The role of nuclear receptors in steroid hormone production.
Epidemiological studies implicate steroid hormones as important factors in the development of neoplasia, and hormonal manipulation constitutes an important treatment arm in cancer therapy. Recent studies demonstrate a key role for nuclear receptor proteins in the expression of genes encoding the cytochrome P450 enzymes responsible for steroid hormone biosynthesis. Two orphan nuclear receptors, SF-1 and NGFI-B, regulate steroid hydroxylase transcription; the gene encoding SF-1 is also essential for adrenal and gonadal development. These results highlight the importance of specific nuclear receptors in regulating the enzymes that make essential steroid hormones and in the differentiation of the primary steroidogenic tissues. Ultimately, these nuclear receptors may provide new targets for the design of novel therapies for hormone-dependent cancers.
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
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Parker
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Schimmer
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D018398:Homeodomain Proteins; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D011987:Receptors, Steroid; D013250:Steroid Hydroxylases / Q000235:genetics; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000502:physiology*
D000305:Adrenal Cortex Hormones; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D012739:Gonadal Steroid Hormones; D018398:Homeodomain Proteins; C539821:NR4A1 protein, human; D009687:Nuclear Proteins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D000450:Aldosterone; D013250:Steroid Hydroxylases