Differential tissue regulation of the insulin-like growth factors in rats bearing the MStT/W15 pituitary tumor.
The content of insulin-like growth factors, IGF-I and IGF-II, was measured in tissues of rats bearing a transplantable mammosomatotrophic tumor, MStT/W15. Serum IGF-I was elevated in tumor-implanted rats [2,557 +/- (SE) 419 vs. 891 +/- 100 ng/ml], and tumor tissue concentrations of IGF-I were increased (321 +/- 16 ng/g) in comparison to control liver tissue (160 +/- 5 ng/g) or control pituitary (80 +/- 3 ng/g). The IGF-I levels were significantly increased in most peripheral tissues in the tumor-bearing rats with the exception of the liver. In support of this finding, messenger RNA for prepro IGF-I was likewise not increased in the livers of tumor-bearing rats, nor was there an increase in the growth hormone-dependent IGF-binding protein, BP-3, in the liver or serum of these animals. All tumors had detectable levels of prepro IGF-I mRNA which was, however, less than 50% of that noted in normal control liver. The tumors also expressed an IGF-BP which was identified as IGF-BP-2 by immunoblotting. Serum concentrations of IGF-II were similar in control and tumor-bearing animals (approximately 70 ng/ml). IGF-II levels in the tumor (90 +/- 5 ng/g) were significantly higher than levels in control liver (34 +/- 2 ng/g), but similar to those found in normal pituitary (165 +/- 24 ng/g). In peripheral tissues, IGF-II concentrations were selectively increased in skeletal muscle and heart of tumor-bearing rats. These data demonstrate tissue-specific regulation of IGF-I and IGF-II. Paradoxically, the liver does not appear to be stimulated over control levels by high serum growth hormone levels, since neither IGF-I peptide, IGF-I mRNA, nor IGF-BP-3 levels are increased in livers of tumor-bearing rats. This suggests that the increase in serum IGF-I in these animals is due to increased production of IGF-I by the tumors themselves and by nonhepatic peripheral tissues and further that hepatic responsiveness to growth hormone is diminished in these tumor-bearing animals.
Division of Endocrinology, State University of New York at Stony Brook 11794, USA.
M C
MC
Gelato
J
J
Vassalotti
E
E
Spatola
C
C
Rutherford
K
K
Marsh
H E
HE
Carlson
D000818:Animals; D001835:Body Weight; D002460:Cell Line; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism; D009132:Muscles / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry; D009368:Neoplasm Transplantation; D009929:Organ Size; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011233:Precipitin Tests; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014158:Transcription, Genetic
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011388:Prolactin; D013006:Growth Hormone