17α-Hydroxypregnenolone: Difference between revisions

17α-Hydroxypregnenolone
Pharmacokinetic data
Metabolism	Adrenal, Gonads
Identifiers
	IUPAC name 3β,17α-dihydroxypregn-5-en-20-one;
CAS Number	387-79-1 ;
PubChem CID	3032570;
ChemSpider	17215939 ;
UNII	77ME40334S;
ChEBI	CHEBI:28750 ;
CompTox Dashboard (EPA)	DTXSID20894988 ;
ECHA InfoCard	100.006.239
Chemical and physical data
Formula	C21H32O3
Molar mass	332.484 g·mol−1
3D model (JSmol)	Interactive image;
Melting point	268 °C (514 °F)
	SMILES CC[C@@]2(O)CC[C@H]1[C@@H]3CCC4CC(O)C(=O)C[C@]4(C)[C@H]3CC[C@@]12C;
	InChI InChI=1S/C21H34O3/c1-4-21(24)10-8-16-14-6-5-13-11-17(22)18(23)12-19(13,2)15(14)7-9-20(16,21)3/h13-17,22,24H,4-12H2,1-3H3/t13?,14-,15+,16+,17?,19+,20+,21-/m1/s1 ; Key:QPLFSAZMHUAMKE-FOCOMJRBSA-N ;
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17α-Hydroxypregnenolone is a pregnane (C21) steroid that is obtained by hydroxylation of pregnenolone at the C17α position. This step is performed by the mitochondrial cytochrome P450 enzyme 17α-hydroxylase (CYP17A1) that is present in the adrenal and gonads. Peak levels are reached in humans at the end of puberty and then decline.^[1] High levels are also achieved during pregnancy. It is also a known neuromodulator.

Prohormone

17α-Hydroxypregnenolone is considered a prohormone in the formation of dehydroepiandrosterone (DHEA), itself a prohormone of the sex steroids.

This conversion is mediated by the enzyme 17,20 lyase. As such 17α-hydroxypregenolone represents an intermediary in the Δ⁵ pathway that leads from pregnenolone to DHEA. 17α-Hydroxypregneolone is also converted to 17α-hydroxyprogesterone, a prohormone for glucocorticosteroids and androstenedione through the activity of 3α-hydroxysteroid dehydrogenase.

Clinical use

Measurements of 17α-hydroxypregnenolone are useful in the diagnosis of certain forms of congenital adrenal hyperplasia.^[2] In patients with congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency 17α-hydroxypregnenolone is increased, while in patients with congenital adrenal hyperplasia due to 17α-hydroxylase deficiency levels are low to absent.

Neurosteroid

17α-hydroxypregnenolone is a known neuromodulator as its acts in the central nervous system. Specifically, it is known to modulate locomotion.^[3]

Additional images

Steroidogenesis

References

^ Hill M, Lukác D, Lapcík O, Sulcová J, Hampl R, Pouzar V, Stárka L (April 1999). "Age relationships and sex differences in serum levels of pregnenolone and 17-hydroxypregnenolone in healthy subjects". Clinical Chemistry and Laboratory Medicine. 37 (4): 439–47. doi:10.1515/CCLM.1999.072. PMID 10369116. S2CID 41315909.
^ Riepe FG, Mahler P, Sippell WG, Partsch CJ (September 2002). "Longitudinal study of plasma pregnenolone and 17-hydroxypregnenolone in full-term and preterm neonates at birth and during the early neonatal period". The Journal of Clinical Endocrinology and Metabolism. 87 (9): 4301–6. doi:10.1210/jc.2002-020452. PMID 12213889.
^ Tsutsui K, Haraguchi S, Vaudry H (September 2018). "7α-Hydroxypregnenolone regulating locomotor behavior identified in the brain and pineal gland across vertebrates". General and Comparative Endocrinology. 265: 97–105. doi:10.1016/j.ygcen.2017.09.014. PMID 28919448. S2CID 5636071.

[1] Hill M, Lukác D, Lapcík O, Sulcová J, Hampl R, Pouzar V, Stárka L (April 1999). "Age relationships and sex differences in serum levels of pregnenolone and 17-hydroxypregnenolone in healthy subjects". Clinical Chemistry and Laboratory Medicine. 37 (4): 439–47. doi:10.1515/CCLM.1999.072. PMID 10369116. S2CID 41315909.

[2] Riepe FG, Mahler P, Sippell WG, Partsch CJ (September 2002). "Longitudinal study of plasma pregnenolone and 17-hydroxypregnenolone in full-term and preterm neonates at birth and during the early neonatal period". The Journal of Clinical Endocrinology and Metabolism. 87 (9): 4301–6. doi:10.1210/jc.2002-020452. PMID 12213889.

