An Alternative Ligand-Independent Pathway for Activation of Steroid Receptors

Publisher Summary Classical steroid hormones such as estrogens, progestins, androgens, glucocorticoids, and mineralocorticoids act via binding to specific intracellular receptors. These receptors are DNA-binding transcription factors, which, in turn, regulate the amount of mRNA transcripts emanating from target genes. The cognate aporeceptors for steroid hormones are usually found in a complex with heat shock proteins before ligand-dependent activation. Ligand binds and induces an allosteric conformational change in the receptor, which causes heat shock proteins to be shed, and facilitates dimerization of the receptors. Pharmacologic inhibition of cellular phosphatases could enhance ligand-dependent activation of the chicken progesterone receptor (cPR). Also, inhibition of cellular kinases can dampen ligand-dependent activation of cPR. The steroid receptor pathway can be activated alternatively from the membrane via pathway convergence, but the average cell responses are likely to be more complicated.