Gene expression profiling of the effects of castration and estrogen treatment in the rat uterus.
The development and functions of female reproductive tissues are regulated by the actions of two major sex steroid hormones, estrogen and progesterone. To investigate estrogen-dependent gene expression in the rat uterus, we studied the effect of ovariectomy with or without estrogen treatment on the uterine expression of 3000 genes using cDNA microarrays. Many genes were regulated by either treatment, but only few were reciprocally regulated by these contrasting treatments. The present study confirms previous findings and identifies several genes with expressions not previously known to be influenced by estrogen. These genes include follistatin-related protein, Thy-1 glycoprotein, alpha-fodrin, CD24, immediate early response 5, insulin-like growth factor-binding protein 2, growth response protein CL-6 (INSIG-1), ladinin1, class I major histocompatibility complex heavy chain, lactadherin, ezrin, and Fas-activated serine/threonine kinase. Because of their function as regulators of proliferation and apoptosis, CD24, insulin-like growth factor-binding protein 2, and Fas/Fas ligand were examined further by immunohistochemical expression and tissue localization analysis. Our analysis confirms a contrasting regulation of these gene products by ovariectomy and estrogen treatment. The present study identifies novel mediators of estrogen actions in the uterus and provides genome-wide expression data from which novel hypotheses regarding uterine function can be generated.
Wu
Xuxia
X
Department of Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
Pang
See-Tong
ST
Sahlin
Lena
L
Blanck
Agneta
A
Norstedt
Gunnar
G
Flores-Morales
Amilcar
A
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051927:CD24 Antigen; D002352:Carrier Proteins / Q000235:genetics; D003598:Cytoskeletal Proteins; D004958:Estradiol / Q000494:pharmacology*; D053222:Fas Ligand Protein; D005260:Female; D038702:Follistatin-Related Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry / Q000379:methods; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D008840:Microfilament Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010052:Ovariectomy / Q000009:adverse effects*; D010750:Phosphoproteins / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D013049:Spectrin; D000099149:Ezrin
D015703:Antigens, CD; D051927:CD24 Antigen; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004958:Estradiol; D053222:Fas Ligand Protein; D038702:Follistatin-Related Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D013049:Spectrin; D000099149:Ezrin; C505662:Faslg protein, rat; C491574:Insig1 protein, rat