Hormonal regulation of thyrotropin alpha and beta subunit mRNAs

We have examined the effects of 3,5 3'-triiodo-L-thyronine (T3), dexamethasone, bromocriptine, thyrotropin releasing hormone (TRH) and estrogen on the levels of pituitary alpha and TSH-beta protein and mRNA levels in hypothyroid mice. After 3 days of treatment with T3 (0.5 micrograms/100 g body weight) serum TSH, alpha and TSH-beta levels were 77%, 79% and 44% of control, respectively. Pituitary alpha and TSH-beta mRNA content was estimated by dot blot hybridization of total RNA with 32P-labelled alpha and TSH-beta plasmid probes. There was no change in alpha mRNA after 3 days of T3 treatment but TSH-beta mRNA had decreased to 60% of control. With T3 at 2 micrograms/100 g body weight for 3 days, TSH protein was 27% of control and TSH-beta was undetectable, but there was no change in alpha. TSH-beta mRNA was decreased to 40% of control at 1 day and was barely detectable at 3 days, whereas alpha mRNA was 70% of control at 1 day and 42% at 3 days. Dexamethasone and bromocriptine caused no consistent change in pituitary levels of alpha and TSH-beta mRNA. Treatment with TRH caused small increases in serum TSH and in both alpha and TSH-beta mRNA levels. Estrogen treatment increased serum TSH and subunit levels and TSH-beta mRNA, but not alpha. We conclude that thyroid hormones decrease alpha and beta subunit mRNA levels discordantly in both the hypothyroid pituitary and in thyrotropic tumors and that the suppressive effect of thyroid hormone is the major regulator of TSH.