Biomedical subjects

S Triest

Publications and source records attributed to S Triest.

4 recordsLinked to original sources

PubMed1991

Evidence that pretranslational and translational defects decrease serum insulin-like growth factor-I concentrations during dietary protein restriction.

Dietary protein restriction causes GH resistance and decreases serum insulin-like growth factor-I (IGF-I) concentrations. To determine whether pretranslational or translational defects are involved in the decline of serum IGF-I concentrations during protein restriction, we measured hepatic IGF-I mRNA abundance together with the serum IGF-I peptide response to exogenous GH after 1 week of protein restriction (5% casein in diet; P5) in hypophysectomized rats. We compared these responses with those of hypophysectomized rats fed a protein-sufficient diet (15% casein in diet; P15) and given exogenous GH. A single injection of rat GH (200 micrograms/100 g BW) produced a comparable IGF-I mRNA increment in both groups (at 6 h, 7.8 +/- 1.1 arbitrary units in P5 vs. 8.2 +/- 1.1 in P15), but failed to raise serum IGF-I normally in the P5 group (at 6 h, 90 +/- 15 ng/ml in P5 vs. 216 +/- 63 in P15; P less than 0.01). The post-GH decline of the 7.5-kilobase (kb) IGF-I mRNA abundance was faster in P5 than in P15 animals. In another experiment in intact rats subjected to protein restriction, injections of pharmacological doses of rat GH (400 micrograms/100 g BW.day) for 1 week restored liver IGF-I mRNA abundance to normal without normalization of serum IGF-I (403 +/- 91 vs. 713 +/- 53 ng/ml; P less than 0.01). Our data suggest that 1) the machinery involved in the transcription of the liver IGF-I gene is intact in protein-restricted rats, because these animals retain the ability to muster normal IGF-I mRNA responses to high doses of exogenous GH; 2) the stability of the 7.5-kb IGF-I mRNA is probably decreased by the protein restriction, as suggested by the faster decline of the 7.5-kb transcript in P5 than in P15 hypophysectomized rats; and 3) the discrepancy between normal liver IGF-I mRNA abundance and low serum and liver IGF-I peptide concentrations suggests that translational stalling of the IGF-I mRNAs or increased serum IGF-I clearance is involved in the low serum IGF-I concentrations during dietary protein restriction.

Animals↗

PubMed1990

Divergent responses of serum insulin-like growth factor-I and liver growth hormone (GH) receptors to exogenous GH in protein-restricted rats.

Protein deprivation in young rats retards growth and decreases serum insulin-like growth factor-I (IGF-I) concentrations, neither of which is prevented by injections of GH once daily. Since four time daily injections of GH in hypophysectomized rats increase serum IGF-I concentrations more efficiently than single daily injections, we assessed whether this mode of GH delivery could overcome the GH resistance of protein malnutrition. Also, we evaluated whether continuous GH infusion could override this GH resistance. We fed 4-week-old female Wistar rats a low (5%) protein diet (P5) or a normal (15%) protein diet (P15) for 7 days. In a first experiment, rats fed a P5 diet received 40 or 400 micrograms/100 g BW.day rat GH (rGH) in four daily sc injections, while control P5 rats were injected at the same frequency with vehicle. In a second experiment, rats fed a P5 diet received 200 micrograms rGH/100 g BW.day by continuous infusion, while P5 sham-operated rats served as controls. IGF-I was measured by RIA on extracted serum, and free and total liver GH binding were determined by incubation of [125I]bovine GH with water- or MgCl2-treated homogenates, respectively. Neither continuous infusion nor repeated injections of rGH normalized the indices of growth or restored the serum IGF-I level to P15 control values. Injections of 400 micrograms rGH increased serum IGF-I 2-fold (P less than 0.01), but did not promote growth. Continuous GH infusion increased total and free liver GH binding to P15 control values, but had no effect on serum IGF-I. The discordance between liver GH binding and IGF-I confirms that a postreceptor defect is responsible for the GH resistance in protein restriction. These observations demonstrate that the consequences of protein restriction on growth are not overridden by intermittent or continuous administration of GH. The increase in IGF-I in response to 400 micrograms GH given intermittently in the absence of growth-promoting effects suggests that nutritional sufficiency is essential for IGF-I to promote growth.

Animals↗

PubMed1990

The decreased plasma concentration of insulin-like growth factor-I in protein-restricted rats is not due to decreased numbers of growth hormone receptors on isolated hepatocytes.

The resistance to GH and the low serum concentrations of insulin-like growth factor-I (IGF-I) that occur during fasting are accompanied by decreased GH receptors in liver homogenates. In protein restriction, however, serum IGF-I but not GH receptors are decreased, suggesting that a post-receptor defect exists. Because conclusions about the status of GH receptors during dietary manipulation are based on studies using liver homogenates, the present study was undertaken to determine whether changes in GH binding by homogenates are paralleled by changes in receptors on the cell surface considered to mediate the GH signal. Collagenase-dispersed hepatocytes or liver homogenates from 7-week-old female Wistar rats fed various diets were evaluated for changes in somatogenic receptors. Fasting for 24 h reduced significantly (P less than 0.001) the plasma concentrations of IGF-I (-31%). Likewise, GH-binding sites were decreased on hepatocytes (-55%; P less than 0.01) and in liver homogenates (-60%; P less than 0.001) compared with controls, as was the velocity of initial binding (-77%; P less than 0.001). Protein restriction for 1 week decreased plasma concentrations of IGF-I (-42%; P less than 0.001) but GH-binding sites were not significantly reduced on hepatocytes or in homogenates. The velocity of initial binding was also not decreased. We conclude that observations on changes in homogenate binding of bovine GH during dietary manipulation provide a reliable means of assessing changes in cell-surface GH receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

[Diabetes, malnutrition and growth retardation].

We investigated the cellular mechanisms responsible for growth hormone (GH) resistance in diabetes and malnutrition in the rat. In insulin-dependent diabetes, a post-receptor defect participates in GH resistance. During fasting, there is a loss of liver GH binding sites. Dietary protein restriction causes a post-receptor defect. This defect can be attributed to the combined effects of decreased liver IGF-I mRNA content and impaired message translation.

Animals↗