[3] Tsutsui K, Haraguchi S, Vaudry H (September 2018). "7α-Hydroxypregnenolone regulating locomotor behavior identified in the brain and pineal gland across vertebrates". General and Comparative Endocrinology. 265: 97–105. doi:10.1016/j.ygcen.2017.09.014. PMID 28919448. S2CID 5636071.

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
+{{Short description|Chemical compound}}
 {{Drugbox
 | Verifiedfields = changed
 | verifiedrevid = 477209164
-| IUPAC_name = 3β,17-dihydroxypregn-5-en-20-one
+| IUPAC_name = 3β,17α-dihydroxypregn-5-en-20-one
 | image = 17-Hydroxypregnenolone.svg
+| width = 250
 | image2 = 17-Hidroxipregnenolona3D.png
+| width2 = 250
 <!--Clinical data-->
 | tradename =
@@ Line 16: / Line 18: @@
 | legal_status =
 | routes_of_administration =
 <!--Pharmacokinetic data-->
 | bioavailability =
@@ Line 23: / Line 24: @@
 | elimination_half-life =
 | excretion =
 <!--Identifiers-->
-| CASNo_Ref = {{cascite|correct|CAS}}
 | CAS_number_Ref = {{cascite|correct|??}}
 | CAS_number = 387-79-1
+| UNII_Ref = {{fdacite|correct|FDA}}
+| UNII = 77ME40334S
 | ATC_prefix =
 | ATC_suffix =
@@ Line 37: / Line 38: @@
 | ChEBI_Ref = {{ebicite|changed|EBI}}
 | ChEBI = 28750
 <!--Chemical data-->
-| C=21 | H=32 | O=3
+| C=21 | H=32
+| O=3
-| molecular_weight = 332.48 g/mol
 | smiles = CC[C@@]2(O)CC[C@H]1[C@@H]3CCC4CC(O)C(=O)C[C@]4(C)[C@H]3CC[C@@]12C
-| InChI = 1/C21H34O3/c1-4-21(24)10-8-16-14-6-5-13-11-17(22)18(23)12-19(13,2)15(14)7-9-20(16,21)3/h13-17,22,24H,4-12H2,1-3H3/t13?,14-,15+,16+,17?,19+,20+,21-/m1/s1
-| InChIKey = QPLFSAZMHUAMKE-FOCOMJRBBT
 | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
 | StdInChI = 1S/C21H34O3/c1-4-21(24)10-8-16-14-6-5-13-11-17(22)18(23)12-19(13,2)15(14)7-9-20(16,21)3/h13-17,22,24H,4-12H2,1-3H3/t13?,14-,15+,16+,17?,19+,20+,21-/m1/s1
@@ Line 50: / Line 48: @@
 | melting_point = 268
 }}
-'''17-Hydroxypregnenolone''' (also '''17-OH-pregnenolone''' and  '''17α-hydroxypregnenolone'''), is a C21 [[steroid]] that is obtained by [[hydroxylation]] of [[pregnenolone]] at the C17α position.  This step is performed by the [[mitochondria]]l [[cytochrome P450 oxidase|cytochrome P450 enzyme]] 17α-hydroxylase ([[CYP17A1]])  that is present in the [[adrenal]] and [[gonad]]s. Peak levels are reached in humans at the end of [[puberty]] and then decline.<ref>{{cite journal | last1 = Hill | first1 = M | last2 = Lukác | first2 = D | last3 = Lapcík | first3 = O | last4 = Sulcová | first4 = J | last5 = Hampl | first5 = R | last6 = Pouzar | first6 = V | last7 = Stárka | first7 = L | title = Age relationships and sex differences in serum levels of pregnenolone and 17-hydroxypregnenolone in healthy subjects | journal = [[Clinical chemistry and laboratory medicine]] : CCLM / FESCC | volume = 37 | issue = 4 | pages = 439–47 | year = 1999 | pmid = 10369116 | doi = 10.1515/CCLM.1999.072 }}</ref> High levels are also achieved during [[pregnancy]].
+'''17α-Hydroxypregnenolone''' is a [[pregnane]] (C21) [[steroid]] that is obtained by [[hydroxylation]] of [[pregnenolone]] at the C17α position.  This step is performed by the [[mitochondria]]l [[cytochrome P450 oxidase|cytochrome P450 enzyme]] 17α-hydroxylase ([[CYP17A1]])  that is present in the [[adrenal]] and [[gonad]]s. Peak levels are reached in humans at the end of [[puberty]] and then decline.<ref>{{cite journal | vauthors = Hill M, Lukác D, Lapcík O, Sulcová J, Hampl R, Pouzar V, Stárka L | title = Age relationships and sex differences in serum levels of pregnenolone and 17-hydroxypregnenolone in healthy subjects | journal = Clinical Chemistry and Laboratory Medicine | volume = 37 | issue = 4 | pages = 439–47 | date = April 1999 | pmid = 10369116 | doi = 10.1515/CCLM.1999.072 | s2cid = 41315909 }}</ref> High levels are also achieved during [[pregnancy]]. It is also a known [[Neuromodulation|neuromodulator]].
 ==Prohormone==
+α-Hydroxypregnenolone  is considered a [[prohormone]] in the formation of [[dehydroepiandrosterone]] (DHEA), itself a prohormone of the [[sex steroid]]s.
-[[Image:DHEA1.svg|thumb|right|350px|17 OH–pregnenolone is converted from pregnenolone and gives rise to DHEA (below) and to 17 OH-progesterone (to its right)]]
