Jump to content

11-Deoxycortisol: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
Line 58: Line 58:


11-Deoxycortisol is synthesized from [[17α-hydroxyprogesterone]] by [[21-hydroxylase]] and is converted to [[cortisol]] by [[11β-hydroxylase]].
11-Deoxycortisol is synthesized from [[17α-hydroxyprogesterone]] by [[21-hydroxylase]] and is converted to [[cortisol]] by [[11β-hydroxylase]].

11-deoxycortisol in mammals has limited biological activity and mostly acts as an intermediate product within glucocorticoid pathway leading to cortisol.
<ref name="merckmanuals">{{cite web |title=Congenital Adrenal Hyperplasia Caused by 11Beta-Hydroxylase Deficiency |url=https://www.merckmanuals.com/professional/pediatrics/endocrine-disorders-in-children/congenital-adrenal-hyperplasia-caused-by-11beta-hydroxylase-deficiency}}</ref> In [[sea lamprey]], a member of the agnathans that evolved more than 500 million years ago, 11-deoxycortisol is the major and final glucocorticoid, with mineralocorticoid activity. Sea lamprey do not have ''CYP11B'' genes hence no [[11β-hydroxylase]] that converts 11-deoxycortisol to cortisol and [[11-deoxycorticosterone]] to [[corticosterone]] in mammals. This indicates that a complex and highly specific corticosteroid signaling pathway evolved at least 500 million years ago with the arrival of the earliest vertebrate.<ref name="pmid32699304">{{cite journal | vauthors = Shaughnessy CA, Barany A, McCormick SD | title = 11-Deoxycortisol controls hydromineral balance in the most basal osmoregulating vertebrate, sea lamprey (Petromyzon marinus) | journal = Scientific Reports | volume = 10 | issue = 1 | pages = 12148 | date = July 2020 | pmid = 32699304 | pmc = 7376053 | doi = 10.1038/s41598-020-69061-4 | url = https://www.nature.com/articles/s41598-020-69061-4}}</ref>


==Clinical significance==
==Clinical significance==

Revision as of 16:50, 3 October 2020

11-Deoxycortisol
Cortodoxone molecule
Names
IUPAC name
(8R,9S,10R,13S,14S,17R)-17-Hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
Other names
11-Deoxycortisol; 11-Deoxycortisone; Cortoxelone; 17α,21-Dihydroxypregn-4-ene-3,20-dione; 17α,21-Dihydroxyprogesterone; 11-Desoxycortisol; 11-Deoxyhydrocortisone; 11-Desoxyhydrocortisone; 17α-Hydroxy-11-deoxycorticosterone; Reichstein's Substance S; Compound S; Cortodoxone; Cortexolone,
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.005.279 Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C21H30O4/c1-19-8-5-14(23)11-13(19)3-4-15-16(19)6-9-20(2)17(15)7-10-21(20,25)18(24)12-22/h11,15-17,22,25H,3-10,12H2,1-2H3/t15-,16+,17+,19+,20+,21+/m1/s1 ☒N
    Key: WHBHBVVOGNECLV-OBQKJFGGSA-N ☒N
  • InChI=1/C21H30O4/c1-19-8-5-14(23)11-13(19)3-4-15-16(19)6-9-20(2)17(15)7-10-21(20,25)18(24)12-22/h11,15-17,22,25H,3-10,12H2,1-2H3/t15-,16+,17+,19+,20+,21+/m1/s1
    Key: WHBHBVVOGNECLV-OBQKJFGGBG
  • O=C4\C=C2/[C@]([C@H]1CC[C@@]3([C@@](O)(C(=O)CO)CC[C@H]3[C@@H]1CC2)C)(C)CC4
Properties
C21H30O4
Molar mass 346.467 g·mol−1
Melting point 215 °C (419 °F; 488 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

11-Deoxycortisol, also known as cortodoxone (INN), as well as 17α,21-dihydroxyprogesterone or 17α,21-dihydroxypregn-4-ene-3,20-dione,[1] is a glucocorticoid steroid hormone. It was first synthesized by Tadeusz Reichstein, and has also been referred to as Reichstein's Substance S[1] or Compound S.[2]

History

On April 5, 1952, biochemist Durey Peterson and microbiologist Herbert Murray at Upjohn published the first report of a breakthrough fermentation process for the microbial 11α-oxygenation of steroids (e.g. progesterone) in a single step by common molds of the order Mucorales.[3] 11α-oxygenation of Compound S produces 11α-hydrocortisone, which can be chemically oxidized to cortisone, or converted by further chemical steps to 11β-hydrocortisone (cortisol).

