Intro to Pharmacology and Toxicology
Topics
Despite the different physiological effects produced by steroid hormones in different cells and tissues, these hormones have a common mechanism of action at the molecular level. They all bind to receptors and allow them to activate transcription from a limited number of genes.
After
diffusing across the plasma membrane, the steroid binds to its receptor which
may be located in the cytoplasm or in the nucleus. Binding of steroid promotes
transformation of the receptor into a state that moves into a high affinity
nuclear complex at the site of the appropriate hormone response element in DNA,
where it enhances transcription of neighboring genes regulated by that element
Steroid hormone response elements (HREs) are discrete genomic regions upstream (5') of the transcriptional start site of inducible genes. These regulatory elements contain 13 to 15 base pairs arranged in a consensus sequence of palindromic manner that is specific for a specific receptor to bind as a dimer.
Steroid hormones receptors are located in the cytoplasm or nucleus and exist as heteroprotein complexes with a regulatory domain. They bind to HREs in the nucleus and stimulate transcription upon binding by steroid hormone. They all have a zinc-finger DNA-binding domain, a hormone-binding domain and an activation domain. When bound to hormone, the regulatory domain is released, exposing the DNA binding domain
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