ACTH and alpha-subunit are co-expressed in rare human pituitary corticotroph cell adenomas proposed to originate from ACTH-committed early pituitary progenitor cells.

The functional differentiation of pituitary cells and adenomas follows the combination of transcription factors and co-factors in three cell lineages [growth hormone-prolactin-thyroid-stimulating hormone lineage, adrenocorticotrophic hormone (ACTH)/pro-opiomelanocortin (POMC) lineage, and follicular stimulating hormone (FSH)/luteinizing hormone (LH) lineage], which include Pit-1, GATA-2, SF-1, NeuroD1/beta2, Tpit, ERalpha, and others. Only rarely are hormones from different lineages co-expressed in the same adenoma cells. Most corticotroph cell adenomas belonging to the ACTH/POMC lineage are mono-hormonal. In our study of 89 corticotroph cell adenomas, 5 cases expressed both ACTH and alpha-subunit; these adenomas did not express any other anterior pituitary hormones or subunits. To clarify the mechanism involved, we studied the transcription factors that regulate pituitary cell differentiation. NeuroD1 and T-pit, markers of the ACTH/POMC lineage, and SF-1 and DAX-1, related to the LH/FSH cell lineage were expressed in all cases. GATA2, a synergistic factor in the gonadotroph cell lineage with SF-1, was also expressed in three of five cases. As ACTH and alpha-subunit are the earliest hormones to appear during development, we speculate that these particular adenomas are derived from committed ACTH progenitor cells. The molecular process governing functional differentiation of these adenomas requires further investigation.