EXPRESSION AND HORMONAL-REGULATION OF COACTIVATOR AND COREPRESSOR GENES

Steroid/thyroid/retinoid receptors are members of the nuclear receptor superfamily and ligand-inducible transcription factors. These recepto rs modulate transcription of various cellular genes, either positively or negatively, by interacting with specific hormone-response elements located in the target gene promoters. Recent data show that nuclear r eceptors enhance or inhibit transcription by recruiting an array of co activator and corepressor proteins to the transcription complex. We ex amined and compared the expression of four coactivator (steroid recept or coactivator-l and E1A-associated 300-kDa protein) and corepressor ( SMRT and N-CoR) genes in a number of tissues including several endocri ne glands and cell lines. We also addressed whether their messenger RN A levels are hormonally regulated by studying the effects of thyroid h ormone (T-3) and estrogen (E-2) treatment in rat pituitary cells (GH(3 )) in vitro and in anterior pituitary in vivo. Our studies show that t here are distinct tissue-specific expression patterns of these genes. We show that T-3 and E-2 regulate the expression of steroid receptor c oactivator-l messenger RNA in the anterior pituitary in addition to a gender-related difference. These tissue variations may have physiologi cal implications for heterogeneity of hormone responses that are obser ved in normal and malignant tissues.