Diminished Insulin-like Growth Factor-1 Levels after Chronic Ethanol: Relationship to Pulsatile Growth Hormone Release

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Abstract
Previous studies have clearly demonstrated a reduction in plasma levels of IGF-1 in rats chronically fed an ethanol diet. The purpose of this study was to determine whether the reduction in IGF-1 was associated with alterations in growth hormone secretory dynamics. Male Sprague-Dawley rats were fed either a liquid diet containing 5% ethanol or an identical volume of diet made isocaloric with maltose-dextrin (pair-fed controls). After 4 months of continuous feeding, another group of animals of the same age was introduced into the colony and fed the maltose-dextrin diet ad libitum. All animals were atrial cannulated 4.5 months after the initiation of the experiment and serial samples of blood removed at 20-min intervals for periods up to 6 hr. Plasma was separated and growth hormone and IGF-1 concentrations determined by radioimmunoassay. Growth hormone secretory dynamics were analyzed by Cluster Analysis. Our results demonstrated that (a) chronic ethanol administration decreases plasma IGF-1 concentrations compared to either ad libitum or pair-fed control animals, (b) a reduction in dietary intake of approximately 33% reduces both the number of detectable growth hormone pulses and nadir concentrations of this hormone but has no effect on peak height, peak width, or area under the peak, and (c) ethanol feeding increases the amplitude of growth hormone pulses compared to pair-fed rats. We conclude that the decrease in plasma IGF-1 levels in ethanol as compared to pair-fed control animals is not caused by a further reduction in growth hormone secretory dynamics. Our results support the hypothesis that ethanol directly inhibits IGF-1 secretion from the liver.