17α-Hydroxyprogesterone targets the progesterone receptor (PR), where it acts as a weak agonist. It binds to cytoplasmic progesterone receptors in the reproductive system, subsequently activating progesterone receptor-mediated gene expression. As an endogenous metabolite, it also serves as a precursor for the biosynthesis of hydrocortisone and gonadal steroid hormones. The compound's activity at the PR is significantly weaker than that of progesterone itself.

In vitro, 17α-Hydroxyprogesterone is an agonist of the progesterone receptor (PR), albeit weakly compared to progesterone. It binds to PR in the reproductive system and activates PR-mediated gene expression. As an intermediate in steroidogenesis, it is metabolized by various enzymes to produce androgens, estrogens, glucocorticoids, and mineralocorticoids. Its in vitro activity is primarily studied in the context of steroid hormone biosynthesis and signaling.

In vivo, 17α-Hydroxyprogesterone induces ovarian growth and yolk production in female crabs. It increases blood pressure in sheep. In humans, it serves as a key intermediate in the biosynthesis of cortisol, androgens, and estrogens. Elevated levels of 17α-Hydroxyprogesterone are a hallmark of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. The compound is used clinically as a marker for adrenal function and in the diagnosis of adrenal disorders.

General protocols for progesterone receptor binding assays use cytosolic preparations from rabbit uterus or recombinant PR expressed in mammalian cells. Cytosol is incubated with [3H]progesterone (or [3H]R5020) and varying concentrations of 17α-Hydroxyprogesterone in binding buffer (10 mM Tris-HCl pH 7.4, 10 mM Na2MoO4, 1 mM EDTA, 2 mM DTT) at 4°C for 16-20 hours. Bound ligand is separated using dextran-coated charcoal or hydroxylapatite. Radioactivity is counted by scintillation. IC50 values are calculated from competition curves. Nonspecific binding is determined using 100-fold excess unlabeled progesterone.

General protocols for steroidogenic enzyme activity assays use microsomal or mitochondrial preparations from adrenal or gonadal tissues. 17α-Hydroxyprogesterone is incubated with appropriate cofactors (NADPH, O2) and enzyme preparations (e.g., 21-hydroxylase, 17,20-lyase) at 37°C for 30-60 minutes. Reaction products are extracted with organic solvents and analyzed by HPLC, GC-MS, or LC-MS. Enzyme activity is calculated as the rate of product formation (e.g., 11-deoxycortisol from 17-OHP via 21-hydroxylase). Michaelis-Menten kinetics are determined from substrate concentration curves.

General protocols for in vivo studies of 17α-Hydroxyprogesterone metabolism use adrenalectomized rats or mice. The compound is administered intraperitoneally or subcutaneously at doses of 1-10 mg/kg. Blood samples are collected at various time points for measurement of 17α-Hydroxyprogesterone and its metabolites by RIA, ELISA, or LC-MS. Tissues (liver, adrenal, gonads) are collected for analysis of steroidogenic enzyme activities and gene expression by qPCR or Western blot. The pharmacokinetic parameters (Cmax, Tmax, AUC, t1/2) are calculated from plasma concentration-time data.

Absorption, Distribution and Excretion
...The duration of action is longer than progesterone, but the onset of action is slower. A single injection of hydroxyprogesterone caproate oil solution can produce a progestin effect lasting 1-2 weeks. /Caproate/ Approximately 50-60% of radioactive progesterone is excreted in the urine, and approximately 10% in the feces. ...When progesterone is administered for extended periods, such as during the luteal phase of the menstrual cycle or during pregnancy, a larger proportion (25-30%) of progesterone is excreted in the urine as pregnanediol.
/Progesterone/ Endogenous progesterone has an exceptionally rapid turnover rate, with a half-life in the blood of only a few minutes; exogenous substances are undoubtedly processed in the same way. A small amount of progesterone is stored in body fat... It is presumed that it is rapidly absorbed from the intestines, but its compounds are rapidly converted as they pass through the liver... /Progesterone/

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Metabolism/Metabolites Known metabolites of 17α-hydroxyprogesterone include 17β-21-dihydroxyprogesterone. 17α-hydroxyprogesterone is a known progesterone metabolite.
17α-Hydroxyprogesterone has a short half-life in circulation due to rapid metabolism. It is produced in the adrenal glands and gonads and is secreted into the bloodstream. The compound is metabolized primarily by 21-hydroxylase (CYP21A2) to 11-deoxycortisol (a precursor of cortisol) and by 17,20-lyase (CYP17A1) to dehydroepiandrosterone (DHEA) and androstenedione (precursors of androgens and estrogens). Elimination occurs via renal excretion of metabolites. Plasma levels vary diurnally and are regulated by ACTH.

