From Wikipedia, the free encyclopedia
17α-Hydroxyprogesterone
Names
IUPAC name
17α-Hydroxypregn-4-ene-3,20-dione
Systematic IUPAC name
(1R ,3aS ,3bR ,9aR ,9bS ,11aS )-1-Acetyl-1-hydroxy-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-7H -cyclopenta[a ]phenanthren-7-one
Other names
Hydroxyprogesterone (
INN Tooltip International Nonproprietary Name )
Identifiers
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
100.000.636
KEGG
UNII
InChI=1S/C21H30O3/c1-13(22)21(24)11-8-18-16-5-4-14-12-15(23)6-9-19(14,2)17(16)7-10-20(18,21)3/h12,16-18,24H,4-11H2,1-3H3/t16-,17+,18+,19+,20+,21+/m1/s1
Key: DBPWSSGDRRHUNT-CEGNMAFCSA-N
CC(=O)[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C)O
Properties
C21 H30 O3
Molar mass
330.46 g/mol
Melting point
219.5
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
17α-Hydroxyprogesterone (17α-OHP ), also known as 17-OH progesterone (17-OHP ),
[1] or hydroxyprogesterone (OHP ), is an
endogenous
progestogen
steroid hormone related to
progesterone .
[2]
[3]
[4] It is also a
chemical intermediate in the
biosynthesis of many other endogenous steroids, including
androgens ,
estrogens ,
glucocorticoids , and
mineralocorticoids , as well as
neurosteroids .
17α-OHP is an
agonist of the
progesterone receptor (PR) similarly to progesterone, albeit weakly in comparison.
[5] In addition, it is an
antagonist of the
mineralocorticoid receptor (MR)
[6] as well as a
partial agonist of the
glucocorticoid receptor (GR), albeit with very low potency (
EC50 >100-fold less relative to
cortisol ) at the latter site, also similarly to progesterone.
[5]
[7]
[8]
Steroidogenesis , showing 17α-OHP around the left-middle among the
pregnenes .
17α-OHP is derived from
progesterone via
17α-hydroxylase (encoded by
CYP17A1 ).
[9]
17α-OHP increases in the third trimester of
pregnancy primarily due to fetal adrenal production.
[10]
This steroid is primarily produced in the
adrenal glands and to some degree in the
gonads , specifically the
corpus luteum of the
ovary . Normal levels are 3-90 ng/dl in children, and in women, 20-100 ng/dl prior to
ovulation , and 100-500 ng/dl during the
luteal phase .
[11]
[12]
Measurements of levels of 17α-OHP are useful in the evaluation of patients with suspected
congenital adrenal hyperplasia as the typical enzymes that are defective, namely
21-hydroxylase and
11β-hydroxylase , lead to a build-up of 17α-OHP.
[13] In contrast, the rare patient with
17α-hydroxylase deficiency will have very low or undetectable levels of 17α-OHP.
[9] 17α-OHP levels can also be used to measure contribution of progestational activity of the corpus luteum during pregnancy as progesterone but note, 17α-OHP is also contributed by the
placenta .
[14]
Immunoassays like RIA (
radioimmunoassay ) or IRMA (immunoradiometric
assay) used to clinically determine 17α-OHP are prone to cross-reactivity with the 17α-OHP steroid precursors and their sulphated conjugates.
Gas or
liquid chromatography and
mass spectrometry (e.g. LC-MS/MS) achieves greater specificity than immunoassays.
[15]
[16]
Measurement of 17α-OHP by LC-MS/MS improves newborn screening for
congenital adrenal hyperplasia due to 21-hydroxylase deficiency , because 17α-OHP steroid precursors and their sulphated conjugates which are present in the first two days after birth and longer in pre-term neonates, cross-react in immunoassays with 17α-OHP, giving falsely high 17α-OHP levels.
[15]
[16]
Although 17α-OHP has not been used as a medication, its
pharmacokinetics have been studied and reviewed.
[17]
Esters of 17α-OHP, such as
hydroxyprogesterone caproate and, to a far lesser extent,
hydroxyprogesterone acetate and
hydroxyprogesterone heptanoate , have been used in medicine as
progestins .
[2]
[3]
[4]
17α-OHP is the parent compound of a class of progestins referred to as the 17α-hydroxyprogesterone derivatives .
