Barbara H. Moreland

Growth hormone increases IGF-I, collagen I and collagen III gene expression in dwarf rat skeletal muscle

The effect of short-term treatment with biosynthetic growth hormone (GH) of male dwarf rats was studied in EDL and soleus muscles. In situ hybridisation revealed that in the untreated dwarf rat collagen I, collagen III and insulin-like growth factor-I (IGF-I) mRNA is mainly expressed by fibroblasts between the muscle fibre areas. Quantitative image analysis showed that, 8 h after a single GH injection, the level of mRNA for all three genes increased compared to the untreated dwarf animal. IGF-I mRNA levels were similar in normals and untreated dwarf rats but significantly increased 8 h after a single GH injection in EDL (P < 0.01) and soleus (P < 0.001). In untreated dwarf rats, collagen I and III gene expression was significantly less than in normal animals (P < 0.001). Collagen III gene expression also increased significantly 8 h after a single GH injection, in both muscles (P < 0.01). Collagen I gene expression showed significant increases 8 and 24 h after GH treatment in EDL (P < 0.01), although the increases seen in soleus did not reach significance. The effects of multiple GH injections (one, two or four) did not appear to be additive. The results of the time course studies are consistent with an intermediary role for IGF-I in the production of collagen in muscle.

Effects of hypophysectomy and growth hormone administration on the mRNA levels of collagen I, III and insulin-like growth factor-I in rat skeletal muscle.

The effect of short-term treatment of normal or hypophysectomized rats with biosynthetic growth hormone (GH) was studied in extensor digitorum longus and soleus muscles. In situ hybridization revealed that in normal rats, mRNA for collagen I, collagen III and insulin-like growth factor-I (IGF-I) are expressed by fibroblasts between the muscle fibre areas and that the specificity of this location was not altered by GH administration. Hypophysectomy appeared to cause a decrease in IGF-I and decreased collagen I and III gene expression (P < 0.001, P < 0.001, respectively). GH administration seemed to increase IGF-I mRNA levels in all the animals studied. Quantitative image analysis that GH administration to hypophysectomized rats caused an increase in collagen I gene expression after 2 days (P < 0.05) and an increase in collagen III gene expression after 4 days (P < 0.05). The results indicate that the fibroblast cells are an important target for the action of GH on skeletal muscle and that the fibroblasts respond to GH by increases in the expression of mRNA for collagen I and collagen III.

Enhancement of the autocatalytic activation of trypsinogen to trypsin by bile and bile acids

The activation of trypsinogen to trypsin in the small intestine can occur by the action of enterokinase or, alternatively, as an autocatalytic process catalysed by trypsin itself. We have found that bile salts and human bile cause a significant enhancement of the autocatalytic activation of trypsinogen. This effect is dependent on the calcium ion concentration and is most marked around pH 5.4 and 7.8. An optimum concentration exists for each bile salt at which the greatest enhancement occurs. At this concentration, certain bile salts have been shown to produce activation effects of up to 55-fold. It is suggested that this activation of the autocatalytic process by bile plays an important role in protein digestion in the small intestine, since it has been shown previously that duodenal trypsin levels are abnormally low in patients with an impairment of bile secretion.

HUMAN GROWTH HORMONE TREATMENT ENHANCES DEPOSITION OF COLLAGEN IN RAT SKELETAL MUSCLES

Publisher Summary This chapter describes the human growth hormone (hGH) treatment enhances deposition of collagen in rat skeletal muscles. Hind limb muscles - gastrocnemius, soleus and extensor digitorum longus (EDL) were studied for the effects of human growth hormone injected daily to hypophysectomized (hx) rats. In response to hGH, the weights of these muscles increased and morphological/biochemical changes and fiber type changes were observed. The observations on the changing pattern of collagen deposition are reported. Hx rats were maintained for 14 days before subcutaneous injection with pituitary hGH, recombinant DNA hGH or diluent for 7 days and they were then killed and hind limb muscles were excised. Sections from both diluent-treated hx and normal rats showed the presence of collagen in discrete areas confined to the perimyseum regions, whereas the sections from hGH-treated rats showed larger localized patches of collagen extending into areas between the individual muscle fibers. After SDS Polyacrylamide gel electrophoresis of muscle extracts, an additional protein band of high molecular weight was consistently evident in samples obtained from pituitary hGH-treated or rDNA hGH-treated hx rats.