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IGF-II in the rat is an embryonic/fetal growth factor. Transcription of its gene falls abruptly in the liver at about 18–20 days postnatally. In an attempt to elucidate the mechanisms controlling this phenomenon, we used Northern analysis to investigate the effect of corticosterone and thyroid hormones (tri-iodothyronine and tetra-iodothyronine) on hepatic IGF-II mRNA levels. The administration of either corticosterone or tri-iodothyronine to 8-day-old pups resulted in a significant decrease in IGF-II mRNA when the animals were examined on day 12 of life. Adrenalectomy, thyroidectomy or adrenalectomy combined with thyroidectomy were, however, without effect. Our results indicate that glucocorticoid and thyroid hormones are not the exclusive regulators of IGF-II gene transcription in the rat liver, but participate in this process, which appears to involve multifactorial interactions.