A comparison of the growth-promoting, lipolytic, diabetogenic and immunological properties of pituitary and recombinant-DNA-derived bovine growth hormone (somatotropin)

Abstract

The physiological mechanisms by which growth hormone (somatotropin) exerts its several metabolic activities remain poorly understood. In particular, there is disagreement as to whether the diabetogenic and lipolytic activities of the hormone are intrinsic properties of the molecule or are the result of contamination with other pituitary components. The availability of recombinant-DNA-derived bovine growth hormone (rebGH) presented an opportunity to compare the biological activities of rebGH and pituitary bGH in the absence of pituitary contaminants. Pituitary bGH and rebGH were immunologically identical in the radioimmunoassay for bGH, and good agreement was obtained for the potency of the latter measured by radioimmunoassay (1.6 units/mg) and the dwarf-mouse bioassay (1.4 units/mg). The lipolytic activity in vitro was examined by measuring the release of glycerol from rat epididymal fat maintained in the presence of dexamethasone (0.2 microgram/ml) and the material to be tested (0.1 and 0.2 mg/ml). Although two preparations of pituitary bGH stimulated a significant (P less than 0.01) increase in glycerol production, neither rebGH nor recombinant-DNA-derived chicken GH was lipolytic. However, when rebGH was intravenously injected into three sheep (0.15 mg/kg), the increase in plasma nonesterified fatty acids was similar to that measured with the same dose of pituitary bGH. Insulin-tolerance tests were conducted in sheep before and after treatment with rebGH and pituitary bGH (four subcutaneous injections of 0.15 mg/kg). Although the effect of rebGH was less than that of the pituitary hormone, both significantly impaired the ability of insulin to lower the concentration of plasma glucose. These data suggest that the lipolytic and diabetogenic activities of bGH are intrinsic properties of the molecule. However, the lipolytic activity may only become apparent after either modification of the molecule in vivo or activation of a lipolytic intermediate.

A review of bovine growth hormone

“…In that study, milk lactose production represented a major use of lost glucose. McDowell et al (1987b) demonstrated that rbGH treatments reduced glucose uptake by the hindlimb muscle and increased glucose uptake by the mammary gland, lending further support that diabetogenesis is an inherent property ofthe rbGH molecule (Hart et al 1984). We additionally propose that IGF-I plays a fundamental role in the diabetogenic activities of rbGH.…”

“…By most immunological, receptor-binding, bioassay, and biopotency criteria, pituitary-and recombinant DNA-derived sources of bovine GH were originally shown to be similar or identical (Hart et al 1984;Wingfield et al 1987 Wingfield et al 1987). This suggests that several variants of bovine GH exist in vivo, each which could differ with regard to physiology.…”

Central infusion of leptin into well-fed and undernourished ewe lambs: effects on feed intake and serum concentrations of growth hormone and luteinizing hormone

“…The mechanism for this nutrition-dependant stimulation is currently unknown. As GH promotes lipolysis (Hart et al 1984, Dietz & Schwartz 1991, Richelsen 1997, perhaps the increased GH is meant to mobilize the excess fat represented by high leptin concentrations. Also of interest is the possibility that the increase in GH in leptin-treated diet-restricted lambs is a response associated with compensatory or 'catch-up' growth (Boersma & Wit 1997).…”

Digestibilidade e ganhos em peso de ovinos alimentados com diferentes fontes de volumosos e recebendo somatotropina recombinante bovina (rBST)

“…No início da década de 80, por intermédio da técnica do DNA recombinante, a somatotropina bovina começou a ser obtida em laboratório a partir de cultura de E. coli, conseguindo-se um produto sinté-tico de ação biológica idêntica à da proteína original, isenta de contaminantes e resíduos naturais (HART et al, 1984). O hormônio de crescimento ou somatotropina (GH ou ST) é uma proteína altamente complexa, constituída de 191 aminoácidos (WALLIS, 1973; GRAFF e LI, 1974), sendo naturalmente secretada pela glândula adenohipófise dos animais superiores.…”