Inositols: From Established Knowledge to Novel Approaches.
D-chiro-Inositol
FSH
GDM
PCOS
aromatase
epimerase
myo-Inositol
neural tube defects
steroidogenesis
testosterone
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
30 Sep 2021
30 Sep 2021
Historique:
received:
23
07
2021
revised:
13
09
2021
accepted:
22
09
2021
entrez:
13
10
2021
pubmed:
14
10
2021
medline:
3
11
2021
Statut:
epublish
Résumé
Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.
Identifiants
pubmed: 34638926
pii: ijms221910575
doi: 10.3390/ijms221910575
pmc: PMC8508595
pii:
doi:
Substances chimiques
Testosterone
3XMK78S47O
Inositol
4L6452S749
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : G0401315
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0601546
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T003847/1
Pays : United Kingdom
Références
N Engl J Med. 2016 Feb 4;374(5):434-43
pubmed: 26840133
Int J Endocrinol. 2016;2016:1674950
pubmed: 27752262
Int J Endocrinol. 2018 Nov 25;2018:1968450
pubmed: 30595691
Anal Biochem. 1990 Aug 1;188(2):432-5
pubmed: 2221394
Br J Nutr. 2016 Mar 28;115(6):974-83
pubmed: 26847388
Am J Clin Nutr. 2003 Nov;78(5):972-8
pubmed: 14594784
Gynecol Endocrinol. 2019 Aug;35(8):695-700
pubmed: 30880505
Int J Mol Sci. 2017 Oct 20;18(10):
pubmed: 29053604
Int J Bipolar Disord. 2016 Dec;4(1):27
pubmed: 27900734
Subcell Biochem. 2006;39:1-19
pubmed: 17121269
Front Pharmacol. 2020 Mar 26;11:354
pubmed: 32273844
Cytotechnology. 2007 Dec;55(2-3):103-8
pubmed: 19002999
Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9988-92
pubmed: 8234346
Cureus. 2019 Sep 16;11(9):e5671
pubmed: 31720147
J Steroid Biochem Mol Biol. 1997 Apr;61(3-6):281-6
pubmed: 9365202
Trends Endocrinol Metab. 2020 Jun;31(6):435-447
pubmed: 32396844
Isr J Med Sci. 1990 Oct;26(10):541-4
pubmed: 2249926
Eur J Obstet Gynecol Reprod Biol. 2015 Dec;195:72-6
pubmed: 26479434
Am J Epidemiol. 2009 Jan 1;169(1):9-17
pubmed: 18953063
J Clin Endocrinol Metab. 2010 Dec;95(12):E448-55
pubmed: 20926533
Front Endocrinol (Lausanne). 2021 Apr 06;12:660381
pubmed: 33889133
Endocr Connect. 2017 Nov;6(8):647-658
pubmed: 29042448
Med J Aust. 2004 May 3;180(9):462-4
pubmed: 15115425
Am J Case Rep. 2021 Oct 07;22:e932722
pubmed: 34615846
Arch Biochem Biophys. 2003 Sep 15;417(2):251-9
pubmed: 12941308
Antioxidants (Basel). 2021 Aug 13;10(8):
pubmed: 34439531
BMC Pregnancy Childbirth. 2007 Sep 19;7:21
pubmed: 17880716
Am J Obstet Gynecol. 2003 Dec;189(6):1713-9
pubmed: 14710103
Semin Reprod Endocrinol. 1997 May;15(2):111-22
pubmed: 9165656
Gynecol Endocrinol. 2017;33(sup1):8-11
pubmed: 29264980
Expert Opin Drug Metab Toxicol. 2019 Sep;15(9):697-703
pubmed: 31382802
Hum Mol Genet. 2004 Jan 1;13(1):7-14
pubmed: 14613966
Medicine (Baltimore). 2016 Dec;95(52):e5698
pubmed: 28033263
J Med Genet. 2002 Feb;39(2):E5
pubmed: 11836374
Diabetologia. 1990 Oct;33(10):593-6
pubmed: 2257996
Int J Endocrinol. 2017;2017:2549491
pubmed: 28293260
Med Hypotheses. 2016 Jun;91:1-5
pubmed: 27142131
J Clin Endocrinol Metab. 2007 May;92(5):1979-82
