Mouse Pituitary Tumor Line Secreting Only the α-Subunit of the Glycoprotein Hormones: Development from a Thyrotropic Tumor*

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Abstract
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 4th and 9th 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 9 transplantation generations. During the conversion to pure .alpha.-subunit secretion, MGH 101A exhibited growth in euthyroid and 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 9 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. 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.
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