Pure alpha-subunit producing tumor derived from a thyrotropic tumor: impaired regulation of alpha-subunit and its mRNA by thyroid hormone.

We have recently described a mouse pituitary tumor line which produces only the alpha-subunit of the glycoprotein hormones. This tumor line may be a useful animal model to study autonomous pituitary tumors which secrete only alpha-subunit. Our pure alpha-subunit producing tumor was derived from a thyrotropic tumor which secreted intact TSH as well as free alpha-subunit. Our current studies compare the regulation of alpha-subunit biosynthesis in a conventional thyrotropic tumor and the alpha-subunit producing tumor. Thyroxine or triiodothyronine administration to mice bearing the alpha-subunit producing tumor resulted in no change in plasma alpha-subunit concentration, and a 10-19% reduction in tumor alpha-subunit mRNA concentration that was not statistically significant. In contrast, thyroxine administration to mice bearing the thyrotropic tumor resulted in an 81% reduction in plasma alpha-subunit concentration, and a 75% reduction in tumor alpha-subunit mRNA concentration (P less than 0.01). Other studies using a cDNA specific for thyrotropin-beta (TSH beta) failed to detect TSH beta mRNA in the alpha-subunit producing tumor, while TSH beta mRNA was easily detected in the conventional thyrotropic tumor. We conclude that during the development of the alpha-subunit producing tumor from a thyrotropic tumor, loss of TSH beta mRNA was also associated with an impaired capacity for thyroid hormone to decrease concentrations of alpha-subunit mRNA.