Insulin-like growth factor I increases renal 1,25(OH)2D3 biosynthesis during low-P diet in adult rats

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.

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 ◽  
...  

1991 ◽  
Vol 130 (2) ◽  
pp. 245-250 ◽  
Author(s):  
A. Hofig ◽  
F. A. Simmen ◽  
F. W. Bazer ◽  
R. C. M. Simmen

ABSTRACT The effects of insulin-like growth factor-I (IGF-I) on aromatase P450 activity and steroid production in preimplantation pig conceptuses were evaluated in vitro. Conceptuses recovered from gilts on days 10 and 12 of pregnancy were incubated for 6 h in modified Eagle's Minimum Essential Medium (MEM) plus IGF-I (0·1 μg/ml) or insulin (8·5 μg/ml), and conceptuses were monitored for their ability to convert [1,2-3H]β-testosterone into oestrogens. Aromatase activity of day-10 conceptuses was low and unaffected by IGF-I or insulin. In contrast, basal aromatase activity in day-12 conceptuses was about threefold higher and was further increased by IGF-I (P < 0·02), but was unaffected by insulin. To determine whether higher aromatase P450 activity was associated with increased oestradiol production, concentrations of oestradiol were determined by radioimmunoassay in culture medium of day-11 and -12 conceptuses, after incubation in MEM alone or in the presence of dehydroepiandrosterone (DHA, 1 μg/ml) with or without IGF-I (0·1 μg/ml) or insulin (0·1 or 8·5 μg/ml) for 24 h. Conceptuses in MEM plus DHA produced more oestradiol (P < 0·01) than those in MEM alone. Addition of IGF-I or insulin did not increase the effect of DHA. Basal oestradiol production was dependent on conceptus size; however, IGF-I or insulin did not affect basal or DHA-stimulated oestradiol production regardless of conceptus size. These findings demonstrate that IGF-I can modulate aromatase activity in vitro, without affecting overall de-novo steroidogenesis. Thus, the developmental increase in conceptus oestradiol production observed during early pregnancy in the pig may reflect synergistic interactions between IGF-I and other regulatory factors present within the conceptus and/or uterine environment. Journal of Endocrinology (1991) 130, 245–250


1991 ◽  
Vol 128 (3) ◽  
pp. 389-393 ◽  
Author(s):  
B. Houston ◽  
I. E. O'Neill

ABSTRACT Cultured chicken hepatocytes were used to investigate whether insulin and GH interact to regulate insulin-like growth factor-I (IGF-I) production in vitro. In the first set of experiments hepatocytes were preincubated for 6 h in hormone-free medium, and the effects of various combinations of insulin and GH on IGF-I production over the next 24 h were quantified by radioimmunoassay. Basal IGF-I production was 5·36 pg IGF-I/μg DNA and this was increased 1·31±0·13-fold (mean ± s.e.m.) by insulin, 1·90±0·24-fold by GH and 4·46±0·68-fold by a combination of insulin and GH. These results demonstrate that insulin and GH interact synergistically to stimulate IGF-I production in vitro. The synergism with GH occurred at physiological concentrations of insulin with half-maximal stimulation occurring at an insulin concentration of 6 ng/ml. In hepatocytes which had been exposed to insulin immediately before the start of the experiment, the presence of insulin was no longer required for maximal stimulation of IGF-I production by GH. This in-vitro system will facilitate the study of the molecular basis of the interaction between insulin and GH. Journal of Endocrinology (1991) 128, 389–393


2017 ◽  
Vol 29 (8) ◽  
pp. 1635 ◽  
Author(s):  
A. Dance ◽  
J. Kastelic ◽  
J. Thundathil

Beef and dairy bull calves fed a low-nutrition diet during early life had decreased concentrations of circulating insulin-like growth factor I (IGF-I), delayed increases in testosterone, smaller testes and delayed puberty compared with those fed high-nutrition diets. Although IGF-1 has important roles in Sertoli cell function in rats and mice, this has not been well documented in bulls. The objectives of this study were to: (1) isolate Sertoli cells from bull calves at 8 weeks of age, (2) culture them in vitro and (3) determine the effects of IGF-I, FSH and a combination of both hormones on cell proliferation. For Sertoli cell isolation, minced testicular tissues were treated with collagenase followed by trypsin and hyaluronidase to digest seminiferous tubules and release Sertoli cells. In this study, Sertoli cells were successfully isolated from 8-week-old Holstein bull calves (n = 4) and these cells were cultured for up to 8 days. A combination of IGF-I and FSH increased proliferation (~18%) and therefore cell number (1.5-fold) of prepubertal bovine Sertoli cells in culture, providing clear evidence that IGF-I has a similar role in bovine Sertoli cells as reported in rodents.


1998 ◽  
Vol 54 (2) ◽  
pp. 158-166
Author(s):  
R. G. MacDonald ◽  
R. H. McCusker ◽  
D. J. Blackwood ◽  
J. A. Vanderhoof ◽  
J. H. Y. Park

1992 ◽  
Vol 133 (2) ◽  
pp. 211-219 ◽  
Author(s):  
C. Duan ◽  
T. Hirano

ABSTRACT The possible roles of insulin-like growth factor-I (IGF-I) and insulin in regulating cartilage growth were studied in the teleost Anguilla japonica. Significant sulphation activity was found in the extracts of pancreas, liver and muscle, but not in those of kidney, intestine or spleen. The hepatic sulphation activity was significantly decreased by hypophysectomy or by fasting for 14 days, suggesting that this activity is regulated by pituitary function and nutritional status. Northern blot analysis revealed that the hepatic IGF-I mRNA in the eel consists of a major 4·0 kb band. This mRNA was GH-dependent and was significantly decreased by fasting for 14 days. On the other hand, fasting for 14 days had no significant effect on pancreatic sulphation activity. Pancreatic extracts from both intact and hypophysectomized eels exhibited equally significant stimulating activity. Addition of bovine or human insulin (1–250 ng/ml) to the culture medium significantly stimulated sulphate uptake in a dose-dependent manner. Teleost (coho salmon) insulin was as effective as bovine insulin. Bovine insulin was more effective than IGF-I at lower concentrations (1–4 ng/ml) but less effective at higher concentrations (10–250 ng/ml). These results indicate that not only IGF-I but also insulin are likely to be involved in the regulation of cartilage growth in the eel. Journal of Endocrinology (1992) 133, 211–219


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