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This version published online on June 26, 2003
Endocrinology, doi:10.1210/en.2003-0476
A more recent version of this article appeared on October 1, 2003
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Submitted on April 16, 2003
Accepted on June 17, 2003

Expression profiling analyses of gonadotropin responses and tumor development in the absence of inhibins

Kathleen H. Burns1, Gabe E. Owens1, Samuel C. Ogbonna1, John H. Nilson1, and Martin M. Matzuk1*

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

* To whom correspondence should be addressed. E-mail: mmatzuk{at}bcm.tmc.edu.

Transgenic mice with engineered disruptions in the bidirectional endocrine signaling between the pituitary and gonad have shed light on specific effects of the loss-of-function of gonadotropins and inhibins. These models are valuable tools for studying ovarian biology as 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 FSH{beta} and inhibin {alpha} 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, VCAM, epiregulin, Bcl2-like10, PC3B, and retinoblastoma binding protein 7. These 10 genes have expression patterns and postulated functions which suggest that they mediate important processes in the physiology and pathology of ovarian and adrenal tissue.


Key words: Affymetrix® GeneChip • folliculogenesis • ovarian cancer • adrenal cortex • tumor







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