--OH-pregnenolone  is considered a [[prohormone]] in the formation of [[dehydroepiandrosterone]] (DHEA), itself a prohormone of the [[sex steroid]]s.
-This conversion is mediated by the enzyme 17,20 lyase. As such 17-OH-pregenolone represents an intermediary in the delta-5-pathway that leads from pregnenolone to DHEA. 17-hydroxypregneolone is also converted to [[17-hydroxyprogesterone]], a prohormone for [[glucocorticosteroid]]s and [[androstenedione]] through the activity of 3-hydroxysteroid dehydrogenase.
+This conversion is mediated by the enzyme 17,20 lyase. As such 17α-hydroxypregenolone represents an intermediary in the Δ<sup>5</sup> pathway that leads from pregnenolone to DHEA. 17α-Hydroxypregneolone is also converted to [[17α-hydroxyprogesterone]], a prohormone for [[glucocorticosteroid]]s and [[androstenedione]] through the activity of [[3α-hydroxysteroid dehydrogenase]].
-==Neurohormone==
-There is some evidence that 17-OH-pregnenolone may have activity as a [[neurosteroid]].<ref>{{cite journal | last1 = Matsunaga | first1 = M | last2 = Ukena | first2 = K | last3 = Baulieu | first3 = EE | last4 = Tsutsui | first4 = K | title = 7α-Hydroxypregnenolone acts as a neuronal activator to stimulate locomotor activity of breeding newts by means of the dopaminergic system | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 49 | pages = 17282–7 | year = 2004 | pmid = 15569930 | pmc = 535386 | doi = 10.1073/pnas.0407176101 }}</ref>
 ==Clinical use==
-Measurements of 17-OH-pregnenolone are useful in the diagnosis of certain forms of [[congenital adrenal hyperplasia]].<ref>Riepe FG, Mahler P, Sippell, Partsch CJ. Longitudinal Study of Plasma Pregnenolone and 17-Hydroxypregnenolone in Full-Term and Preterm Neonates at Birth and during the Early Neonatal Period. The Journal of Clinical Endocrinology & Metabolism  (2002) 87: 4301-4306
+Measurements of 17α-hydroxypregnenolone are useful in the diagnosis of certain forms of [[congenital adrenal hyperplasia]].<ref>{{cite journal | vauthors = Riepe FG, Mahler P, Sippell WG, Partsch CJ | title = Longitudinal study of plasma pregnenolone and 17-hydroxypregnenolone in full-term and preterm neonates at birth and during the early neonatal period | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 87 | issue = 9 | pages = 4301–6 | date = September 2002 | pmid = 12213889 | doi = 10.1210/jc.2002-020452 | doi-access = free }}</ref>
+In patients with [[congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency]] 17α-hydroxypregnenolone is increased, while in patients with [[congenital adrenal hyperplasia due to 17α-hydroxylase deficiency]] levels are low to absent.
- [http://jcem.endojournals.org/cgi/content/full/87/9/4301]</ref>
-In patients with [[congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency]] 17-OH-pregnenolone is increased, while in patients with [[congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency]] levels are low to absent.
+== Neurosteroid ==
+α-hydroxypregnenolone is a known neuromodulator as its acts in the [[central nervous system]]. Specifically, it is known to modulate [[Animal locomotion|locomotion]].<ref>{{cite journal | vauthors = Tsutsui K, Haraguchi S, Vaudry H | title = 7α-Hydroxypregnenolone regulating locomotor behavior identified in the brain and pineal gland across vertebrates | journal = General and Comparative Endocrinology | volume = 265 | pages = 97–105 | date = September 2018 | pmid = 28919448 | doi = 10.1016/j.ygcen.2017.09.014 | s2cid = 5636071 }}</ref>
-==See also==
+== See also ==
-[[Congenital adrenal hyperplasia]]
+* [[Congenital adrenal hyperplasia]]
+* [[Narave pig]], intersex pigs that have low levels of 17α-Hydroxypregnenolone
 ==Additional images==
@@ Line 74: / Line 72: @@
 </gallery>
-==References==
+== References ==
 {{Reflist}}
+{{Endogenous steroids}}
+{{Xenobiotic-sensing receptor modulators}}
+{{DEFAULTSORT:Hydroxypregnenolone, 17α-}}
-{{Androgenics}}
-{{Estrogenics}}
-{{Progestogenics}}
-{{Steroid metabolism intermediates}}
+[[Category:Pregnane X receptor agonists]]
-{{DEFAULTSORT:Hydroxypregnenolone, 17-}}
-[[Category:Steroids]]
+[[Category:Pregnanes]]

