title: Gene Expression in Mouse Thyrotrope Adenoma: Transcription Elongation Factor Stimulates Proliferation.
abstract: 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.
authors: Department of Human Genetics (P.G., M.S.C., S.A.C.), University of Michigan, Ann Arbor, Michigan 48109; Department of Physiology, Anatomy and Genetics (H.C.C.), University of Oxford, Oxford OX3 0RZ, United Kingdom; and Department of Internal Medicine, Metabolism, Endocrinology and Diabetes (A.A.), University of Michigan, Ann Arbor, Michigan 48105.
authors: Peter
authors: P
authors: Gergics
authors: Department of Human Genetics (P.G., M.S.C., S.A.C.), University of Michigan, Ann Arbor, Michigan 48109; Department of Physiology, Anatomy and Genetics (H.C.C.), University of Oxford, Oxford OX3 0RZ, United Kingdom; and Department of Internal Medicine, Metabolism, Endocrinology and Diabetes (A.A.), University of Michigan, Ann Arbor, Michigan 48105.
authors: Helen C
authors: HC
authors: Christian
authors: Department of Human Genetics (P.G., M.S.C., S.A.C.), University of Michigan, Ann Arbor, Michigan 48109; Department of Physiology, Anatomy and Genetics (H.C.C.), University of Oxford, Oxford OX3 0RZ, United Kingdom; and Department of Internal Medicine, Metabolism, Endocrinology and Diabetes (A.A.), University of Michigan, Ann Arbor, Michigan 48105.
authors: Monica S
authors: MS
authors: Choo
authors: Department of Human Genetics (P.G., M.S.C., S.A.C.), University of Michigan, Ann Arbor, Michigan 48109; Department of Physiology, Anatomy and Genetics (H.C.C.), University of Oxford, Oxford OX3 0RZ, United Kingdom; and Department of Internal Medicine, Metabolism, Endocrinology and Diabetes (A.A.), University of Michigan, Ann Arbor, Michigan 48105.
authors: Adnan
authors: A
authors: Ajmal
authors: Department of Human Genetics (P.G., M.S.C., S.A.C.), University of Michigan, Ann Arbor, Michigan 48109; Department of Physiology, Anatomy and Genetics (H.C.C.), University of Oxford, Oxford OX3 0RZ, United Kingdom; and Department of Internal Medicine, Metabolism, Endocrinology and Diabetes (A.A.), University of Michigan, Ann Arbor, Michigan 48105.
authors: Sally A
authors: SA
authors: Camper
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D059865:Endoplasmic Reticulum Stress; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics; D007037:Hypothyroidism / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010911:Pituitary Neoplasms / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D052684:Thyrotrophs / Q000378:metabolism*; D037322:Thyrotropin, beta Subunit / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D035602:Transcriptional Elongation Factors / Q000378:metabolism; D056811:Unfolded Protein Response
chemical_list: D015292:Glycoprotein Hormones, alpha Subunit; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C000620871:Tceal5 protein, mouse; D037322:Thyrotropin, beta Subunit; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors