Correlation between the biological and immunological activities of growth hormone circulating in rats bearing MtTW15 tumors.

Growth hormone-like activity was demonstrated in diluted plasma of rats bearing the GH-secreting tumor, MtTW15, using an in vitro bioassay. The bioassay used depends upon the ability of GH in vitro to stimulate the uptake of 3-0-methyl glucose (3-OMG) into the isolated diaphragm of the hypophysectomized rat. It was found that the effect of the diluted plasma on this system was qualitatively like that of rat pituitary GH. Theophylline, a drug which blocks the action of GH on 3-OMG uptake by the diaphragm but has no effect on the actions of insulin or somatomedin on this process, completely abolished the stimulatory action of the plasma on the transport of the sugar. Furthermore, antibodies against rat pituitary GH (ArGH) completely abolished the biological activity of the diluted plasma. When plasma was diluted to give specific concentrations of rat GH (rGH), as determined by radioimmunoassay (RIA), the plasma produced responses in the 3-OMG assay equivalent to those obtained with similar concentrations of pituitary rGH. A good correlation was also observed between the concentration of rGH in the plasma of tumor-bearing rats measured by RIA and by an in vivo bioassay in which the effects were determined of injections of diluted plasma into hypophysectomized rats on the subsequent incorporation of [3H]thymidine into costal cartilage. This in vivo biological activity was abolished by incubation of the plasma with ArGH prior to its injection into the test animals. Thus, these studies indicate that in rats bearing the MtTW15 tumor there is a good correlation between the biological and immunological activities of the rGH circulating the bloodstream.