ABSTRACT
Steroid Hormone Action Unlike catecholamine and polypeptide hormones, steroids, which are lipophilic, are transported in plasma bound to carrier proteins (produced by the liver), and act in their target cells by either increasing or decreasing synthesis of specific proteins (e.g., enzymes). Steroids enter virtually all cells of the body, but bind only to specific receptor proteins in the cytoplasm and/or nucleus of target cells (i.e., gluco-and mineralocorticoid receptors are thought to be located in the cytoplasm, while 1,25(OH)2D (a secosteroid), retinoic acid and sex steroid receptors are in the nucleus). In Part B, process 1 shows a steroid hormone dissociating from a plasma transport protein and entering a target cell via diffusion through the lipid bilayer. Within the cytoplasm, unbound steroid receptors contain heat shock protein (HSP), which if translocated to the nucleus would mask the receptor DNA-binding domain. Binding of the cytoplasmic steroidal ligand with its receptor (process 2) promotes a conformational change (i.e.,”activation”) in the receptor protein itself (process 3), resulting in the release of HSP. The ligandreceptor complex translocates to the nucleus (process 4), binding to DNA (process 8). Some steroid hormones bypass processes 2-4, moving directly into the nucleus (process 5), where they bind to nuclear receptors (process 6), thus activating/inactivating them (process 7). Once activated ligand-receptor complexes have bound to specific hormone response elements (HREs; process 8), they function as regulators of gene transcription (process 9). New mRNAs are translocated to the cytoplasm (process 10) and assembled into translational complexes for the synthesis of proteins (process 11) that alter target cell function (process 12). Note that in some instances steroid receptor complexes actually repress, rather than induce, specific gene transcription.
