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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]
Chemistry
See also
References
^ 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 .
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