A study was made of the acute effects of growth hormone on the rate of leucine incorporation into protein of various tissues of hypophysectomized rats in "i"o. The rats were injected with bovine growth hormone intravenously or intraperitoneally for various periods of time, and then the rate of protein synthesis was assessed by pulse-Iabeling pro teins with L-leucine>-14C administered intravenously through a tail vein. Growth hormone stimulated leucine incorporation into the total TCA-precipitable protein of thigh muscles 30 min, but not 15 min, after its administration. The stimulatory effect was still evident at 6 and 24 hr after hormone iqjection. These observations are similar to those previously made with diaphragm muscle. In contrast, no stimulation of leucine incorporation into proteins of the heart was seen 0.25, 0.5, I, 3, 6, or 24 hr after a single injection of a large dose of growth hormone. In another experiment, the rate of leucine incorporation into proteins of several tissues was assessed by the pulsC>-labeling technique after 30 min of exposure to growth hormone in "i"o. Once again, the hormone increased (by 67%) the rate of leucine incorporation in the protein of both the thigh muscle and the diaphragrn. While no significant stimulation of protein labeling was evident in the thymus, kidney or brain at this time, growth hormone enhanced leucine incorporation into hepatic protein by 150%. Neither thymidine faotor activity nor the concentration of immunoreactive insulin was increased in the plasma of hypophysectomized rats 30 min after they received an injection of growth hormone. Thus, these results suggest that the acute stimulatory effects of pituitary growth hormone on protein synthesis in skeletal and diaphragmatic muscle and in the liver are not media ted by thymi4ine factor or insulin.

The effect of the acute intravenous administration of bovine growth hormone (bGH) to female hypophysectomized rats on the ability of ribosomes isolated from their thigh muscles to incorporate 3H-leucine and 3H-puromycin into protein in vitro was studied. Ribosomes prepared from the muscles of animals that had received bGH (200 microgram) 30 min before sacrifice were more active in incorporating leucine and puromycin into protein than the controls. However, no effect of the hormone on leucine incorporation was seen 15 min after its injection, suggesting some lag period in its course of action on ribosome function. In experiments dealing with the ability of the ribosome preparations to incorporation puromycin into protein, it was found that at the completion of the reaction, ribosomes made from the muscles of bGH-treated rats had incorporated 22% more tracer into protein than the controls, suggesting that these preparations contained a larger population of ribosomes actively engaged in protein synthesis. This conclusion was also supported by the finding that sucrose density gradient profiles of ribosome preparations from the hormone-treated rats had a greater proportion of ribosomes in the polyribosome fraction than those of the controls. From these and other observations made in this study, it would appear that the acute effect of growth hormone on the function of rat skeletal muscle ribosomes is to increase the fraction of ribosomes active in peptide synthesis.

Acute treatment of ob/ob mice with S-carboxymethylated hGH (RCM-hGH), a diabetogenic derivative of GH which lacks significant insulin-like and growth-promoting activities, results in an increase in fasting plasma insulin and blood glucose levels and enhanced peripheral tissue insulin resistance. Plasma insulin level increases within 3 h after RCM-hGH is administered, whereas increased blood glucose concentration and enhanced peripheral tissue insulin resistance became evident 6 h after the hormone derivative is given. The lag period seen in the manifestation of these diabetogenic effects of RCM-hGH is consistent with the time required for gene expression. Therefore, the present study was undertaken to determine whether the above acute responses to the diabetogenic action of RCM-hGH would be expressed in ob/ob mice in which protein synthesis was blocked with cycloheximide. Female ob/ob mice were given either saline or cycloheximide (0.1 mg/g BW) ip and 1 h later were fasted and treated with either saline or 200 micrograms RCM-hGH ip. The mice were given a second injection of cycloheximide during the middle of the hormone treatment period to insure that protein synthesis remained blocked for the entire 6 h. In the animals not receiving cycloheximide, fasting plasma insulin level and blood glucose concentration were markedly elevated 6 h after the injection of RCM-hGH. Also, the GH derivative attenuated the ability of insulin added in vitro to stimulate glucose oxidation by adipose tissue segments isolated from the animals.(ABSTRACT TRUNCATED AT 250 WORDS)