title: Effects of elevated serum insulinlike growth factor-II on growth hormone and insulinlike growth factor-I mRNA and secretion.
abstract: 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)
authors.affiliation: Department of Pediatrics, Medicine, and Laboratory Animal Medicine, Stanford University, CA.
authors.forename: D M
authors.initials: DM
authors.lastname: Wilson
authors.forename: S N
authors.initials: SN
authors.lastname: Perkins
authors.forename: J A
authors.initials: JA
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: Seelig
authors.forename: S A
authors.initials: SA
authors.lastname: Berry
authors.forename: T E
authors.initials: TE
authors.lastname: Hamm
authors.forename: A R
authors.initials: AR
authors.lastname: Hoffman
authors.forename: R L
authors.initials: RL
authors.lastname: Hintz
authors.forename: R G
authors.initials: RG
authors.lastname: Rosenfeld
mesh_terms: 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*
chemical_list: 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