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

Departments of Pathology (K.H.B., S.O., M.M.M.), Molecular and Human Genetics (K.H.B., M.M.M.), and Molecular and Cellular Biology (M.M.M.), Baylor College of Medicine, Houston, Texas 77030; and Department of Pharmacology, Case Western Reserve University (G.E.O., J.H.N.), Cleveland, Ohio 44106

Address all correspondence and requests for reprints to: Dr. Martin M. Matzuk, Department of Pathology, One Baylor Plaza, Baylor College of Medicine, Houston, Texas 77030. E-mail: mmatzuk{at}bcm.tmc.edu.

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 FSHß and inhibin 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.

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