Chronic effect of insulin-like growth factor I on renin synthesis, secretion, and renal function in fetal sheep

2001 ◽  
Vol 281 (1) ◽  
pp. R318-R326 ◽  
Author(s):  
Amanda C. Marsh ◽  
Karen J. Gibson ◽  
June Wu ◽  
Phillip C. Owens ◽  
Julie A. Owens ◽  
...  

In the adult, insulin-like growth factor I (IGF-I) increases glomerular filtration rate (GFR) and renal blood flow (RBF) during both acute and chronic treatment. To study its effects on the developing kidney, chronically catheterized fetal sheep (120 ± 1 days gestation) were infused intravenously for up to 10 days with 80 μg/h IGF-I ( n = 5) or vehicle (0.1% BSA in saline, n = 6). In contrast to previous acute studies in adult rats and humans, after 4 h of IGF-I fetal GFR and RBF were unchanged. Fractional sodium reabsorption increased ( P< 0.05). However, by 4 days, GFR per kilogram had risen by 35 ± 13% ( P < 0.05), whereas RBF remained unchanged. Tubular growth and maturation may have occurred, as proximal tubular sodium reabsorption increased by ∼35% ( P < 0.005). Therefore, despite a marked increase in filtered sodium (∼30%, P < 0.05), fractional sodium reabsorption did not change. Although the effects of IGF-I on renal function were delayed, plasma renin activity and concentration were both elevated after 4 h and remained high at 4 days ( P < 0.05). Despite this, arterial pressure and heart rate did not change. Kidneys of IGF-I-infused fetuses weighed ∼30% more ( P = 0.05) and contained ∼75% more renin than control fetuses ( P < 0.005). Thus, in the fetus, the renal effects of long-term IGF-I infusion are very different from the adult, possibly because IGF-I stimulated kidney growth.

FEBS Letters ◽  
1996 ◽  
Vol 388 (2-3) ◽  
pp. 155-160 ◽  
Author(s):  
Bohuslav Dvořák ◽  
Audrey L. Stephana ◽  
Hana Holubec ◽  
Catherine S. Williams ◽  
Anthony F. Philipps ◽  
...  

1996 ◽  
Vol 270 (5) ◽  
pp. R1148-R1155 ◽  
Author(s):  
F. Lok ◽  
J. A. Owens ◽  
L. Mundy ◽  
J. S. Robinson ◽  
P. C. Owens

Insulin-like growth factor I (IGF-I) is required for normal fetal growth and skeletal maturation in late gestation, because null mutations of the IGF-I gene in mice reduce fetal weight and retard ossification of bones. To determine if, conversely, increased abundance of IGF-I promotes fetal growth and skeletal maturation, fetal sheep were infused intravascularly with recombinant human IGF-I (n = 7) (26 +/- 3 micrograms. h-1.kg-1) from 120 to 130 days gestation and compared with controls (n = 15). IGF-I infusion increased plasma IGF-I concentrations by 140% (P = 0.002) and weights of fetal liver, lungs, heart, kidneys, spleen, pituitary, and adrenal glands by 16-50% (P < 0.05). Weights and/or lengths of the fetus, placenta, gastrointestinal tract, individual skeletal muscles, and long bones were unchanged by IGF-I. However, IGF-I increased the percentage of proximal epiphyses of long bones present (P < 0.05) and their cross-sectional areas by 15 to 38% (P < 0.05). These results show that IGF-I promotes growth of major fetal organs, endocrine glands, and skeletal maturation in vivo, consistent with IGF-I actively controlling and not merely facilitating fetal growth. The variable response of different tissues may partly reflect tissue specificity in growth requirements for additional factors.


