Experimental Hypersomatotropism: Serum Growth Hormone and Insulin, and Pituitary and Pancreatic Changes in MtT-W15 Tumor-Bearing Rats Before and After Tumor Removal[*]

Abstract

In Wistar/Furth rats inoculated with the growth hormone (GH) secreting tumor MtT-W15 the serum GH concentration paralleled the development of the tumor: it rose significantly 19 days after tumor inoculation and increased continuously thereafter, to a mean value above 400 ng/ml at eight weeks. An oral glucose load had no effect on circulating GH in normal rats, while in most tumor-bearing animals it was followed by increased circulating GH, resembling the "paradoxical response" described in human acromegaly. After removal of the tumor, circulating GH fell within minutes to normal or subnormal values. The pituitary of the host animal underwent a progressive atrophy which also paralleled the rise in circulating GH and was reflected by decreased weight, protein and GH content. All pituitary parameters returned progressively to normal during the nine days following tumor removal while the glucose tolerance and the insulin response to glucose stimulation decreased significantly although the islet volume and the pancreatic insulin content remained high. These results indicate (a) the MtT-W15 tumor-bearing rat is a useful experimental model of hypersomatotropism; (b) that the chronically elevated levels of serum GH lead to pituitary atrophy which in part could reflect a "feedback inhibitory" mechanism, (c) that most of these changes returned to normal shortly after removal of the tumor; (d) that the diabetogenic effect of GH on peripheral tissues is compensated for by the concomitant stimulation of the islets; (3) that GH might stimulate the mechanisms responsible for the synthesis and release of insulin differentially.

Key words

Hypersomatotropism - MtT-W 15 Tumor - Serum Growth Hormone - Serum Insulin - Islet Volume - Pancreatic Insulin Content

1 Supported by grant #1202 from the Medical Research Council of Canada and by Intramural Funds of The Hospital for Sick Children.

1 Supported by grant #1202 from the Medical Research Council of Canada and by Intramural Funds of The Hospital for Sick Children.

2 Research Fellow of the Medical Research Council of Canada. Present address: Children's Hospital, University of Helsinki, Helsinki 29, Finland.