17α-Hydroxyprogesterone

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]

Biosynthesis

17α-OHP is derived from progesterone via 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 congenital adrenal hyperplasia as the typical enzymes that are defective, namely 21-hydroxylase and 11β-hydroxylase, lead to a build-up of 17α-OHP. In contrast, the rare patient with 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 (immunoradiometricassay) 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.^[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]

Pharmacokinetics

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

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] When "hydroxyprogesterone" is referenced from the standpoint of medical use, what is usually being referred to is actually, in general, hydroxyprogesterone caproate.^{[citation needed]}

17α-OHP, also known as 17α-hydroxypregn-4-ene-3,20-dione, is a naturally occurring pregnane steroid. It features ketone groups at the C3 and C20 positions, 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]

Generic names

Hydroxyprogesterone is the generic name of 17α-OHP and its INNTooltip International Nonproprietary Name and BANTooltip British Approved Name.^[2][3][4]

• 11α-Hydroxyprogesterone
• 5α-Dihydroprogesterone
• 20-Dihydroprogesterone
• 11-Deoxycorticosterone
• 11-Deoxycortisol
• 17α-Methylprogesterone
• 19-Norprogesterone
• 19-Nortestosterone