pubmed: 17341559
Int J Mol Sci. 2018 Jul 04;19(7):
pubmed: 29973490
J Clin Endocrinol Metab. 2005 Feb;90(2):1171-5
pubmed: 15562012
Steroids. 2012 Jan;77(1-2):27-35
pubmed: 22108547
Genomics. 1995 Jan 20;25(2):507-13
pubmed: 7789985
Endocr J. 2014;61(2):111-7
pubmed: 24189751
Clin Obstet Gynecol. 2003 Jun;46(2):325-40
pubmed: 12808383
Birth Defects Res A Clin Mol Teratol. 2011 Nov;91(11):962-5
pubmed: 21956977
Eur J Obstet Gynecol Reprod Biol. 2018 Sep;228:329-330
pubmed: 29895471
Hum Reprod. 2002 Sep;17(9):2451-8
pubmed: 12202440
Endocrinology. 1991 Dec;129(6):2951-6
pubmed: 1954880
Lancet Diabetes Endocrinol. 2015 Oct;3(10):778-86
pubmed: 26165398
J Neurochem. 1987 May;48(5):1434-42
pubmed: 2435847
Biol Reprod. 2018 Jul 1;99(1):27-44
pubmed: 29438493
J Biol Chem. 1980 Dec 25;255(24):11710-2
pubmed: 7002927
Exp Diabetes Res. 2011;2011:596060
pubmed: 22110473
Eur Rev Med Pharmacol Sci. 2010 Oct;14(10):891-6
pubmed: 21222378
Ann Indian Acad Neurol. 2016 Jul-Sep;19(3):339-43
pubmed: 27570385
J Clin Endocrinol Metab. 2015 Apr;100(4):E572-82
pubmed: 25625804
Int J Mol Sci. 2021 Jun 24;22(13):
pubmed: 34202683
J Clin Endocrinol Metab. 1979 Oct;49(4):514-9
pubmed: 479344
Birth Defects Res. 2017 Jan 30;109(2):68-80
pubmed: 27324558
Adv Nutr. 2021 Feb 1;12(1):212-222
pubmed: 32892218
Int J Gynaecol Obstet. 2021 Apr 2;:
pubmed: 33797759
J Biol Chem. 1992 Mar 25;267(9):6297-301
pubmed: 1372904
Nutrients. 2011 Mar;3(3):370-84
pubmed: 22254102
Annu Rev Neurosci. 2014;37:221-42
pubmed: 25032496
J Assist Reprod Genet. 1992 Dec;9(6):524-30
pubmed: 1299385
Fertil Steril. 2006 Jun;85(6):1761-5
pubmed: 16650422
Gynecol Endocrinol. 2016 Sep;32(9):690-695
pubmed: 27595157
Hum Reprod. 2004 Jan;19(1):41-7
pubmed: 14688154
Nat Rev Dis Primers. 2016 Jun 23;2:16043
pubmed: 27335259
Eur Rev Med Pharmacol Sci. 2007 Sep-Oct;11(5):347-54
pubmed: 18074942
Int J Mol Sci. 2020 Sep 28;21(19):
pubmed: 32998310
Sci Rep. 2021 Apr 23;11(1):8866
pubmed: 33893377
Best Pract Res Clin Obstet Gynaecol. 2018 Jan;46:48-56
pubmed: 29066045
J Biol Chem. 2012 Mar 2;287(10):6991-9
pubmed: 22247557
Mol Genet Metab. 2004 Jun;82(2):154-61
pubmed: 15172003
Gynecol Endocrinol. 2015 Jul;31(7):501-5
pubmed: 26177098
Teratology. 1992 Feb;45(2):223-32
pubmed: 1615432
Drugs. 2000 Aug;60(2):481-516
pubmed: 10983742
Eur Rev Med Pharmacol Sci. 2019 Jun;23(12):5512-5521
pubmed: 31298405
Endocrinology. 2000 Oct;141(10):3852-61
pubmed: 11014242
J Clin Endocrinol Metab. 2009 May;94(5):1752-6
pubmed: 19240151
Epilepsia. 2001 Mar;42(3):295-304
pubmed: 11442143
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Sep 15;879(26):2759-63
pubmed: 21856255
J Cell Physiol. 2019 Jun;234(6):9387-9398
pubmed: 30317628
Eur Rev Med Pharmacol Sci. 2013 Feb;17(4):537-40
pubmed: 23467955
J Assist Reprod Genet. 2015 Mar;32(3):387-94
pubmed: 25601322
N Engl J Med. 1990 Aug 9;323(6):373-8
pubmed: 2370888
Cases J. 2010 Feb 23;3:69
pubmed: 20178574
Hum Reprod Update. 2010 May-Jun;16(3):293-311
pubmed: 19889752
Gynecol Endocrinol. 2015 Feb;31(2):131-5
pubmed: 25259724
