The steroid receptors contain a highly conserved DNA-binding domain, a moderately conserved ligand-binding domain, and less well-conserved amino- and carboxy-terminal domains. The structure of the steroid receptors is modular, with distinct domains. The steroid hormone receptors belong to a large family of transcription factors called nuclear receptors. Mechanistic studies have built on the classic mode of action to reveal a complex regulatory network of interacting factors and chromatin state.Įvolution of Steroid Hormone Receptor Structure and Function The hormone-dependent changes in receptor conformation drive transactivation and transrepression of gene expression by altering interactions with molecular chaperones that keep the receptor in a ligand-independent state, inducing posttranslational modifications of the receptor that alter activity, promoting the formation of receptor dimers, enhancing interactions with specific DNA sequences (hormone response element), and facilitating recruitment of coactivator or corepressor proteins that alter chromatin structure and contact the basal transcription machinery. The classic mode of action entails simple diffusion of steroid hormones into the cell, where they interact with cognate receptors and stimulate or inhibit transcription of target genes ( Fig. This chapter reviews what is known about the mechanisms of steroid action. Moreover, it is also necessary to define the unique mechanisms that lead to hormone-specific effects and functions, which also occur in a cell-specific manner. Consequently, a clear and complete understanding of the basic mechanisms of steroid hormone action is of critical importance for health and disease. These hormones control diverse physiologic and cellular processes and affect almost all aspects of eukaryotic physiology, from sexual differentiation, growth, and reproduction to immunity, metabolism, and behavior. Despite their shared molecular origin and basic structural similarities, mineralocorticoids, glucocorticoids, estrogens, progestins, and androgens are distinct classes of steroid hormones that interact with specific, high-affinity receptors to exert their biological effects (mineralocorticoid receptor, glucocorticoid receptor, estrogen receptor, progestin receptor, and androgen receptor ). Within the adrenal cortex, mineralocorticoids and glucocorticoids are produced, while the sex steroids ( estrogens, progestins, and androgens ) are primarily generated by the gonads. Essential for life, the adrenal gland is the most important steroidogenic organ in the human body. Steroids are small, lipophilic hormones synthesized from a common precursor molecule, cholesterol, through a complex biosynthetic process in tissues and glands throughout the body (see Chapter 4 ). Precise regulation of gene transcription is essential for development, physiology, and homeostasis. Steroid hormones exert their functions by diffusing through the cell membrane, binding their receptors, inducing a conformational change in the receptor, associating with DNA, interacting with cofactors, and altering gene expression. Steroid hormones are metabolites of cholesterol that bind to intracellular receptors with high specificity. Steroid Hormone Receptors Act as Ligand-Dependent Transcription Factors or Repressors
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