[18]
[19]
[20] Among others, this class of drugs includes
chlormadinone acetate ,
cyproterone acetate ,
hydroxyprogesterone caproate ,
medroxyprogesterone acetate , and
megestrol acetate .
[18]
[19]
[20]
Hydroxyprogesterone is the
generic name of 17α-OHP and its
INN Tooltip International Nonproprietary Name and
BAN Tooltip British Approved Name .
[2]
[3]
[4]
^
"17-hydroxyprogesterone (17OHP)" .
^
a
b
c J. Elks (14 November 2014).
The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies . Springer. pp. 664–665.
ISBN
978-1-4757-2085-3 .
^
a
b
c I.K. Morton, Judith M. Hall (6 December 2012).
Concise Dictionary of Pharmacological Agents: Properties and Synonyms . Springer Science & Business Media. pp. 146–.
ISBN
978-94-011-4439-1 .
^
a
b
c
Index Nominum 2000: International Drug Directory . Taylor & Francis. January 2000. pp. 532–.
ISBN
978-3-88763-075-1 .
^
a
b Attardi BJ, Zeleznik A, Simhan H, Chiao JP, Mattison DR, Caritis SN (2007).
"Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins" . Am. J. Obstet. Gynecol . 197 (6): 599.e1–7.
doi :
10.1016/j.ajog.2007.05.024 .
PMC
2278032 .
PMID
18060946 .
^ Mooij CF, Parajes S, Pijnenburg-Kleizen KJ, Arlt W, Krone N, Claahsen-van der Grinten HL (April 2015).
"Influence of 17-Hydroxyprogesterone, Progesterone and Sex Steroids on Mineralocorticoid Receptor Transactivation in Congenital Adrenal Hyperplasia" (PDF) . Horm Res Paediatr . 83 (6): 414–421.
doi :
10.1159/000374112 .
PMID
25896481 .
S2CID
24727940 .
^ Pijnenburg-Kleizen KJ, Engels M, Mooij CF, Griffin A, Krone N, Span PN, van Herwaarden AE, Sweep FC, Claahsen-van der Grinten HL (2015).
"Adrenal Steroid Metabolites Accumulating in Congenital Adrenal Hyperplasia lead to Transactivation of the Glucocorticoid Receptor" . Endocrinology . 156 (10): 3504–3510.
doi :
10.1210/en.2015-1087 .
PMID
26207344 .
^ Sun K, Lei K, Chen L, Georgiou EX, Sooranna SR, Khanjani S, Brosens JJ, Bennett PR, Johnson MR (2012).
"Progesterone Acts via the Nuclear Glucocorticoid Receptor to Suppress IL-1β-Induced COX-2 Expression in Human Term Myometrial Cells" . PLOS ONE . 7 (11): e50167.
Bibcode :
2012PLoSO...750167L .
doi :
10.1371/journal.pone.0050167 .
ISSN
1932-6203 .
PMC
3509141 .
PMID
23209664 .
^
a
b Kim SM, Rhee JH (2015).
"A case of 17 alpha-hydroxylase deficiency" . Clinical and Experimental Reproductive Medicine . 42 (2). The Korean Society for Reproductive Medicine: 72–76.
doi :
10.5653/cerm.2015.42.2.72 .
ISSN
2233-8233 .
PMC
4496435 .
PMID
26161337 .
^ Tal R, Taylor HS (2021-03-18).
"Endocrinology of Pregnancy" . MDText.com, Inc.
PMID
25905197 . Retrieved 2024-06-25 .
^
Reference Values During Pregnancy
^
"normal ranges for hormone tests in women" . Archived from
the original on 2020-11-08. Retrieved 2011-08-07 .
^ Held PK, Bird IM, Heather NL (2020-08-23).
"Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy" . International Journal of Neonatal Screening . 6 (3). MDPI AG: 67.
doi :
10.3390/ijns6030067 .
ISSN
2409-515X .
PMC
7569755 .
PMID
33117906 .
^ Check JH, Vaze MM, Epstein R, Wu CH, Quattrocchi J, Vetter B (1990). "17-Hydroxyprogesterone level as a marker for corpus luteum function in aborters versus nonaborters". International Journal of Fertility . 35 (2): 112–115.
ISSN
0020-725X .
