The Fetal Rat Binding Protein for Insulin-Like Growth Factors is Expressed in the Choroid Plexus and Cerebrospinal Fluid of Adult Rats

Insulin-like growth factors (IGFs) I and II are considered to be autocrine regulators of bone cell function. Recently, we demonstrated that IGF-I induces IGF-binding protein-5 (IGFBP-5) expression in cultures of osteoblast-enriched cells from 22-day fetal rat calvariae (Ob cells). In the present study, we postulated that IGFs play an autocrine role in the maintenance of IGFBP-5 basal expression in Ob cells. IGFBP-2 and -3, at concentrations that bind endogenous IGFs, decreased IGFBP-5 mRNA levels, as determined by Northern blot analysis, and protein levels, as determined by Western immunoblots of extracellular matrix extracts of Ob cells. IGFBP-2 and -3 in excess inhibited IGFBP-5 heterogeneous nuclear RNA levels, as determined by RT-PCR, and did not alter the half-life of IGFBP-5 mRNA in transcriptionally arrested Ob cells. In conclusion, blocking endogenous IGFs in Ob cells represses IGFBP-5 expression, suggesting that IGFs are autocrine inducers of IGFBP-5 synthesis in osteoblasts.

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Nucleotide Sequence and Expression of a cDNA Clone Encoding a Fetal Rat Binding Protein for Insulin-like Growth Factors

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)83711-5 ◽

1989 ◽

Vol 264 (9) ◽

pp. 5148-5154 ◽

Cited By ~ 5

Author(s):

A L Brown ◽

L Chiariotti ◽

C C Orlowski ◽

T Mehlman ◽

W H Burgess ◽

...

Keyword(s):

Growth Factors ◽

Nucleotide Sequence ◽

Cdna Clone ◽

Binding Protein ◽

Fetal Rat ◽

Insulin Like Growth Factors

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Influence of insulin-like growth factor-binding protein-2 on plasma clearance and transfer of insulin-like growth factors-I and -II from plasma into mammary-derived lymph and milk of goats

Journal of Endocrinology ◽

10.1677/joe.0.1500121 ◽

1996 ◽

Vol 150 (1) ◽

pp. 121-127 ◽

Cited By ~ 6

Author(s):

C G Prosser ◽

J Schwander

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Plasma Clearance ◽

Binding Protein ◽

Plasma Concentrations ◽

Insulin Like Growth Factor ◽

Factor Binding ◽

Lactating Goats ◽

Igf I ◽

Insulin Like Growth Factors

Abstract Plasma clearance of insulin-like growth factors-I and -II (IGF-I and -II) and insulin-like growth factor-binding protein-2 (IGFBP-2) from lactating goats (n=4) was determined following a single intravenous injection of the corresponding 125I-labelled human protein. Transfer of these proteins out of the vascular space was monitored by their subsequent appearance in mammary-derived lymph and milk. Clearance of 125I-IGFBP-2 from circulation was 0·37 ± 0·06 ml/min/kg, which is markedly greater than that of 125I-IGF-I or -II (0·11 ± and 0·12 ± 0·01 ml/min/kg respectively). This was also reflected in longer elimination half-lives for IGF-I (353 ± 6 min) and -II (254 ± 8 min) compared with IGFBP-2 (110 ± 9 min). Three hours after injection of the 125I-labelled protein, the plasma:lymph ratio of trichloroacetic acid-precipitable radioactivity was 1·54 ±0·04, 3·3 ±0·6 and 4·1 ±0·4 for IGFBP-2, IGF-I and -II respectively. The form of 125I-IGFBP-2 in lymph was not different from that of plasma. Elevation of plasma concentrations of IGFBP-2 by its intravenous infusion significantly decreased plasma half-life of both IGF-I and -II (251 ± 8 and 198 ±7 min respectively). Although the amount and rate of transfer of IGF into mammary-derived lymph was decreased slightly by IGFBP-2, concentrations eventually obtained were not different from control. However, secretion of IGFs into milk was significantly reduced by IGFBP-2, particularly in the case of IGF-I. These results are consistent with the ability of all three compounds to cross the vascular endothelium intact and of IGFBP-2 to decrease the uptake of IGF by mammary epithelium and subsequent secretion into milk. IGFBP-2 may well have acted to target plasma IGF towards non-mammary tissues, thus explaining the more rapid plasma clearance of IGFs in the presence of elevated IGFBP-2. Journal of Endocrinology (1996) 150, 121–127

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