Steroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [1-2,4]) 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 hsp90β (HSP90AB1, P08238) and immunophilin FKBP52:FKBP4, Q02790), which are shed on binding the steroid hormone. Although rapid signalling phenomena are observed [3,6], 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 [8].

A 7TM receptor responsive to estrogen (GPER1, Q99527, also known as GPR30, see [5]) has been described. Human orthologues of 7TM 'membrane progestin receptors' (PAQR7, PAQR8 and PAQR5), initially discovered in fish [9-10], appear to localize to intracellular membranes and respond to 'non-genomic' progesterone analogues independently of G proteins [7].

* Key recommended reading is highlighted with an asterisk

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Briet M, Schiffrin EL. (2010) Aldosterone: effects on the kidney and cardiovascular system. Nat Rev Nephrol, 6 (5): 261-73. [PMID:20234356]

Brinton RD. (2009) Estrogen-induced plasticity from cells to circuits: predictions for cognitive function. Trends Pharmacol Sci, 30 (4): 212-22. [PMID:19299024]

Callewaert F, Boonen S, Vanderschueren D. (2010) Sex steroids and the male skeleton: a tale of two hormones. Trends Endocrinol Metab, 21 (2): 89-95. [PMID:19837603]

Chen Y, Sawyers CL, Scher HI. (2008) Targeting the androgen receptor pathway in prostate cancer. Curr Opin Pharmacol, 8 (4): 440-8. [PMID:18674639]

Dahlman-Wright K, Cavailles V, Fuqua SA, Jordan VC, Katzenellenbogen JA, Korach KS, Maggi A, Muramatsu M, Parker MG, Gustafsson JA. (2006) International Union of Pharmacology. LXIV. Estrogen receptors. Pharmacol Rev, 58 (4): 773-81. [PMID:17132854]

Feldman RD, Gros R. (2011) Unraveling the mechanisms underlying the rapid vascular effects of steroids: sorting out the receptors and the pathways. Br J Pharmacol, 163 (6): 1163-9. [PMID:21545416]

Gross KL, Cidlowski JA. (2008) Tissue-specific glucocorticoid action: a family affair. Trends Endocrinol Metab, 19 (9): 331-9. [PMID:18805703]

Hadoke PW, Iqbal J, Walker BR. (2009) Therapeutic manipulation of glucocorticoid metabolism in cardiovascular disease. Br J Pharmacol, 156 (5): 689-712. [PMID:19239478]

Handelsman DJ. (2008) Indirect androgen doping by oestrogen blockade in sports. Br J Pharmacol, 154 (3): 598-605. [PMID:18500381]

Joëls M, Karst H, DeRijk R, de Kloet ER. (2008) The coming out of the brain mineralocorticoid receptor. Trends Neurosci, 31 (1): 1-7. [PMID:18063498]

Kellner M, Wiedemann K. (2008) Mineralocorticoid receptors in brain, in health and disease: possibilities for new pharmacotherapy. Eur J Pharmacol, 583 (2-3): 372-8. [PMID:18272147]

Kerkhofs S, Denayer S, Haelens A, Claessens F. (2009) Androgen receptor knockout and knock-in mouse models. J Mol Endocrinol, 42 (1): 11-7. [PMID:18923000]

Lange CA, Gioeli D, Hammes SR, Marker PC. (2007) Integration of rapid signaling events with steroid hormone receptor action in breast and prostate cancer. Annu Rev Physiol, 69: 171-99. [PMID:17037979]

Levin ER. (2008) Rapid signaling by steroid receptors. Am J Physiol Regul Integr Comp Physiol, 295 (5): R1425-30. [PMID:18784332]

Lu NZ, Wardell SE, Burnstein KL, Defranco D, Fuller PJ, Giguere V, Hochberg RB, McKay L, Renoir JM, Weigel NL, Wilson EM, McDonnell DP, Cidlowski JA. (2006) International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. Pharmacol Rev, 58 (4): 782-97. [PMID:17132855]