Curr Drug Deliv. 2018;15(9):1305-1311
pubmed: 29745333
J Ovarian Res. 2018 May 10;11(1):38
pubmed: 29747700
Biochem Biophys Res Commun. 1986 Nov 14;140(3):974-80
pubmed: 3096334
Clin Res Hepatol Gastroenterol. 2020 Jun;44(3):e45-e49
pubmed: 32146092
Q J Exp Physiol Cogn Med Sci. 1961 Apr;46:188-93
pubmed: 13687775
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2538-42
pubmed: 10051678
Drugs. 1986;32 Suppl 2:6-14
pubmed: 3024950
N Engl J Med. 1999 Apr 29;340(17):1314-20
pubmed: 10219066
Drug Dev Res. 2018 Dec;79(8):373-382
pubmed: 30343496
Sex Med Rev. 2014 Apr;2(2):79-90
pubmed: 27784593
Biochem Biophys Res Commun. 2002 May 10;293(3):1092-8
pubmed: 12051772
Am J Physiol Endocrinol Metab. 2020 Feb 1;318(2):E237-E248
pubmed: 31874063
Eur Rev Med Pharmacol Sci. 2017 Dec;21(23):5491-5498
pubmed: 29243796
Fertil Steril. 2008 Mar;89(3):625-34
pubmed: 17678910
J Clin Endocrinol Metab. 2010 Apr;95(4):1955-61
pubmed: 20133465
Int J Endocrinol. 2016;2016:2839041
pubmed: 27672392
Fertil Steril. 2010 Oct;94(5):1734-8
pubmed: 20004389
Int J Endocrinol. 2020 Mar 27;2020:6461254
pubmed: 32308679
Expert Opin Drug Metab Toxicol. 2020 Mar;16(3):255-274
pubmed: 32129111
Cell Biol Toxicol. 2005 Jan;21(1):1-26
pubmed: 15868485
Basic Clin Androl. 2021 Jun 3;31(1):13
pubmed: 34078260
Trials. 2020 Jul 9;21(1):633
pubmed: 32646482
Expert Opin Drug Metab Toxicol. 2016 Oct;12(10):1181-96
pubmed: 27351907
Proc Natl Acad Sci U S A. 2017 Jun 13;114(24):E4753-E4761
pubmed: 28559354
Diabetes. 1988 Jul;37(7):974-81
pubmed: 3384192
J Clin Endocrinol Metab. 1998 Jun;83(6):2001-5
pubmed: 9626131
Adv Second Messenger Phosphoprotein Res. 1990;24:290-4
pubmed: 2169809
Open Access Maced J Med Sci. 2018 May 13;6(5):803-807
pubmed: 29875849
Ther Adv Endocrinol Metab. 2020 Jul 6;11:2042018820938305
pubmed: 32670541
Nat Med. 1997 Jan;3(1):60-6
pubmed: 8986742
J Endocrinol Invest. 2017 Sep;40(9):899-909
pubmed: 28283913
Int J Endocrinol. 2016;2016:6273298
pubmed: 27777587
Reprod Biol Endocrinol. 2016 Aug 31;14(1):52
pubmed: 27582109
J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59
pubmed: 20525905
N Engl J Med. 1999 Nov 11;341(20):1485-90
pubmed: 10559448
Nature. 2006 Oct 12;443(7112):651-7
pubmed: 17035995
Endocrinology. 1993 Feb;132(2):652-7
pubmed: 8425485
Hum Reprod. 2004 Mar;19(3):510-21
pubmed: 14998944
Eur Rev Med Pharmacol Sci. 2020 Oct;24(19):10143-10154
pubmed: 33090422
Gynecol Endocrinol. 2008 Oct;24(10):562-70
pubmed: 19012099
Am J Epidemiol. 2010 Feb 15;171(4):407-14
pubmed: 20042435
Curr Opin Pediatr. 1994 Aug;6(4):486-91
pubmed: 7951674
Syst Biol Reprod Med. 2021 Feb;67(1):50-63
pubmed: 33094655
Hinyokika Kiyo. 2020 Nov;66(11):407-409
pubmed: 33271659
Epilepsy Res. 2011 Nov;97(1-2):73-82
pubmed: 21820873
Metabolism. 2008 Oct;57(10):1390-7
pubmed: 18803944
Cold Spring Harb Symp Quant Biol. 1988;53 Pt 2:965-71
pubmed: 3076102
Fertil Steril. 2011 Jun 30;95(8):2515-6
pubmed: 21641593
Eur Rev Med Pharmacol Sci. 2019 Mar;23(5):2293-2301
pubmed: 30915778
Expert Opin Drug Metab Toxicol. 2014 Sep;10(9):1193-8
