The rat islet cell line, RIN, established from a transplantable, radiation-induced islet cell tumor represents a unique model to study mechanisms in the control of insulin secretion and biosynthesis. In this study, we have examined the effects of glucose on the protooncogene expressioN and cell growth using a clonal strain of RIN cell, RINr, under serum-free and glucose-free conditions. After 24 h pretreatment, cells were treated with different concentrations of glucose for up to 24 h and then subjected to RNA analysis. Agarose gel electrophoresis of total RNA extracts of RINr cells, followed by hybridization with v-myc DNA yielded a 2.4 kilobase c-myc messenger RNA (mRNA) transcripts. After 24 h pretreatment with serum-free and glucose-free medium, RINr cells expressed a low level of c-myc mRNA transcripts. An increase in c-myc transcripts was detectable within 30 min of D-glucose (200 mg/dl) addition, reaching a maximum of 10-fold within 2 h. Glucose stimulated the steady state of c-myc mRNA transcripts in a dose-responsive manner without any change of gamma-actin mRNA levels after 2 h of treatment. The level of c-myc transcripts then declined as the cells proceeded through G1 to the cycle. [3H]Thymidine uptake into DNA was dramatically increased after 24 h of glucose addition, suggesting that glucose itself stimulates DNA synthesis in RINr cells. These results indicate that glucose-induced proliferation of RINr cells is associated with the stimulation of c-myc gene expression.

We have already demonstrated the inhibitory effect of interleukin 1 on thyroglobulin gene expression. Recent availability of thyroid peroxidase cDNA has allowed us to investigate the regulation of thyroid peroxidase gene. Therefore, the regulation of thyroid peroxidase mRNA by interleukin 1 in cultured human thyrocytes was investigated. Thyrocytes dispersed from thyroid tissues from patients with Graves' disease were incubated with TSH with or withtout recombinant human in-

Insulin-like growth factor-1 (IGF-1) is synthesized primarily by the liver in response to growth hormone (GH). Thyroid hormone plays a major role in mediating pituitary GH secretion. In order to clarify the effect of thyroid hormone on IGF-1 gene expression, we measured hepatic IGF-1 mRNA levels in rats with thyroid dysfunction. Female Wistar rats were rendered hypothyroid by surgical thyroidectomy or hyperthyroid by daily injections of thyroxine (12 micrograms/day) for 2 weeks. Northern gel analysis of hepatic poly (A) RNA revealed the multiple sizes of the RNA transcripts ranging from 1.6 to 9.0 kb. After 4 weeks, hepatic IGF-1 mRNA levels were suppressed in hypothyroid rats, to less than 20% of control euthyroid animals. These suppressed mRNA levels were restored to euthyroid levels by thyroid hormone replacement for 2 weeks. Hyperthyroid rats, however, did not contain altered levels of hepatic IGF-1 mRNA as compared to euthyroid rats. The gamma-actin mRNA hybridization signal was not altered in hypothyroid or hyperthyroid rats. These results suggest that thyroid hormone regulates the in vivo expression of hepatic IGF-1 mRNA, probably through the mechanism of GH regulation.