Mouse pituitary tumor line secreting only the alpha-subunit of the glycoprotein hormones: development from a thyrotropic tumor.
This report describes the conversion of a murine pituitary thyrotropic tumor (MGH 101) to a pure alpha-subunit-secreting tumor (MGH 101A) during a 6-yr period of serial transplantation. MGH 101 was a thyrotropic tumor originating from a hypothyroid mouse pituitary, growing only in hypothyroid hosts, and secreting large quantities of intact TSH and free alpha-subunit. Between the fourth and ninth transplantation generations, tumor TSH secretion declined progressively by at least 500-fold, to undetectable levels. In contrast, tumor secretion of free alpha-subunit decreased only 10-fold, and has since remained stable for nine transplantation generations. During the conversion to pure alpha-subunit secretion, MGH 101A exhibited growth in euthyroid as well as hypothyroid hosts, and increased its growth rate 2 to 3-fold. In contrast, the conventional thyrotropic tumor TtT 97 has maintained its secretion of both intact TSH and free alpha-subunit, its dependence on a hypothyroid environment, and its slower growth rate for nine generations. Gel chromatography of the media from tumor cell cultures confirmed that MGH 101A secreted only the free alpha-subunit, whereas TtT 97 secreted immunoactive TSH, TSH beta, and free alpha-subunit which eluted as separate peaks. We conclude that a dependent thyrotropic tumor has spontaneously developed into a pure alpha-subunit-secreting tumor which is independent of host thyroid function for its growth and alpha-subunit production.
D000818:Animals; D002460:Cell Line; D002850:Chromatography, Gel; D003470:Culture Media; D015292:Glycoprotein Hormones, alpha Subunit; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000378:metabolism*; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism; D013997:Time Factors
D003470:Culture Media; D015292:Glycoprotein Hormones, alpha Subunit; D010446:Peptide Fragments; D010908:Pituitary Hormones, Anterior; D013972:Thyrotropin