Regulation of de novo biosynthesis of thyrotropin in normal, hyperplastic, and neoplastic thyrotrophs.

Abstract

We have studied the in vitro regulation of de novo biosynthesis of TSH and a-subunit in normal and hyperplastic rat pituitary cells and mouse thyrotropic tumor cells. Twenty-four-hour cell cultures were exposed to a variety of stimulatory and inhibitory agents. Total (intracellular plus extracellular) unlabeled TSH and α-subunit were measured by RIA, and [35S]methionine-labeled products were measured by immunoprecipitation. TRH (10 nin) and potassium (K+; 60 HIM) were found to stimulate total unlabeled TSH (40–86% increments above control levels) and a-subunit (13–86%) as well as labeled TSH (25–45%) and a-subunit (18–119%). Responses to TRH and K+ were greater for secreted products than intracellular products. TRH and K+ also caused increases in [35S]methionine- labeled total proteins, but not to statistical significance. In long term cultures of thyrotropic tumor cells, the response of secreted TSH to TRH increased with time. A peak response of a 180% increase in TSH was reached after 6 days of culture....