Formula C21H30O3 | Molar mass 330.4611 g/mol | |
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17α-Hydroxyprogesterone (17α-OHP), or hydroxyprogesterone (OHP) (INN, BAN), also known as 17α-hydroxypregn-4-ene-3,20-dione, is an endogenous progestogen steroid hormone related to progesterone. It is also a chemical intermediate in the biosynthesis of many other endogenous steroids, including androgens, estrogens, glucocorticoids, and mineralocorticoids, as well as neurosteroids.
Contents
Under the brand name Gestageno, 17α-OHP has been marketed for clinical use in Argentina. However, esters of 17α-OHP, including hydroxyprogesterone caproate, as well as hydroxyprogesterone acetate and hydroxyprogesterone heptanoate to a much lesser extent, have been used far more widely in comparison, and when "hydroxyprogesterone" is referenced from the standpoint of medical use, what is usually being referred to is actually, in general, hydroxyprogesterone caproate.
17α-OHP is also the parent compound of a class of progestins referred to as the 17α-hydroxyprogesterone derivatives. Among others, this class of drugs includes chlormadinone acetate, cyproterone acetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, and megestrol acetate.
Production
17α-OHP is derived from progesterone via 17α-hydroxylase (encoded by CYP17A1), or from 17α-hydroxypregnenolone via 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase.
17α-OHP increases in the third trimester of pregnancy primarily due to fetal adrenal production.
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.
Biological activity
17α-OHP is an agonist of the progesterone receptor (PR) similarly to progesterone, albeit weakly in comparison. In addition, it is an antagonist of the mineralocorticoid receptor (MR) 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.
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 not 17α-OHP is also contributed by the placenta.
Earlier immunoassays like RIA (radioimmunoassay) or IRMA (immunoradiometric assay) were used to clinically determine 17α-OHP. Today more sophisticated methods use gas or liquid chromatography and mass spectrometry (e.g. LC-MS/MS).