Tetrahydrodeoxycorticosterone Explained

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]

Chemistry

See also: List of neurosteroids.

See also

Notes and References

  1. Hosie AM, Wilkins ME, da Silva HM, Smart TG . Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites . Nature . 444 . 7118 . 486–9 . November 2006 . 17108970 . 10.1038/nature05324 . 2006Natur.444..486H . 4382394 .
  2. Agís-Balboa RC, Pinna G, Zhubi A, Maloku E, Veldic M, Costa E, Guidotti A . 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 . September 2006 . 16984997 . 1600006 . 10.1073/pnas.0606544103 . 2006PNAS..10314602A . free .
  3. Kokate TG, Svensson BE, Rogawski MA . Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation . The Journal of Pharmacology and Experimental Therapeutics . 270 . 3 . 1223–9 . September 1994 . 7932175 .
  4. Reddy DS, Rogawski MA . Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA(A) receptor function and seizure susceptibility . The Journal of Neuroscience . 22 . 9 . 3795–805 . May 2002 . 11978855 . 6758375 . 10.1523/JNEUROSCI.22-09-03795.2002 .
  5. Reddy DS . Pharmacology of endogenous neuroactive steroids . Critical Reviews in Neurobiology . 15 . 3–4 . 197–234 . 2003 . 15248811 . 10.1615/critrevneurobiol.v15.i34.20 .
  6. Tuveri A, Paoletti AM, Orrù M, Melis GB, Marotto MF, Zedda P, Marrosu F, Sogliano C, Marra C, Biggio G, Concas A . 6 . Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy . Epilepsia . 49 . 7 . 1221–9 . July 2008 . 18325018 . 10.1111/j.1528-1167.2008.01555.x . 23596739 . free .
  7. Reddy DS . Is there a physiological role for the neurosteroid THDOC in stress-sensitive conditions? . Trends in Pharmacological Sciences . 24 . 3 . 103–6 . March 2003 . 12628349 . 10.1016/S0165-6147(03)00023-3 .
  8. Reddy DS . Physiological role of adrenal deoxycorticosterone-derived neuroactive steroids in stress-sensitive conditions . Neuroscience . 138 . 3 . 911–20 . 2006 . 16325348 . 10.1016/j.neuroscience.2005.10.016 . 23576732 .
  9. Eser D, Romeo E, Baghai TC, di Michele F, Schüle C, Pasini A, Zwanzger P, Padberg F, Rupprecht R . 6 . Neuroactive steroids as modulators of depression and anxiety . Neuroscience . 138 . 3 . 1041–8 . 2006 . 16310959 . 10.1016/j.neuroscience.2005.07.007 . 12033307 .
  10. Eser D, Schüle C, Baghai TC, Romeo E, Rupprecht R . Neuroactive steroids in depression and anxiety disorders: clinical studies . Neuroendocrinology . 84 . 4 . 244–54 . 2006 . 17159334 . 10.1159/000097879 . 15711990 .
  11. Maguire J, Mody I . Neurosteroid synthesis-mediated regulation of GABA(A) receptors: relevance to the ovarian cycle and stress . The Journal of Neuroscience . 27 . 9 . 2155–62 . February 2007 . 17329412 . 6673487 . 10.1523/JNEUROSCI.4945-06.2007 .

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