pubmed: 25046730
Expert Opin Drug Metab Toxicol. 2020 Dec;16(12):1187-1198
pubmed: 32966143
Int J Mol Sci. 2021 May 26;22(11):
pubmed: 34073634
J Dairy Sci. 2014 May;97(5):2559-66
pubmed: 24612808
Expert Opin Drug Deliv. 2017 May;14(5):647-655
pubmed: 27552635
Metabolism. 2018 Sep;86:69-78
pubmed: 29530796
Biochim Biophys Acta. 1994 Mar 23;1190(2):469-72
pubmed: 8142451
Gynecol Endocrinol. 2017 Jan;33(1):1-9
pubmed: 27898267
Am J Obstet Gynecol. 2008 Jun;198(6):611-9
pubmed: 18538144
Molecules. 2020 Nov 27;25(23):
pubmed: 33260918
Eur Rev Med Pharmacol Sci. 2021 Apr;25(8):3316-3324
pubmed: 33928619
Eur Rev Med Pharmacol Sci. 2021 Apr;25(7):2843-2851
pubmed: 33877649
Int J Food Sci Nutr. 2021 Aug;72(5):670-679
pubmed: 33238798
Anim Reprod Sci. 2000 Jul 2;60-61:481-92
pubmed: 10844218
Cell Tissue Bank. 2019 Mar;20(1):77-86
pubmed: 30694450
J Clin Med. 2020 May 07;9(5):
pubmed: 32392776
Eur Rev Med Pharmacol Sci. 2011 Aug;15(8):931-6
pubmed: 21845803
J Med Chem. 2003 Jul 17;46(15):3283-91
pubmed: 12852758
Reprod Biol Endocrinol. 2021 Apr 23;19(1):61
pubmed: 33892722
Int J Endocrinol. 2016;2016:3204083
pubmed: 27493664
J Clin Endocrinol Metab. 1979 Apr;48(4):633-8
pubmed: 429508
Reprod Sci. 2014 Feb 4;21(7):854-858
pubmed: 24501149
Mol Cell Endocrinol. 2010 Mar 25;316(2):180-6
pubmed: 19540307
Birth Defects Res A Clin Mol Teratol. 2008 Oct;82(10):728-35
pubmed: 18683893
Int J Womens Health. 2013 Aug 07;5:477-86
pubmed: 23950663
Br J Dermatol. 2004 May;150(5):966-9
pubmed: 15149510
Epidemiology. 2001 Nov;12(6):630-5
pubmed: 11679789
Urology. 2012 Jun;79(6):1290-5
pubmed: 22656408
J Androl. 2004 Mar-Apr;25(2):216-23
pubmed: 14760007
Medicine (Baltimore). 2017 Dec;96(49):e8842
pubmed: 29245250
Gynecol Endocrinol. 2017 Feb;33(2):109-112
pubmed: 27908215
Biochem Soc Trans. 2009 Oct;37(Pt 5):1099-103
pubmed: 19754460
J Obstet Gynaecol Res. 2009 Apr;35(2):282-6
pubmed: 19708174
Lancet. 1991 Jul 20;338(8760):131-7
pubmed: 1677062
Andrology. 2015 May;3(3):491-5
pubmed: 25854593
Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2704-2709
pubmed: 32196621
Expert Opin Drug Deliv. 2012 Mar;9(3):267-71
pubmed: 22339497
Pharmaceuticals (Basel). 2021 May 25;14(6):
pubmed: 34070701
Hum Reprod. 2008 Apr;23(4):783-91
pubmed: 18281682
Eur Rev Med Pharmacol Sci. 2021 Mar;25(5):2383-2389
pubmed: 33755979
Teratology. 1988 Sep;38(3):281-90
pubmed: 3227495
Eur Rev Med Pharmacol Sci. 2021 Jan;25(1):438-446
pubmed: 33506934
Curr Psychiatry Rep. 2015 Aug;17(8):603
pubmed: 26084665
Hum Reprod. 2002 Jun;17(6):1591-6
pubmed: 12042283
Expert Opin Drug Deliv. 2014 Jul;11(7):1103-11
pubmed: 24896369
Arch Gynecol Obstet. 2018 Oct;298(4):675-684
pubmed: 30078122
Eur Rev Med Pharmacol Sci. 2012 May;16(5):575-81
pubmed: 22774396
Diabetes Care. 2021 May;44(5):1091-1099
pubmed: 33782086
Gynecol Endocrinol. 2017 Jul;33(7):524-528
pubmed: 28277112
Int J Exp Diabetes Res. 2002;3(1):47-60
pubmed: 11900279
Expert Opin Drug Metab Toxicol. 2020 Aug;16(8):703-710
pubmed: 32552009
Gynecol Endocrinol. 2016;32(1):65-8
pubmed: 26361940