BETA-1,4-GALACTOSYLTRANSFERASE AND ALPHA-MANNOSIDASE-II MESSENGER-RIBONUCLEIC-ACID LEVELS INCREASE WITH DIFFERENT KINETICS IN THYROTROPHS OF HYPOTHYROID MICE

Hypothyroid animals secrete not only more TSH, but also qualitatively different TSH, with altered oligosaccharides. To explore the cellular mechanism of oligosaccharide modulation by thyroid status, 40 mice wer e treated without or with propylthiouracil (PTU), and pituitaries were removed after 1, 2, 3, 4, and 6 weeks. Serum T-4 levels confirmed tha t mice receiving PTU were hypothyroid even after only 1 week. Thyrotro phs and corticotrophs were identified in 5-mu m thick pituitary slices using immunocytochemistry; in situ hybridization was performed using S-35-labeled 48-mer DNA probes to beta-1,4-galactosyl-transferase and alpha-mannosidase-II messenger RNAs (mRNAs). A control probe also was used. Autoradiography was performed for 4 weeks. The cells and silver grains were scored, and the differences reported below were significan t by analysis of variance. Compared to euthyroid thyrotrophs, the beta -1,4-galactosyltransferase mRNA level in thyrotrophs increased 440% af ter mice received PTU for 1 week; the mean increase within thyrotrophs over the 6-week period was 173%, whereas there was little change in c orticotrophs. Compared to euthyroid thyrotrophs, the a-mannosidase-II mRNA level in thyrotrophs remained unchanged while mice received PTU f or 4 weeks, but then increased 150% after week 6 of PTU treatment. Thu s, thyroid status modulates mRNA levels of two glycosyltransferases in thyrotrophs, perhaps by affecting gene transcription or mRNA stabilit y. Moreover, the kinetics of the modulation of the two glycosyltransfe rase mRNAs differ. This is the first report of the modulation of these glycosyltransferase mRNA levels in thyrotrophs and may explain in par t the mechanism by which different isoforms of TSH are secreted in dif ferent physiological states.