 1992). Mutational and structural studies have demonstrated that one hGH molecule binds to two molecules of hGHBP, through two regions called binding sites 1 and 2 (Goffin et al, 1996).…”

“…The growth hormonebinding protein (GH-BP) which represents the extracellular domain of the GH receptor (Leung et al, 1987). Serum GH-BP has been identified in numerous domestic animals, from poultry to mammals (Davis et al, 1992). Regulation of the expression of GH-BP appears to be also under the control of multiple hormonal, nutritional, or environmental factors, although its biological function remains to be clarified (Postel-Vinay, 1996).…”

Long-Term Growth after Hypophyseal Stalk Transection and Hypophysectomy of Beef Calves

“…Exogenous GH enhances retention of nitrogen, increases body weight gain in growing ruminants, and increases milk yield in dairy cows (57,59,60). A complex interaction between pituitary GH, the IGFs, their receptors, and their binding proteins in the regulation of statural growth applies in cattle and rats but remains unexplained in guinea pigs (61)(62)(63). In immature hypophysectomized rats, daily injection of recombinant human GH (rhGH) or rhIGF-I initially caused rapid and equivalent weight gains, but growth-promoting effects of IGF-I progressively decreased after 4 days (58).…”

Physiology and pathophysiology of growth hormone-binding protein: Methodological and clinical aspects

“…GHBP has been determined in plasma from a number of domestic animals [111][112][113][114][115], but the majority of animal studies have been performed in rats and mice. Due to significant differences in the regulation of GHBP levels between rodents and humans it is difficult to apply results from animal studies to humans, although similarities do exist.…”