Expression Profiling Analyses of Gonadotropin Responses and Tumor Development in the Absence of Inhibins

• Published in: Endocrinology (Philadelphia) 2003-10, Vol.144 (10), p.4492-4507
• Main Authors: Burns, Kathleen H, Owens, Gabe E, Ogbonna, Samuel C, Nilson, John H, Matzuk, Martin M
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Neoplasms - etiology; Adrenal glands; Amino acids; Androgens - biosynthesis; Animal models; Animals; Bcl-2 protein; Biological and medical sciences; Biological effects; Carrier Proteins - physiology; Cell adhesion; Cell adhesion molecules; Cell culture; Cell Cycle; Cell Cycle Proteins - physiology; Composition effects; DNA microarrays; Female; Follicle Stimulating Hormone, beta Subunit - deficiency; Forkhead protein; FOXO1 protein; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Genes; Gonadotropins; Gonadotropins - metabolism; Gonadotropins, Equine - pharmacology; Granulosa Cells - metabolism; Hybridization; Inhibin; Inhibins - deficiency; Luteinizing Hormone, beta Subunit - metabolism; Male; Mice; Mice, Knockout; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Oligonucleotides; Oocytes - cytology; Ovarian Neoplasms - etiology; Ovaries; Ovary - metabolism; Pituitary; Pituitary (anterior); Protein transport; Proteins; Proto-Oncogene Proteins c-bcl-2 - physiology; Retinoblastoma; Retinoblastoma-Binding Protein 7; RNA, Messenger - metabolism; Sertoli Cells - metabolism; Teratocarcinoma; Theca Cells - drug effects; Transgenic mice; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2003-0476

Transgenic mice with engineered disruptions in bidirectional endocrine signaling between the pituitary and gonad have shed light on the specific effects of the loss of function of gonadotropins and inhibins. These models are valuable tools for studying ovarian biology because they phenocopy specific pathological states and have variations in ovarian tissue composition that allow us to identify genes expressed in specific cell types. We have used emerging mRNA expression profiling technologies to gain a more comprehensive view of genes that are expressed in the mammalian ovary and adrenal gland in the FSHβ and inhibin α knockout mouse models. Oligonucleotide array hybridization experiments using Affymetrix GeneChip technology and NIA 15K murine cDNA microarray studies identified hundreds of transcripts differentially expressed compared with wild type, over 30 of which were selected for further characterization by Northern blot analyses. Additionally, we performed in situ hybridization studies to localize 10 mRNAs, melanocyte-specific gene 1, amino acid transporter SN2, overexpressed and amplified in teratocarcinoma (Bcat1), Forkhead box protein FOXO1, 24p3, vascular cell adhesion molecule, epiregulin, Bcl2-like10, PC3B, and retinoblastoma binding protein 7. These 10 genes have expression patterns and postulated functions suggesting that they mediate important processes in the physiology and pathology of ovarian and adrenal tissue.