17α-Hydroxyprogesterone (17α-OHP), also known as 17-OH progesterone (17-OHP), or hydroxyprogesterone (OHP), is an

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...

progestogen Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. ...

steroid hormone related to

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...

. It is also a chemical intermediate in the

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

of many other endogenous steroids, including androgens, estrogens, glucocorticoids, and mineralocorticoids, as well as

neurosteroid Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term ''neurosteroid'' was coin ...

Biological activity

17α-OHP is an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the

progesterone receptor The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone. In humans, PR is encoded by a single ''PGR'' gene resid ...

(PR) similarly to progesterone, albeit weakly in comparison. In addition, it is an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

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 Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...

) at the latter site, also similarly to progesterone.

Biochemistry

Biosynthesis

17α-OHP is derived from

via

17α-hydroxylase Cytochrome P450 17A1 (steroid 17α-monooxygenase, 17α-hydroxylase, 17-alpha-hydroxylase, 17,20-lyase, 17,20-desmolase) is an enzyme of the hydroxylase type that in humans is encoded by the ''CYP17A1'' gene on chromosome 10. It is ubiquitously expr ...

(encoded by CYP17A1) 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

gonad A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...

s, specifically the

corpus luteum The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is t ...

of the

ovary The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. ...

. 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.normal ranges for hormone tests in women
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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 Steroid 21-hydroxylase (also known as steroid 21-monooxygenase, cytochrome P450C21, 21α-hydroxylase and less commonly 21β-hydroxylase) is an enzyme that hydroxylates steroids at the C21 position and is involved in biosynthesis of aldosterone a ...

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 ( 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 Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is use ...

(e.g. LC-MS/MS) 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.

Pharmacology

Pharmacokinetics

Although 17α-OHP has not been used as a medication, its

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...

have been studied and reviewed.

Medical uses

Esters of 17α-OHP, such as hydroxyprogesterone caproate and, to a far lesser extent,

hydroxyprogesterone acetate Hydroxyprogesterone acetate (OHPA), sold under the brand name Prodox, is an orally active progestin related to hydroxyprogesterone caproate (OHPC) which has been used in clinical and veterinary medicine. It has reportedly also been used in bi ...

and

hydroxyprogesterone heptanoate Hydroxyprogesterone heptanoate (OHPH), also known as hydroxyprogesterone enanthate (OHPE) and sold under the brand names H.O.P., Lutogil A.P., and Lutogyl A.P. among others, is a progestin medication used for progestogenic indications. It has b ...

, have been used in medicine as

progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...

s. When "hydroxyprogesterone" is referenced from the standpoint of medical use, what is usually being referred to is actually, in general, hydroxyprogesterone caproate.

Chemistry

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

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

. It features

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...

groups at the C3 and C20 positions, a

hydroxyl group In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy g ...

at the C17α position, and a double bond between the C4 and C5 positions. 17α-OHP is 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 Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of bi ...

, and megestrol acetate.

Society and culture

Generic names

''Hydroxyprogesterone'' is the generic name of 17α-OHP and its and .

References

{{DEFAULTSORT:Hydroxyprogesterone, 17α Antimineralocorticoids Diketones Glucocorticoids Pregnane X receptor agonists Pregnanes Progestogens