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Maternal Zinc Deprivation and Interleukin-1 Influence Metallothionein Gene Expression and Zinc Metabolism of Rats^1,2,

Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611

The influence of maternal dietary zinc intake and recombinant human interleukin-1 (rhIL-1) administration on metallothionein gene expression and the distribution of ⁶⁵Zn were investigated. Pregnant rats were fed diets containing 1, 5, 30 or 180 mg Zn/kg diet in an equalized regime from d 13–20 of gestation. Metallothionein gene expression was examined by Northern blot and dot blot hybridization using combined 60-mer oligonucleotides specific for rat metallothionein-1 and -2 genes. Expression was progressively depressed in the fetal livers and livers and kidneys of dams fed diets marginal (5 mg/kg) and deficient (1 mg/kg) in zinc content. Administration of rhIL-1 increased expression in maternal liver, placenta and in fetal liver of dams fed adequate or deficient diets. Kinetics of intravenously administered ⁶⁵Zn showed that in response to rhIL-1, there was a higher uptake by the maternal liver and bone marrow with less ⁶⁵Zn uptake by bone, intestine and plasma activity compared to controls. No change was observed in ⁶⁵Zn taken up by the placenta or transferred to the fetus. Alteration of metallothionein gene expression could represent, in part, the mechanism whereby altered effects of zinc metabolism and function are mediated during fetal development.

KEY WORDS: • metallothionein • zinc • gene expression • interleukin-1 • development

¹ This research was supported by National Institutes of Health Grant No. DK 31127 from the National Institute of Diabetes and Digestive and Kidney Diseases, and Boston Family Endowment Funds.

² A preliminary report of these experiments was presented at the 1988 Annual Meeting of the American Institute of Nutrition, FASEB, Las Vegas, NV, May 1–5. [Huber, K. L., Leinart, A. S. & Cousins, R. J. (1988) Maternal zinc deprivation and interleukin-1 influence maternal and fetal metallothionein gene expression and kinetics of zinc metabolism. FASEB J. 2: A634.]

³ To whom reprint requests and correspondence should be directed.

Manuscript received 10 June 1988. Revision accepted 5 August 1988.