v t e Xenobiotic-sensing receptor modulators
CARTooltip Constitutive androstane receptor	Agonists: 6,7-Dimethylesculetin Amiodarone Artemisinin Benfuracarb Carbamazepine Carvedilol Chlorpromazine Chrysin CITCO Clotrimazole Cyclophosphamide Cypermethrin DHEA (prasterone) Efavirenz Ellagic acid Griseofulvin Methoxychlor Mifepristone Nefazodone Nevirapine Nicardipine Octicizer Permethrin Phenobarbital Phenytoin Pregnanedione (5β-dihydroprogesterone) Reserpine TCPOBOP Telmisartan Tolnaftate Troglitazone Valproic acid Antagonists: 3,17β-Estradiol 3α-Androstanol 3α-Androstenol 3β-Androstanol 17-Androstanol AITC Ethinylestradiol Meclizine Nigramide J Okadaic acid PK-11195 S-07662 T-0901317
PXRTooltip Pregnane X receptor	Agonists: 17α-Hydroxypregnenolone 17α-Hydroxyprogesterone Δ⁴-Androstenedione Δ⁵-Androstenediol Δ⁵-Androstenedione AA-861 Allopregnanediol Allopregnanedione (5α-dihydroprogesterone) Allopregnanolone (brexanolone) Alpha-Lipoic acid Ambrisentan AMI-193 Amlodipine besylate Antimycotics Artemisinin Aurothioglucose Bile acids Bithionol Bosentan Bumecaine Cafestol Cephaloridine Cephradine Chlorpromazine Ciglitazone Clindamycin Clofenvinfos Chloroxine Clotrimazole Colforsin Corticosterone Cyclophosphamide Cyproterone acetate Demecolcine Dexamethasone DHEA (prasterone) DHEA-S (prasterone sulfate) Dibunate sodium Diclazuril Dicloxacillin Dimercaprol Dinaline Docetaxel Docusate calcium Dodecylbenzenesulfonic acid Dronabinol Droxidopa Eburnamonine Ecopipam Enzacamene Epothilone B Erythromycin Famprofazone Febantel Felodipine Fenbendazole Fentanyl Flucloxacillin Fluorometholone Griseofulvin Guggulsterone Haloprogin Hetacillin potassium Hyperforin Hypericum perforatum (St John's wort) Indinavir sulfate Lasalocid sodium Levothyroxine Linolenic acid: α-Linolenic acid and γ-Linolenic acid LOE-908 Loratadine Lovastatin Meclizine Metacycline Methylprednisolone Metyrapone Mevastatin Mifepristone Nafcillin Nicardipine Nicotine Nifedipine Nilvadipine Nisoldipine Norelgestromin Omeprazole Orlistat Oxatomide Paclitaxel Phenobarbital Piperine Plicamycin Prednisolone Pregnanediol Pregnanedione (5β-dihydroprogesterone) Pregnanolone Pregnenolone Pregnenolone 16α-carbonitrile Proadifen Progesterone Quingestrone Reserpine Reverse triiodothyronine Rifampicin Rifaximin Rimexolone Riodipine Ritonavir Simvastatin Sirolimus Spironolactone Spiroxatrine SR-12813 Suberoylanilide Sulfisoxazole Suramin Tacrolimus Tenylidone Terconazole Testosterone isocaproate Tetracycline Thiamylal sodium Thiothixene Thonzonium bromide Tianeptine Troglitazone Troleandomycin Tropanyl 3,5-dimethulbenzoate Zafirlukast Zeranol Antagonists: Ketoconazole Sesamin
See also Receptor/signaling modulators