Gene expression in mouse thyrotrope adenoma: transcription elongation factor stimulates proliferation

Differential gene expression study comparing choriogonadotropin alpha (Cga) gene deficient and wild type adult mouse pituitary. Thyrotrope hyperplasia and hypertrophy are common responses to primary hypothyroidism. To understand the genetic regulation of these processes, we studied gene expression changes in the pituitaries of Cga-/- mice, which are deficient in the common alpha subunit of TSH, LH and FSH. These mice have thyrotrope hypertrophy and hyperplasia and develop thyrotrope adenoma. We report that cell proliferation is increased, but the expression of most stem cell markers is unchanged. The alpha subunit is required for secretion of the glycoprotein hormone beta subunits, and mutants exhibit elevated expression of many genes involved in the unfolded protein response, consistent with dilation and stress of the endoplasmic reticulum. Mutants have elevated expression of transcription factors that are important in thyrotrope function, such as Gata2 and Isl1, and those that stimulate proliferation, including Nupr1, E2f1 and Etv5. We characterized the expression and function of a novel, over-expressed gene, transcription elongation factor A (SII)-like 5 (Tceal5). Stable expression of Tceal5 in a pituitary progenitor cell line is sufficient to increase cell proliferation. Thus, Tceal5 may act as a proto-oncogene. This study provides a rich resource for comparing pituitary transcriptomes and an analysis of gene expression networks. Total RNA was obtained from 8 week old Cga-deficient and littermate wild type mouse pituitary tissue. Total sample number was 24 as follows: 6 male and 6 female wild types, 6 male and 6 female mutants. Each sample was applied to an individual microarray.