Recombinant growth hormone enhances muscle myosin heavy-chain mRNA accumulation and amino acid accrual in humans.

Abstract

A potentially lethal complication of trauma, malignancy, and infection is a progressive erosion of muscle protein mass that is not readily reversed by nutritional support. Growth hormone is capable of improving total body nitrogen balance, but its role in myofibrillar protein synthesis in humans is unknown. The acute, in situ muscle protein response to an infusion of methionyl human growth hormone was investigated in the limbs of nutritionally depleted subjects during a period of intravenous refeeding. A 6-hr methionyl growth hormone infusion achieved steady-state serum levels comparable to normal physiologic peaks and was associated with a significant increase in limb amino acid uptake, without a change in body amino acid oxidation. Myosin heavy-chain mRNA levels, measured by quantitative dot blot hybridization, were also significantly elevated after growth hormone administration. The data indicate that methionyl growth hormone can induce intracellular amino acid accrual and increased levels of myofibrillar protein mRNA during hospitalized nutritional support and suggest growth hormone to be a potential therapy of lean body wasting.Cachexia in hospitalized patients frequently results in severe lean body wasting that may threaten survival. Skeletal muscle myofibrillar protein losses are particularly prominent in patients afflicted with infection, malignancy, and trauma. Under such circumstances, nutritional supplementation may not reverse these losses of skeletal muscle protein, despite massive caloric and protein intake (1). Additional anabolic stimuli have therefore been proposed to enhance the rate of skeletal muscle protein repletion (2-4), but to date none have been shown to positively effect cellular conditions for myofibrillar protein accrual in vivo.Growth hormone (GH) is presently used in the treatment of pituitary dwarfism (5). Although in vitro data are conflicting with regard to the direct anabolic properties of GH (6-8) and suggest that many of the biological activities of this hormone may be mediated by secondary mediators such as insulin-like growth factors (IGFs) (7)(8)(9), it is clear that administration of this peptide to animals (10) and humans (11) promotes weight gain and whole body nitrogen retention. However, a mechanistic analysis of these effects in humans has previously been limited partly by the restricted quantities of the hormone and by possible contaminants in pituitary extracts of this hormone (12). Human in vivo experiments are now feasible with the availability of recombinant DNA-produced GH. To examine whether an infusion of recombinant methionyl human GH (Met-hGH) may acutely produce intracellular conditions favorable for myofibrillar protein synthesis, we infused this hormone in hospitalized volunteers during intravenous nutritional repletion. MATERIALS AND METHODSSubjects. Six normal male adult volunteers (26.1 ± 1.2 years, 180 ± 2 cm, 73 ± 3 kg) were admitted to the Clinical Research Center ofThe New York Hospital-Cornell Medical Center (NYH-CMC) after giving informe...

Somatotropin-induced protein anabolism in hindquarters and portal-drained viscera of growing pigs

“…The substantial increase in blood flow contributed to the increase in the amount of phenylalanine utilized by the HQ in ST-treated pigs. This finding is consistent with previous studies and is believed to be a function of local tissue metabolism (4,16,22,24,25,33,45). The localized increase in blood flow to the HQ may be mediated also by the vasodilator properties of IGF-I (28), which can stimulate the pro- duction of endothelial nitric oxide and induce endothelium-dependent vasodilation (3,23,28).…”

Skeletal Muscle Performance in Adults with Growth Hormone Deficiency

“…Increased myosin mRNA expression in thigh muscle following GH treatment in malnourished adults [8] may reflect alterations in the content of contractile units in adults with GH deficiency compared to normals. Since the number of myofibres is considered to remain con stant in adulthood, reduction in cross-sectional size of a constant number of myofibres is more likley to accom pany adult GH deficiency than hypoplasia.…”

“…The role of GH in normal adults, however, is less clear. A role in the regulation of normal body composition has been suggested by the findings of increased lean body and muscle mass, and reduced fat mass following treatment of adults with GH deficiency with recombinant human GH for 4 or 6 months [4,5], Treatment of post-surgical [6], burnt [7], or malnourished [8] patients with GH has resulted in significant anabolic effects, but GH treat ment in starved, obese patients has shown only transient conservation of lean body mass [9]. Supraphysiological doses of GH given to trained athletes have been shown to increase lean tissue and thigh muscle mass [10].…”

Histology of Skeletal Muscle in Adults with GH Deficiency: Comparison with Normal Muscle and Response to GH Treatment

“…GH has anabolic effects in adults and children with GH deficiency [1,[3][4][5][6][7][8], in resistance-trained adults [16], in malnourished patients [17], and in elderly males [18], In the adults reported here, GH deficiency resulted in an 8% reduction in predicted mean lean body mass [3], of which the major component is skeletal muscle [2]. Thus, it may be predicted that adults with GH deficiency would have reduced skeletal muscle mass and mean fibre areas For analysis, data for males (■) and females (a) were pooled.…”