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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 α-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 α-subunit is required for secretion of the glycoprotein hormone β-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 Islet 1, and those that stimulate proliferation, including Nupr1, E2f1, and Etv5. We characterized the expression and function of a novel, overexpressed 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.

Original publication

DOI

10.1210/en.2016-1183

Type

Journal article

Journal

Endocrinology

Publication Date

09/2016

Volume

157

Pages

3631 - 3646

Keywords

Adenoma, Amino Acid Sequence, Animals, Cell Proliferation, Endoplasmic Reticulum, Endoplasmic Reticulum Stress, Female, Gene Expression, Gene Expression Profiling, Glycoprotein Hormones, alpha Subunit, Hypothyroidism, Male, Mice, Molecular Sequence Data, Pituitary Neoplasms, Thyrotrophs, Thyrotropin, beta Subunit, Transcription Factors, Transcriptional Elongation Factors, Unfolded Protein Response