Steroid hormone receptors (nomenclature as agreed by NC-IUPHAR Committee on Nuclear Receptors, [2,11]) are nuclear hormone receptors of the NR3 class, with endogenous agonists that may be divided into 3-hydroxysteroids (estrone and 17β-estradiol) and 3-ketosteroids (dihydrotestosterone [DHT], aldosterone, cortisol, corticosterone, progesterone and testosterone). These receptors exist as dimers coupled with chaperone molecules (such as hsp90 [ENSG00000166598] and immunophilin FKBP52 [ENSG00000004478]), which are shed on binding the steroid hormone. Although rapid signalling phenomena are observed [10,17], the principal signalling cascade appears to involve binding of the activated receptors to nuclear hormone response elements of the genome, with a 15-nucleotide consensus sequence AGAACAnnnTGTTCT (i.e. an inverted palindrome) as homo- or heterodimers. They also affect transcription by protein–protein interactions with other transcription factors, such as activator protein 1 (AP-1) and nuclear factor κB (NF-κB). Splice variants of each of these receptors can form functional or non-functional monomers that can dimerize to form functional or non-functional receptors. For example, alternative splicing of PR mRNA produces A and B monomers that combine to produce functional AA, AB and BB receptors with distinct characteristics [26].
A 7TM receptor responsive to estrogen (GPER, also known as GPR30, ENSG00000164850, see [16]) has been described. Human orthologues of 7TM ‘membrane progestin receptors’ (ENSG00000182749, ENSG00000170915 and ENSG00000137819), initially discovered in fish [29-30], appear to localize to intracellular membranes and respond to ‘non-genomic’ progesterone analogues independently of G proteins [20].
3C. 3-Ketosteroid receptors
More information on this family may be found on the IUPHAR-DB family and introduction pages.
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
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Progesterone receptor Show »« Hide
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[3H]dexamethasone also binds to MR in vitro. PR antagonists have been suggested to subdivide into Type I (e.g. onapristone) and Type II (e.g. ZK112993) groups. These groups appear to promote binding of PR to DNA with different efficacies and evoke distinct conformational changes in the receptor, leading to a transcription-neutral complex [3,9]. Mutations in AR underlie testicular feminization and androgen insensibility syndromes, spinal and bulbar muscular atrophy (Kennedy's disease).
3A. Estrogen receptors
More information on this family may be found on the IUPHAR-DB family and introduction pages.
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors
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Estrogen receptor-α Show »« Hide
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Estrogen receptor-β Show »« Hide
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R,R-THC exhibits partial agonist activity at ERα [13,24]. Estrogen receptors may be blocked non-selectively by tamoxifen and raloxifene and labelled by [3H]17β-estradiol and [3H]tamoxifen. Many agents thought initially to be antagonists at estrogen receptors appear to have tissue-specific efficacy (e.g. tamoxifen is an antagonist at estrogen receptors in the breast, but is an agonist at estrogen receptors in the uterus), hence the descriptor SERM (selective estrogen receptor modulator) or SnuRM (selective nuclear receptor modulator). Y134 has been suggested to be an ERα-selective estrogen receptor modulator [15].
Additional ‘orphan’ estrogen receptor-related proteins have been described (ERRα ENSG00000173153; ERRβ ENSG00000119715; ERRγ ENSG00000196482; DY131 is an agonist with selectivity for ERRβ and ERRγ compared with ERRα, ERα and ERβ [28].
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Schumacher, M; Sitruk-Ware, R; De Nicola, AF. (2008) Progesterone and progestins: neuroprotection and myelin repair. Curr Opin Pharmacol, 8 (6): 740-6. [PMID:18929681]
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