PMID
1970979 .
^
a
b de Hora MR, Heather NL, Patel T, Bresnahan LG, Webster D, Hofman PL (March 2020).
"Measurement of 17-Hydroxyprogesterone by LCMSMS Improves Newborn Screening for CAH Due to 21-Hydroxylase Deficiency in New Zealand" . International Journal of Neonatal Screening . 6 (1): 6.
doi :
10.3390/ijns6010006 .
PMC
7422986 .
PMID
33073005 .
^
a
b Bialk ER, Lasarev MR, Held PK (September 2019).
"Wisconsin's Screening Algorithm for the Identification of Newborns with Congenital Adrenal Hyperplasia" . International Journal of Neonatal Screening . 5 (3): 33.
doi :
10.3390/ijns5030033 .
PMC
7510207 .
PMID
33072992 .
^
Die Gestagene . Springer-Verlag. 27 November 2013. pp. 276–277.
ISBN
978-3-642-99941-3 .
^
a
b Jeffrey K. Aronson (21 February 2009).
Meyler's Side Effects of Endocrine and Metabolic Drugs . Elsevier. pp. 289–.
ISBN
978-0-08-093292-7 .
^
a
b Robert Alan Prentky, Ann Wolbert Burgess (31 July 2000).
Forensic Management of Sexual Offenders . Springer Science & Business Media. pp. 219–.
ISBN
978-0-306-46278-8 .
^
a
b H. J. Smith, Hywel Williams (1 January 1983).
Introduction to the Principles of Drug Design . Elsevier. pp. 187–.
ISBN
978-1-4831-8350-3 .
GR Tooltip Glucocorticoid receptor
MR Tooltip Mineralocorticoid receptor
PR Tooltip Progesterone receptor
Agonists
Testosterone derivatives: Progestins:
6,6-Difluoronorethisterone
6,6-Difluoronorethisterone acetate
17α-Allyl-19-nortestosterone
Allylestrenol
Altrenogest
Chloroethynylnorgestrel
Cingestol
Danazol
Desogestrel
Dienogest
Ethinylandrostenediol
Ethisterone
Ethynerone
Etonogestrel
Etynodiol
Etynodiol diacetate
Gestodene
Gestrinone
Levonorgestrel
Levonorgestrel esters (e.g.,
levonorgestrel butanoate )
Lynestrenol
Lynestrenol phenylpropionate
Metynodiol
Metynodiol diacetate
Norelgestromin
Norethisterone (norethindrone)
Norethisterone esters (e.g.,
norethisterone acetate ,
norethisterone enanthate )
Noretynodrel
Norgesterone
Norgestimate
Norgestrel
Norgestrienone
Norvinisterone
Oxendolone
Quingestanol
Quingestanol acetate
Tibolone
Tigestol
Tosagestin ; Anabolic–androgenic steroids:
11β-Methyl-19-nortestosterone
11β-Methyl-19-nortestosterone dodecylcarbonate
19-Nor-5-androstenediol
19-Nor-5-androstenedione
19-Nordehydroepiandrosterone
Bolandiol
Bolandiol dipropionate
Bolandione
Dimethisterone
Dienedione
Dienolone
Dimethandrolone
Dimethandrolone buciclate
Dimethandrolone dodecylcarbonate
Dimethandrolone undecanoate
Dimethyldienolone
Dimethyltrienolone
Ethyldienolone
Ethylestrenol (ethylnandrol)
Methyldienolone
Metribolone (R-1881)
Methoxydienone (methoxygonadiene)
Mibolerone
Nandrolone
Nandrolone esters (e.g.,
nandrolone decanoate ,
nandrolone phenylpropionate )
Norethandrolone
Normethandrone (methylestrenolone, normethandrolone, normethisterone)
RU-2309
Tetrahydrogestrinone
Trenbolone (trienolone)
Trenbolone esters (e.g.,
trenbolone acetate ,
trenbolone enanthate )
Trendione
Trestolone
Trestolone acetate
Mixed (
SPRMs Tooltip Selective progesterone receptor modulators ) Antagonists
mPR Tooltip Membrane progesterone receptor (
PAQR Tooltip Progestin and adipoQ receptor )
CAR Tooltip Constitutive androstane receptor
PXR Tooltip Pregnane X receptor