The mechanism of action of steroid hormones: a new twist to an old tale.
Steroid hormones, vitamins, and thyroid hormone are potent chemical messengers that exert dramatic effects on cell differentiation, homeostasis, and morphogenesis. These molecules, though diverse in structure, share a mechanistically similar mode of action. The effector molecules diffuse across cellular membranes and bind to specific high affinity receptors in the target cell nuclei. This interaction results in the conversion of an inactive receptor to one that can interact with the regulatory regions of target genes and modulate the rate of transcription of specific gene sets. The recent cloning and characterization of the functional receptors for these hormones has been enlightening as to the individual steps involved in steroid signal transduction. In addition, emerging evidence suggests that receptor function can be influenced by cell and promoter context indicating that it may be possible to develop tissue specific or tissue-restricted drugs. The concept that a single receptor can modulate gene transcription in a cell-specific manner is of great medical and pharmaceutical importance. The focus of this review is to highlight the recent developments in the steroid receptor field and to illustrate the novel approaches been undertaken to identify novel pharmaceuticals.
McDonnell
D P
DP
Department of Molecular Biology, Ligand Pharmaceuticals, San Diego, California 92121.
Clevenger
B
B
Dana
S
S
Santiso-Mere
D
D
Tzukerman
M T
MT
Gleeson
M A
MA
D000818:Animals; D006801:Humans; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000187:drug effects; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D013256:Steroids