17α-Hydroxyprogesterone
17α-Hydroxyprogesterone, also known as 17-OH progesterone, or hydroxyprogesterone, 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.
Biological activity
17α-OHP is an agonist of the progesterone receptor similarly to progesterone, albeit weakly in comparison. In addition, it is an antagonist of the mineralocorticoid receptor as well as a partial agonist of the glucocorticoid receptor, albeit with very low potency at the latter site, also similarly to progesterone.Biochemistry
Biosynthesis
17α-OHP is derived from progesterone via 17α-hydroxylase.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.
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.Immunoassays like RIA or IRMA 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 achieves greater specificity than immunoassays.
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.