17α-Hydroxyprogesterone

Source: Wikipedia, the free encyclopedia.
"Hydroxyprogesterone" redirects here. For other uses, see Hydroxyprogesterone (disambiguation).
Not to be confused with Hydroxyprogesterone caproate or Hydroxyprogesterone acetate.
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
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
 100.000.636 Edit this at Wikidata
IUPHAR/BPS
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
C21H30O3
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).

17α-Hydroxyprogesterone (17α-OHP), also known as 17-OH progesterone (17-OHP),

chemical intermediate in the biosynthesis of many other endogenous steroids, including androgens, estrogens, glucocorticoids, and mineralocorticoids, as well as neurosteroids
.

Biological activity

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]

Relative affinities (%) of hydroxyprogesterone and related steroids
Compound hPR-A hPR-B rbPR rbGR rbER
Progesterone 100 100 100 <1 <1
17α-Hydroxyprogesterone 1 1 3 1 <1
Hydroxyprogesterone caproate 26 30 28 4 <1
Hydroxyprogesterone acetate 38 46 115 3 ?
Notes: Values are percentages (%). Reference ligands (100%) were progesterone for the PRTooltip progesterone receptor, dexamethasone for the GRTooltip glucocorticoid receptor, and estradiol for the ERTooltip estrogen receptor. Sources: See template.

Biochemistry

Steroidogenesis, showing 17α-OHP around the left-middle among the pregnenes
.

Biosynthesis

17α-OHP is derived from

17α-hydroxylase (encoded by CYP17A1)[citation needed
]

17α-OHP increases in the third trimester of pregnancy primarily due to fetal adrenal production.[citation needed]

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.[9][10]

Measurement

Measurements of levels of 17α-OHP are useful in the evaluation of patients with suspected

17α-hydroxylase deficiency will have very low or undetectable levels of 17α-OHP. 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.[citation needed
]

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.

liquid chromatography and mass spectrometry (e.g. LC-MS/MS) achieves greater specificity than immunoassays.[11][12]

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.[11][12]

Pharmacology

Pharmacokinetics

Although 17α-OHP has not been used as a medication, its pharmacokinetics have been studied and reviewed.[13]

Medical uses

See also: Hydroxyprogesterone caproate, Hydroxyprogesterone acetate, and Hydroxyprogesterone heptanoate

progestins.[2][3][4] When "hydroxyprogesterone" is referenced from the standpoint of medical use, what is usually being referred to is actually, in general, hydroxyprogesterone caproate.[citation needed
]

Chemistry

See also: List of progestogens

17α-OHP, also known as 17α-hydroxypregn-4-ene-3,20-dione, is a

hydroxyl group at the C17α position, and a double bond between the C4 and C5 positions.[citation needed
]

17α-OHP is the parent compound of a class of progestins referred to as the 17α-hydroxyprogesterone derivatives.[14][15][16] Among others, this class of drugs includes chlormadinone acetate, cyproterone acetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, and megestrol acetate.[14][15][16]

Society and culture

Generic names

Hydroxyprogesterone is the

INNTooltip International Nonproprietary Name and BANTooltip British Approved Name.[2][3][4]

See also

References

  1. ^ "17-hydroxyprogesterone (17OHP)".
  2. ^
    ISBN 978-1-4757-2085-3
    .
  3. ^
    ISBN 978-94-011-4439-1
    .
  4. ^
    ISBN 978-3-88763-075-1
    .
  5. ^
    PMID 18060946
    .
  6. S2CID 24727940
    .
  7. PMID 26207344
    .
  8. PMID 23209664
    .
  9. ^ Reference Values During Pregnancy
  10. ^ "normal ranges for hormone tests in women". Archived from the original on 2020-11-08. Retrieved 2011-08-07.
  11. ^
    PMID 33073005
    .
  12. ^
    PMID 33072992
    .
  13. ISBN 978-3-642-99941-3
    .
  14. ^
    ISBN 978-0-08-093292-7
    .
  15. ^
    ISBN 978-0-306-46278-8
    .
  16. ^
    ISBN 978-1-4831-8350-3
    .