Steroid hormone receptor action. Steroid hormones diffuse across the plasma membrane and associate with a type I or type II nuclear receptor. (a) The type I nuclear receptor (NR), located in the cytoplasm, is complexed with a heat shock protein (Hsp70). Hormone binding releases Hsp70, and the NR dimerizes and exposes a nuclear import signal sequence. The NR-hormone complex then enters the nucleus and binds to a hormone response element (HRE) to activate transcription. (b) Type II nuclear receptors are bound to DNA whether or not the hormone signal is present. For example, the thyroid hormone receptor (TR) forms a heterodimer with the protein RXR to bind the HRE, but it is inactive without thyroid hormone. When the hormone enters the cell and the nucleus and binds the complex at the HRE site, it activates gene transcription.