Effect of in utero ethanol exposure on the postnatal ontogeny of insulin-like growth factor-1, and type-1 and type-2 insulin-like growth factor receptors in the rat brain.
There is convincing evidence that alcohol consumption during pregnancy causes major CNS abnormalities; however, the molecular and cellular basis of these dysfunctions is currently not understood. This study examined the effects of prenatal ethanol exposure on the expression of insulin-like growth factor-1 messenger RNA and type-1 and type-2 receptor protein and messenger RNA expression in the developing rat brain. Mothers were maintained on an ethanol containing liquid diet from day 2 of pregnancy through parturition and the offspring were killed at birth, 10, 20 and 40 days of age. Insulin-like growth factor-1 messenger RNA, and insulin-like growth factor receptors demonstrated developmentally dependent expression in specific brain regions throughout the postnatal period of CNS maturation. Insulin-like growth factor-1 gene expression in the brain, as analysed by dot-blot hybridization, was greatest at birth, and decreased 61% in ad libitum and pair-fed animals by 20 days of age. In contrast, ethanol-treated animals exhibited only a 25% decrease in insulin-like growth factor-1 messenger RNA levels during the same period. This delay in insulin-like growth factor-1 messenger RNA maturation may be related to a developmental delay in CNS development in the prenatally ethanol exposed offspring. Prenatal ethanol exposure did not alter the observed localization of insulin-like growth factor-1 messenger RNA. While alterations were observed in long-term insulin-like growth factor-1 messenger RNA regulation, quantitative receptor autoradiography and in situ hybridization demonstrated no alterations in either type-1 or type-2 insulin-like growth factor receptor populations in ethanol-treated animals. Changes in hepatic and plasma insulin-like growth factor-1 and insulin-like growth factor-binding protein regulation have also been observed in these animals, suggesting changes in protein translation and the autocrine/paracrine actions of this peptide. The present study demonstrated that insulin-like growth factor-1 messenger RNA and insulin-like growth factor receptors are regionally expressed during early postnatal development and that ethanol administration influenced the long-term regulation of insulin-like growth factor messenger RNA levels in the brain without affecting either its localization or insulin-like growth factor receptor populations.(ABSTRACT TRUNCATED AT 400 WORDS)
Breese
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Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157.
D'Costa
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Sonntag
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D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism*
D017451:Receptors, Somatomedin; D000431:Ethanol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II