1987 ◽  
Vol 115 (1) ◽  
pp. 135-139 ◽  
Author(s):  
G. Norstedt ◽  
C. Möller

ABSTRACT Primary liver cells from adult rats were used to study the hormonal regulation of mRNA coding for insulin-like growth factor I (IGF-I). IGF-I mRNA could be detected at a low concentration in liver cells prepared from hypophysectomized rats and cultivated for 3 days. When these cells were exposed to GH on the second day, a dose-dependent increase in IGF-I mRNA was observed. The continuous presence of serum was not a prerequisite for this response, since GH also induced IGF-I mRNA in a defined hormone-supplemented medium. It is concluded that GH can induce IGF-I mRNA in the liver by a direct mechanism. J. Endocr. (1987) 115, 135–139


1997 ◽  
Vol 272 (6) ◽  
pp. F698-F703 ◽  
Author(s):  
M. S. Wong ◽  
S. Sriussadaporn ◽  
V. A. Tembe ◽  
M. J. Favus

Dietary P restriction increases renal 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] biosynthesis through stimulation of proximal tubule 25-hydroxyvitamin D3-1 alpha-hydroxylase (1-OHase). Because insulin-like growth factor I (IGF-I) is required for 1-OHase stimulation by low-P diet (LPD) and because 1-OHase stimulation by low-Ca diet and parathyroid hormone is lost with aging, studies were undertaken to determine whether 1-OHase activity during LPD is impaired with age and whether IGF-1 can increase 1-OHase activity in adult rats. Five days of LPD increased in vitro 1-OHase activity in young (97.3 +/- 13.5 vs. 49.7 +/- 6.8 pg.mg protein-1.5 min-1, P < 0.005) but not adult (42.3 +/- 5.37 vs. 41.2 +/- 8.9) rats. In LPD-fed adult rats, recombinant human IGF-I (rhIGF-I, 1.4 mg.kg body wt-1.day-1) for 72 h increased 1-OHase (65.2 +/- 5.88 vs. 95.1 +/- 7.26 pg.mg protein-1.5 min-1, P < 0.005). The results show that the rise in 1-OHase activity during LPD is lost in adult rats and that rhIGF-I can overcome the inhibition and stimulate renal 1-OHase activity to levels observed in young animals. The studies indicate that the age-related loss of 1-OHase activity is reversible.


1991 ◽  
Vol 128 (3) ◽  
pp. 347-357 ◽  
Author(s):  
B. H. Breier ◽  
B. W. Gallaher ◽  
P. D. Gluckman

ABSTRACT This report describes essential requirements for the validation of a radioimmunoassay (RIA) for insulin-like growth factor-I (IGF-I) and presents solutions to some problems and pitfalls commonly observed. The preparation of IGF-I to be used as radioligand or standard has to be selected carefully since some IGF-I preparations are contaminated with variants which demonstrate different potencies for different antisera used in the RIA. Accurate assessment of IGF-I levels in blood plasma requires an efficient extraction method for the IGF-binding proteins (IGFBPs). Extraction methods to remove the influence of IGFBPs in the RIA were compared using blood plasma of considerable differences in IGF-I/IGFBP ratios. Acidification of plasma before column chromatography on Sephadex G-75 (G75) is generally considered to be the most reliable extraction method, but it is very time-consuming. The acid–ethanol extraction (AE) of plasma is not valid in many situations. Non-parallel displacement to the IGF-I standard was observed with AE-extracted plasma samples in the RIA. In addition, a comparison of IGF-I values obtained in the RIA after AE or G75 extraction of fetal ovine plasma has shown no significant correlation. We report an extraction technique based on a modified AE extraction followed by cryo-precipitation (AEC). AEC extraction on blood plasma reduced residual IGFBPs to a level that did not interfere in the assay. Furthermore, AEC-extracted plasma samples showed parallel displacement in the RIA to highly purified preparations of authentic IGF-I. We observed high correlations, with a slope close to unity, of IGF-I values obtained in the RIA using the AEC or G75 extraction for plasma from different species including adult and fetal sheep, rat, mouse and man. The AEC extraction provides a rapid and simple alternative to G75 extraction for blood plasma from a variety of species provided that high-affinity antisera are used for the RIA. Journal of Endocrinology (1991) 128, 347–357


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