Effect of Ethanol on Plasma and Hepatic Insulin-Like Growth Factor Regulation in Pregnant Rats

1995 ◽  
Vol 19 (4) ◽  
pp. 867-873 ◽  
Author(s):  
Charles R. Breese ◽  
William E. Sonntag
1993 ◽  
Vol 138 (2) ◽  
pp. 327-336 ◽  
Author(s):  
S. E. P. Bastian ◽  
P. E. Walton ◽  
J. C. Wallace ◽  
F. J. Ballard

ABSTRACT To determine whether the changes in insulin-like growth factor-binding proteins (IGFBPs) and IGF-I levels during pregnancy in rats affect the clearance of IGFs from the circulation, we have measured pharmacokinetic parameters and the tissue distribution of radiolabelled IGF-I and LR3IGF-I, a potent analogue which has a markedly reduced affinity of binding to the IGFBPs. Intravenous boluses of radiolabelled growth factors were administered to catheterized virgin and age-matched pregnant rats on day 18 of gestation when plasma IGFBPs, in particular IGFBP-3, are dramatically reduced. IGF-I was cleared more rapidly from plasma in pregnant rats compared with the virgins; metabolic clearance rate (MCR) = 2·88±0·12 (s.e.m.) and 0·90±0·05 ml/min per kg respectively. Although LR3IGF-I was cleared more rapidly than IGF-I from plasma, similar clearance rates for the analogue were obtained in both pregnant and virgin animals, MCR = 9·19±0·15 and 9·84±0·28 ml/min per kg respectively. In virgin rat plasma, labelled IGF-I was mainly associated with the 150 kDa complex, whereas in pregnant rat plasma IGF-I was predominantly associated with lower Mr IGFBPs (approximately 30–50 kDa). The majority of LR3IGF-I was detected as free peptide. A larger proportion of the tracer was detected as small Mr breakdown products in plasma from rats under conditions of reduced binding to IGFBPs, e.g. during pregnancy or when LR3IGF-I was the labelled tracer, suggesting greater rates of IGF degradation. More LR3IGF-I tracer was detected in kidneys, ovaries and adrenals of virgin rats and in the ovaries and adrenals of pregnant rats, compared with IGF-I tracer. IGF-I radioactivity was greater than LR3IGF-I in caecum, brain, liver and heart in virgin rats and in kidneys, caecum, brain, liver, heart, placenta, fetus and fetal plasma of the pregnant rats. These results show that the reduction in IGFBP during pregnancy dramatically increased the clearance of IGF-I from the circulation towards that obtained with LR3IGF-I. The observation that less LR3IGF-I was detected in placenta, fetus and fetal plasma compared with IGF-I raises the possibility that the ability to bind IGFBPs during pregnancy may enhance IGF uptake by the conceptus. Journal of Endocrinology (1993) 138, 327–336


1990 ◽  
Vol 127 (3) ◽  
pp. 383-390 ◽  
Author(s):  
S. E. Gargosky ◽  
P. E. Walton ◽  
P. C. Owens ◽  
J. C. Wallace ◽  
F. J. Ballard

ABSTRACT Insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding proteins (IGFBP) were examined in rat serum during pregnancy and lactation. IGF-I concentrations determined after acid column chromatography of serum were low during the last third of pregnancy. IGF-II was undetectable in pregnant and non-pregnant rats. IGF-binding protein (IGFBP) concentrations, measured as high molecular mass activity in the IGF-I RIA and the IGF-II RRA of acid column fractions, paralleled the changes observed with IGF-I. Western ligand blot analysis of serum from non-pregnant rats revealed a 40–50 kDa IGFBP aligning with IGFBP-3, a smaller 28–30 kDa doublet and 24 kDa IGFBP. Serum from rats in late pregnancy lacked IGFBP-3, whereas the smaller IGFBP persisted during late pregnancy. IGFBP-3 reappeared in postpartum animals. The fall in serum IGF-I is consistent with a maternal catabolic state during late pregnancy which may maximize substrate availability for the developing fetus. Journal of Endocrinology (1990) 127, 383–390


2004 ◽  
Vol 39 (Supplement 1) ◽  
pp. S547
Author(s):  
P. Socha ◽  
R. Janas ◽  
A. Dobrza??ska ◽  
B. Koletzko ◽  
I. Broekaert ◽  
...  

1998 ◽  
Vol 36 (3) ◽  
pp. 379-394 ◽  
Author(s):  
Anselm P. D'Costa ◽  
David M. Prevette ◽  
Lucien J. Houenou ◽  
Siwei Wang ◽  
Kerstin Zackenfels ◽  
...  

1991 ◽  
Vol 130 (3) ◽  
pp. 395-400 ◽  
Author(s):  
S. E. Gargosky ◽  
J. A. Owens ◽  
P. E. Walton ◽  
P. C. Owens ◽  
J. C. Wallace ◽  
...  

ABSTRACT During late pregnancy in the rat, circulating levels of insulin-like growth factor-I (IGF-I) and some IGF-binding proteins (IGFBP) decline. The aim of the present study was to determine the relationship of GH to circulating IGF and IGFBP in the late-pregnant rat and to examine the effects on maternal, fetal and placental growth of preventing the decline in serum IGF and IGFBP concentrations. During the first 9 days of pregnancy, IGF-I concentrations increased from 340 to 500 μg/l. Recombinant human (rh) GH at 2·4 mg/kg per day and rhIGF-I at 1·4 mg/kg per day were infused into pregnant rats via osmotic mini pumps during the second half of pregnancy. After pump implantation on day 11 of pregnancy, only IGF-I infusion significantly increased circulating IGF-I. A maximum IGF-I concentration of 907 μg/l was measured on day 14 during treatment with IGF-I, after which the serum concentration decreased to 510 μg/l by day 20 of pregnancy. The serum IGFBPs were examined using a Western ligand blot technique. Infusion of neither GH nor IGF-I returned the IGFBPs to non-pregnant levels. Administration of IGF-I slightly increased IGFBP-3 and a smaller 32 kDa IGFBP at days 17 and 20 of pregnancy. Neither fetal nor placental weight was significantly different between treatment groups. However, administration of IGF-I significantly increased maternal weight gain during the 10-day treatment period. Thus, pregnant rats infused with IGF-I gained 99±4 g (mean ± s.e.m., n = 10) compared with rats treated with GH or vehicle which gained 72±4 g (n = 9) and 77±4 g (n = 10) respectively. The increase in maternal weight after administration of IGF-I was not due to increased litter size, fetal or placental weight. The increased maternal weight gain after IGF administration, without affecting fetal and placental weights, suggests a modification in the mode of maternal nutrient repartitioning during late pregnancy. Journal of Endocrinology (1991) 130, 395–400


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