Effects of elevated serum insulinlike growth factor-II on growth hormone and insulinlike growth factor-I mRNA and secretion.
The insulinlike growth factors (IGF) appear to exert feedback control over their own production. In an effort to determine the physiologic mechanisms for this feedback modulation, we utilized a previously developed in vivo model in which rIGF-II secreting tumor cells are transplanted into immunodeficient rats to form IGF-II secreting tumors. The tumor-bearing rat have serum IGF-II concentrations sevenfold greater than those in controls (119 +/- 16 ng/mL [mean +/- SE] v 17 +/- 2 ng/mL, P less than .0001). Serum IGF-I concentrations were reduced among the tumor-bearing rats (438 +/- 42 ng/mL v 606 +/- 32 ng/mL, P = .002) and were negatively correlated with IGF-II concentrations (r = -.47, P = .025), suggesting that IGF-II suppressed the secretion of IGF-I. Increased serum IGF-II concentrations, however, did not affect basal growth hormone concentrations (tumor-bearing, 44 +/- 12 ng/mL; control 33 +/- 6 ng/mL, P = 0.96). The GH response to GH releasing factor was likewise similar in both groups. Moreover, pituitary GH mRNA level were not different in the two groups, suggesting that IGF-II does not have a significant effect on GH secretion in this in vivo model. There was no association between serum glucose and serum IGF-I or IGF-II concentrations. To examine the effect of IGF-II on IGF-I production from the liver, we measured IGF-I mRNA levels in a subset of animals. Despite these differences in serum IGF-I concentrations, the tumor-bearing rats did not have significantly lower liver IGF-I mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Wilson
D M
DM
Department of Pediatrics, Medicine, and Laboratory Animal Medicine, Stanford University, CA.
Perkins
S N
SN
Thomas
J A
JA
Seelig
S
S
Berry
S A
SA
Hamm
T E
TE
Hoffman
A R
AR
Hintz
R L
RL
Rosenfeld
R G
RG
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002460:Cell Line; D005246:Feedback; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000097:blood* / Q000502:physiology; D008099:Liver / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000378:metabolism; D009384:Paraneoplastic Endocrine Syndromes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011923:Rats, Nude; D013002:Somatomedins / Q000096:biosynthesis* / Q000097:blood*
D001786:Blood Glucose; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone