Chemical compound
Tetrahydrodeoxycorticosterone (abbreviated as THDOC ; 3α,21-dihydroxy-5α-pregnan-20-one), also referred to as allotetrahydrocorticosterone , is an endogenous neurosteroid .[ 1] It is synthesized from the adrenal hormone deoxycorticosterone by the action of two enzymes, 5α-reductase type I and 3α-hydroxysteroid dehydrogenase .[ 2] THDOC is a potent positive allosteric modulator of the GABAA receptor , and has sedative , anxiolytic and anticonvulsant effects.[ 3] [ 4] [ 5] Changes in the normal levels of this steroid particularly during pregnancy and menstruation may be involved in some types of epilepsy (catamenial epilepsy ) and premenstrual syndrome ,[ 6] as well as stress , anxiety and depression .[ 7] [ 8] [ 9] [ 10] [ 11]
^ Hosie AM, Wilkins ME, da Silva HM, Smart TG (November 2006). "Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites". Nature . 444 (7118): 486–9. Bibcode :2006Natur.444..486H . doi :10.1038/nature05324 . PMID 17108970 . S2CID 4382394 .
^ Agís-Balboa RC, Pinna G, Zhubi A, Maloku E, Veldic M, Costa E, Guidotti A (September 2006). "Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis" . Proceedings of the National Academy of Sciences of the United States of America . 103 (39): 14602–7. Bibcode :2006PNAS..10314602A . doi :10.1073/pnas.0606544103 . PMC 1600006 . PMID 16984997 .
^ Kokate TG, Svensson BE, Rogawski MA (September 1994). "Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation". The Journal of Pharmacology and Experimental Therapeutics . 270 (3): 1223–9. PMID 7932175 .
^ Reddy DS, Rogawski MA (May 2002). "Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA(A) receptor function and seizure susceptibility" . The Journal of Neuroscience . 22 (9): 3795–805. doi :10.1523/JNEUROSCI.22-09-03795.2002 . PMC 6758375 . PMID 11978855 .
^ Reddy DS (2003). "Pharmacology of endogenous neuroactive steroids". Critical Reviews in Neurobiology . 15 (3–4): 197–234. doi :10.1615/critrevneurobiol.v15.i34.20 . PMID 15248811 .
^ Tuveri A, Paoletti AM, Orrù M, Melis GB, Marotto MF, Zedda P, et al. (July 2008). "Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy" . Epilepsia . 49 (7): 1221–9. doi :10.1111/j.1528-1167.2008.01555.x . PMID 18325018 . S2CID 23596739 .
^ Reddy DS (March 2003). "Is there a physiological role for the neurosteroid THDOC in stress-sensitive conditions?". Trends in Pharmacological Sciences . 24 (3): 103–6. doi :10.1016/S0165-6147(03)00023-3 . PMID 12628349 .
^ Reddy DS (2006). "Physiological role of adrenal deoxycorticosterone-derived neuroactive steroids in stress-sensitive conditions". Neuroscience . 138 (3): 911–20. doi :10.1016/j.neuroscience.2005.10.016 . PMID 16325348 . S2CID 23576732 .
^ Eser D, Romeo E, Baghai TC, di Michele F, Schüle C, Pasini A, et al. (2006). "Neuroactive steroids as modulators of depression and anxiety". Neuroscience . 138 (3): 1041–8. doi :10.1016/j.neuroscience.2005.07.007 . PMID 16310959 . S2CID 12033307 .
^ Eser D, Schüle C, Baghai TC, Romeo E, Rupprecht R (2006). "Neuroactive steroids in depression and anxiety disorders: clinical studies" (PDF) . Neuroendocrinology . 84 (4): 244–54. doi :10.1159/000097879 . PMID 17159334 . S2CID 15711990 .
^ Maguire J, Mody I (February 2007). "Neurosteroid synthesis-mediated regulation of GABA(A) receptors: relevance to the ovarian cycle and stress" . The Journal of Neuroscience . 27 (9): 2155–62. doi :10.1523/JNEUROSCI.4945-06.2007 . PMC 6673487 . PMID 17329412 .