Hormonal Regulation of Thyrotropin Alpha and Beta Subunit mRNAs

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