Function

11-Deoxycortisol acts as a glucocorticoid, though is less potent than cortisol.[4]

11-Deoxycortisol is synthesized from 17α-hydroxyprogesterone by 21-hydroxylase and is converted to cortisol by 11β-hydroxylase.

11-deoxycortisol in mammals has limited biological activity and mostly acts as an intermediate product within glucocorticoid pathway leading to cortisol. [5] In sea lamprey, a member of the agnathans that evolved more than 500 million years ago, 11-deoxycortisol is the major and final glucocorticoid, with mineralocorticoid activity. Sea lamprey do not have CYP11B genes hence no 11β-hydroxylase that converts 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone in mammals. This indicates that a complex and highly specific corticosteroid signaling pathway evolved at least 500 million years ago with the arrival of the earliest vertebrate.[6]

Clinical significance

In 11β-hydroxylase deficiency, 11-deoxycortisol and 11-deoxycorticosterone levels increase, and excess of 11-deoxycorticosterone leads to mineralocorticoid-based hypertension[7] (as opposed to 21-hydroxylase deficiency, in which patients have low blood pressure from a lack of mineralocorticoids[dubious – discuss][medical citation needed]). In 11β-hydroxylase deficiency, 11-deoxycortisol can also be converted to androstenedione in a pathway that could explain the increase in androstenedione levels this condition.[8]

In 21-hydroxylase deficiency, 11-deoxycortisol levels are low.[9]

See also

References

  1. ^ a b R.A. Hill; H.L.J. Makin; D.N. Kirk; G.M. Murphy (23 May 1991). Dictionary of Steroids. CRC Press. pp. 338–. ISBN 978-0-412-27060-4.
  2. ^ Wudy SA, Hartmann M, Homoki J (September 2002). "Determination of 11-deoxycortisol (Reichstein's compound S) in human plasma by clinical isotope dilution mass spectrometry using benchtop gas chromatography-mass selective detection". Steroids. 67 (10): 851–7. doi:10.1016/s0039-128x(02)00052-1. PMID 12231120.
  3. ^ Peterson DH; Murray, HC (1952). "Microbiological oxygenation of steroids at carbon 11". J Am Chem Soc. 74 (7): 1871–2. doi:10.1021/ja01127a531.
  4. ^ Engels M, Pijnenburg-Kleizen KJ, Utari A, Faradz SM, Oude-Alink S, van Herwaarden AE, Span PN, Sweep FC, Claahsen-van der Grinten HL (November 2019). "Glucocorticoid Activity of Adrenal Steroid Precursors in Untreated Patients With Congenital Adrenal Hyperplasia". The Journal of Clinical Endocrinology and Metabolism. 104 (11): 5065–5072. doi:10.1210/jc.2019-00547. PMID 31090904.
  5. ^ "Congenital Adrenal Hyperplasia Caused by 11Beta-Hydroxylase Deficiency".
  6. ^ Shaughnessy CA, Barany A, McCormick SD (July 2020). "11-Deoxycortisol controls hydromineral balance in the most basal osmoregulating vertebrate, sea lamprey (Petromyzon marinus)". Scientific Reports. 10 (1): 12148. doi:10.1038/s41598-020-69061-4. PMC 7376053. PMID 32699304.
  7. ^ Gupta V (October 2011). "Mineralocorticoid hypertension". Indian Journal of Endocrinology and Metabolism. 15 Suppl 4: S298–312. doi:10.4103/2230-8210.86972. PMC 3230101. PMID 22145132.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ Auzéby A, Bogdan A, Touitou Y (January 1991). "Evidence for a new biologic pathway of androstenedione synthesis from 11-deoxycortisol". Steroids. 56 (1): 33–6. doi:10.1016/0039-128X(91)90112-9. PMID 2028480. S2CID 6261965.
  9. ^ C.R. Kannan (2013). Essential Endocrinology: A Primer for Nonspecialists. Springer Science & Business Media. p. 263. ISBN 9781489916921.
Retrieved from "https://en.wikipedia.org/w/index.php?title=11-Deoxycortisol&oldid=981651768"