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Androgen receptor
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Androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.
The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression; however, the androgen receptor has other functions as well. Androgen-regulated genes are critical for the development and maintenance of the male sexual phenotype.
In some cell types, testosterone interacts directly with androgen receptors, whereas, in others, testosterone is converted by 5-alpha-reductase to dihydrotestosterone (DHT), an even more potent agonist for androgen receptor activation. Testosterone appears to be the primary androgen receptor-activating hormone in the Wolffian duct, whereas dihydrotestosterone is the main androgenic hormone in the urogenital sinus, urogenital tubercle, and hair follicles. Testosterone is therefore responsible primarily for the development of male primary sexual characteristics, whilst dihydrotestosterone is responsible for secondary male characteristics.
Androgens cause slow maturation of the bones, but more of the potent maturation effect comes from the estrogen produced by aromatization of androgens. Steroid users of teen age may find that their growth had been stunted by androgen and/or estrogen excess. People with too little sex hormones can be short during puberty but end up taller as adults as in androgen insensitivity syndrome or estrogen insensitivity syndrome.
Knockout-mice studies have shown that the androgen receptor is essential for normal female fertility, being required for development and full functionality of the ovarian follicles and ovulation, working through both intra-ovarian and neuroendocrine mechanisms.
Via the androgen receptor, androgens play a key role in the maintenance of male skeletal integrity. The regulation of this integrity by androgen receptor (AR) signaling can be attributed to both osteoblasts and osteocytes.
The AR plays a role in regulating female sexual, somatic, and behavioral functions. Experimental data using AR knockout female mice, provides evidence that the promotion of cardiac growth, kidney hypertrophy, cortical bone growth and regulation of trabecular bone structure is a result of DNA-binding-dependent actions of the AR in females.
Moreover, the importance of understanding female androgen receptors lies in their role in several genetic disorders including androgen insensitivity syndrome (AIS). Complete (CAIS) and partial (PAIS) which are a result of mutations in the genes that code for AR. These mutations cause the inactivation of AR due to mutations conferring resistance to circulating testosterone, with more than 400 different AR mutations reported.[citation needed]
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Androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.
The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression; however, the androgen receptor has other functions as well. Androgen-regulated genes are critical for the development and maintenance of the male sexual phenotype.
In some cell types, testosterone interacts directly with androgen receptors, whereas, in others, testosterone is converted by 5-alpha-reductase to dihydrotestosterone (DHT), an even more potent agonist for androgen receptor activation. Testosterone appears to be the primary androgen receptor-activating hormone in the Wolffian duct, whereas dihydrotestosterone is the main androgenic hormone in the urogenital sinus, urogenital tubercle, and hair follicles. Testosterone is therefore responsible primarily for the development of male primary sexual characteristics, whilst dihydrotestosterone is responsible for secondary male characteristics.
Androgens cause slow maturation of the bones, but more of the potent maturation effect comes from the estrogen produced by aromatization of androgens. Steroid users of teen age may find that their growth had been stunted by androgen and/or estrogen excess. People with too little sex hormones can be short during puberty but end up taller as adults as in androgen insensitivity syndrome or estrogen insensitivity syndrome.
Knockout-mice studies have shown that the androgen receptor is essential for normal female fertility, being required for development and full functionality of the ovarian follicles and ovulation, working through both intra-ovarian and neuroendocrine mechanisms.
Via the androgen receptor, androgens play a key role in the maintenance of male skeletal integrity. The regulation of this integrity by androgen receptor (AR) signaling can be attributed to both osteoblasts and osteocytes.
The AR plays a role in regulating female sexual, somatic, and behavioral functions. Experimental data using AR knockout female mice, provides evidence that the promotion of cardiac growth, kidney hypertrophy, cortical bone growth and regulation of trabecular bone structure is a result of DNA-binding-dependent actions of the AR in females.
Moreover, the importance of understanding female androgen receptors lies in their role in several genetic disorders including androgen insensitivity syndrome (AIS). Complete (CAIS) and partial (PAIS) which are a result of mutations in the genes that code for AR. These mutations cause the inactivation of AR due to mutations conferring resistance to circulating testosterone, with more than 400 different AR mutations reported.[citation needed]