Matsumoto T, Shiina H, Kawano H, Sato T, Kato S. (2008) Androgen receptor functions in male and female physiology. J Steroid Biochem Mol Biol, 109 (3-5): 236-41. [PMID:18434134]

Mohler ML, Bohl CE, Jones A, Coss CC, Narayanan R, He Y, Hwang DJ, Dalton JT, Miller DD. (2009) Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit. J Med Chem, 52 (12): 3597-617. [PMID:19432422]

Pippal JB, Fuller PJ. (2008) Structure-function relationships in the mineralocorticoid receptor. J Mol Endocrinol, 41 (6): 405-13. [PMID:18805937]

Prossnitz ER, Arterburn JB, Smith HO, Oprea TI, Sklar LA, Hathaway HJ. (2008) Estrogen signaling through the transmembrane G protein-coupled receptor GPR30. Annu Rev Physiol, 70: 165-90. [PMID:18271749]

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]

Simons SS. (2010) Glucocorticoid receptor cofactors as therapeutic targets. Curr Opin Pharmacol, 10 (6): 613-9. [PMID:20801081]

Taplin ME. (2007) Drug insight: role of the androgen receptor in the development and progression of prostate cancer. Nat Clin Pract Oncol, 4 (4): 236-44. [PMID:17392714]

Weiser MJ, Foradori CD, Handa RJ. (2008) Estrogen receptor beta in the brain: from form to function. Brain Res Rev, 57 (2): 309-20. [PMID:17662459]

Woolley CS. (2007) Acute effects of estrogen on neuronal physiology. Annu Rev Pharmacol Toxicol, 47: 657-80. [PMID:16918306]

1. Alexander SPH, Cidlowski JA, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ et al.. (2019) THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Nuclear hormone receptors. Br J Pharmacol, 176 Suppl 1: S229-S246. [PMID:31710718]

2. Dahlman-Wright K, Cavailles V, Fuqua SA, Jordan VC, Katzenellenbogen JA, Korach KS, Maggi A, Muramatsu M, Parker MG, Gustafsson JA. (2006) International Union of Pharmacology. LXIV. Estrogen receptors. Pharmacol Rev, 58 (4): 773-81. [PMID:17132854]

3. Levin ER. (2008) Rapid signaling by steroid receptors. Am J Physiol Regul Integr Comp Physiol, 295 (5): R1425-30. [PMID:18784332]

4. Lu NZ, Wardell SE, Burnstein KL, Defranco D, Fuller PJ, Giguere V, Hochberg RB, McKay L, Renoir JM, Weigel NL, Wilson EM, McDonnell DP, Cidlowski JA. (2006) International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. Pharmacol Rev, 58 (4): 782-97. [PMID:17132855]

5. Prossnitz ER, Arterburn JB, Smith HO, Oprea TI, Sklar LA, Hathaway HJ. (2008) Estrogen signaling through the transmembrane G protein-coupled receptor GPR30. Annu Rev Physiol, 70: 165-90. [PMID:18271749]

6. Prossnitz ER, Maggiolini M. (2009) Non-genomic signaling by steroids. Mol Cell Endocrinol, 308 (1-2): 1-2. [PMID:19389460]

7. Smith JL, Kupchak BR, Garitaonandia I, Hoang LK, Maina AS, Regalla LM, Lyons TJ. (2008) Heterologous expression of human mPRalpha, mPRbeta and mPRgamma in yeast confirms their ability to function as membrane progesterone receptors. Steroids, 73 (11): 1160-73. [PMID:18603275]

8. Vegeto E, Shahbaz MM, Wen DX, Goldman ME, O'Malley BW, McDonnell DP. (1993) Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function. Mol Endocrinol, 7 (10): 1244-55. [PMID:8264658]

9. Zhu Y, Bond J, Thomas P. (2003) Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor. Proc Natl Acad Sci USA, 100 (5): 2237-42. [PMID:12601167]

10. Zhu Y, Rice CD, Pang Y, Pace M, Thomas P. (2003) Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes. Proc Natl Acad Sci USA, 100 (5): 2231-6. [PMID:12574519]