A non-responsive alpha-secreting thyrotropic tumor contains T3 receptors and a TSH beta gene.
We have recently described a mouse pituitary tumor line, MGH 101A which is derived from a TSH-producing thyrotropic tumor line and now produces only the alpha-subunit of the glycoprotein hormones. In these studies, we have investigated the mechanism for the lack of TSH beta subunit expression in MGH 101A, as well as the failure of triiodothyronine (T3) to regulate alpha-subunit. Southern blot analysis of restriction endonuclease-digested DNA from MGH 101A tumors indicates the presence of a TSH beta gene and an alpha-subunit gene indistinguishable from those in a TSH-producing tumor (TtT 97). In MGH 101A tumors, however, TSH beta gene transcription was minimal (4 +/- 2 ppm) relative to alpha-subunit (283 +/- 29 ppm) and there was no significant difference in transcription after T3 treatment. In contrast, TtT 97 tumors had nearly equal rates of alpha-subunit (375 +/- 25 ppm) gene transcirption, and T3 respectively. The MGH 101A suppressed the transcription of alpha-subunit and TSH beta genes by 76% and 87%, respectively. The MGH 101A tumor contained T3 receptors with a binding affinity (1.54 X 10-10M) similar to receptors on TtT 97 tumors (1.78 X 10-10M), but at a lower concentration (2800 vs. 4000 sites/cell). We conclude that the absence of TSH beta production in MGH 101A tumors is not due to the absence of the TSH beta gene, but perhaps to some other modification of the gene structure. This could also explain the failure of MGH 101A tumors to respond to T3, since they do contain T3 receptors of normal affinity.
D000818:Animals; D002460:Cell Line; D004262:DNA Restriction Enzymes; D005786:Gene Expression Regulation; D005796:Genes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis*; D011988:Receptors, Thyroid Hormone; D013972:Thyrotropin / Q000235:genetics* / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013972:Thyrotropin; D004262:DNA Restriction Enzymes