Immunonegative "null cell" adenomas and gonadotropin (Gn) subunit (SUs) immunopositive adenomas share frequent expression of multiple transcription factors.

The differentiation of pituitary cells and human pituitary adenomas follow three cell lineages: GH-PRL-TSH, ACTH, and FSH/LH, which are regulated by a combination of various transcription factors and co-factors. We have used RT-PCR and immunohistochemistry to show that immunonegative, "null cell" adenomas are equipped with multiple transcription factors and co-factors. The "null cell" adenomas showed similar frequencies of transcription factors as did the gonadotropin subunit (GnSU)-positive adenomas, with the exception that there were fewer instances of SF1 in the former. We speculate, therefore, that null cell adenomas and GnSU-positive adenomas share common molecular mechanisms in functional differentiation, even though the former do not produce hormones. From the high frequency of various transcription factors, we also speculate that both null cell adenomas and GnSU-positive adenomas are derived from "committed" pituitary progenitor stem cells. The questions, why a certain proportion of these pituitary tumor groups lack hormone production and why they are molecularly more committed to Gn transcription, remain to be further investigated.