Molecular pathways of steroid receptor action.

Over the past two decades, a great deal of evidence has accumulated in favor of the hypothesis that steroid hormones act at the level of nuclear DNA to regulate gene expression (Jensen EV, Suzuki T, Kawashima T, Stumpf WE, Jungblut PW, DeSombre ER, Proc Natl Acad Sci USA 1968; 59:632-638; Gorski J, Toft D, Shyamala G, Smith D, Notides A, Rec Prog Horm Res 1968; 24:45-80; O'Malley BW, Means AR, Science 1974; 183:610-620; O'Malley BW, Roop DR, Lai EC, Nordstrom JL, Catterall JF, Swaneck GE, Colbert DA, Tsai M-J, Dugaiczyk A, Woo SLC, Rec Prog Horm Res 1979; 35:1-46). The earliest studies were qualitative and involved experiments showing that steroid hormones (1) cause accumulation of new species of hybridizable RNAs that did not exist prior to stimulation; (2) cause stimulation of synthesis of new specific proteins; (3) cause a corresponding increase in the cellular levels of specific mRNAs; and (4) stimulate the rate of transcription of certain nuclear genes (O'Malley BW, McGuire WL, Kohler PO, Korenman SG, Rec Prog Horm Res 1969; 25:105-000). At that time, the early 1970s, the primary pathway for steroid hormone action was defined as follows: steroid----(steroid-receptor)----(steroid-receptor-DNA)----mRNA----fu nct ional response (O'Malley BW, Roop DR, Lai EC, Nordstrom JL, Catterall JF, Swaneck GE, Colbert DA, Tsai M-J, Dugaiczyk A, Woo SLC, Rec Prog Horm Res 1979; 35:1-46. Steroid enters cells by passive diffusion and allosterically activates receptors in either the cytoplasm or nucleus. The activated receptor binds usually at the 5'-flanking region of target genes and stimulates transcription and protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)