Interactions
...Estrogen enhances the inhibitory effect of progesterone, leading to the common practice of using both in combination. /Progesterone/
17α-Hydroxyprogesterone is an endogenous compound and is generally well-tolerated at physiological levels. Elevated levels, as seen in congenital adrenal hyperplasia, are associated with adrenal insufficiency and androgen excess. Therapeutic use of 17α-Hydroxyprogesterone derivatives (e.g., 17α-hydroxyprogesterone caproate) has been associated with injection site reactions, nausea, and headache. Long-term use may increase the risk of thromboembolic events. The compound should be used with caution in patients with liver disease or a history of thrombosis.

17α-Hydroxyprogesterone is a 17α-hydroxy steroid, a 17α-hydroxy derivative of progesterone. It is a metabolite, a progestin, and a metabolite found in both humans and mice. It is a 17α-hydroxy steroid, a 17α-hydroxy-C21-steroid, and a tertiary α-hydroxy ketone. Its function is related to progesterone. Hydroxyprogesterone is a progestin. Data on hydroxyprogesterone have been reported in humans and Vitex agnus-castus. Hydroxyprogesterone is a physiological progestin produced during the synthesis of glucocorticoids and steroid hormones, and its levels rise in late pregnancy (third trimester). Hydroxyprogesterone binds to cytoplasmic progesterone receptors in the reproductive system, subsequently activating progesterone receptor-mediated gene expression. It is an intermediate in the biosynthesis of hydrocortisone and gonadal steroid hormones. It is derived from progesterone via 17-hydroxylase (a P450c17 enzyme) or from 17-hydroxypregnenolone via 3-hydroxysteroid dehydrogenase/5-4 isomerase. 17-Hydroxyprogesterone is a natural progestin that rises primarily in late pregnancy due to production by the fetal adrenal glands. This hormone is mainly produced by the adrenal glands, with smaller amounts also produced by the gonads, particularly the corpus luteum of the ovary. Normal levels in children are 3-90 ng/dl, while in women it is 15-70 ng/dl before ovulation and 35-290 ng/dl during the luteal phase. Measuring 17-hydroxyprogesterone levels is helpful in assessing suspected congenital adrenal hyperplasia because the typically deficient enzymes, 21-hydroxylase and 11-hydroxylase, lead to the accumulation of 17-hydroxyprogesterone (17OHP). Conversely, in rare cases of 17-hydroxylase deficiency, 17OHP levels are very low or undetectable. 17-Hydroxyprogesterone (17OHP) levels can also be used to measure the contribution of luteal progesterone activity during pregnancy, as the placenta also produces progesterone but not 17OHP. 17OHP is a metabolite of progesterone with a hydroxyl group at the 17-α position. It is an intermediate in the biosynthesis of hydrocortisone and gonadotropic hormones. See also: hydroxyprogesterone caproate (active moiety); 17β-hydroxyprogesterone (note moved here). Mechanism of Action: Combined or sequential administration of estrogen and progesterone can interfere with fertility in a variety of ways. However, the mixtures currently in use clearly suppress ovulation. …The sustained action of progesterone suppresses the release of luteinizing hormone (LH). /Progesterone/ It acts as an antigonadotropic drug on the anterior pituitary gland, suppressing the release of follicle-stimulating hormone (FSH), thereby inhibiting follicle growth, estrogen production, and estrus. It also inhibits the release of LH, thereby preventing ovulation, corpus luteum formation, and further progesterone secretion. By inhibiting LH…progesterone levels are controlled.

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Therapeutic Uses
Therapeutic Uses: …Contraception…Dysmenorrhea…Premenstrual syndrome…Endometriosis…Threatened abortion and recurrent miscarriage…Ovarian function assessment and pregnancy diagnosis…Suppression of postpartum lactation…Endometrial cancer. /Progestin/
Chemotherapy drugs for neoplastic diseases: Hydroxyprogesterone caproate (Diletin) is used to treat endometrial cancer, renal cell carcinoma, breast cancer, and prostate cancer. /Caproate/
…Used to treat metastatic and recurrent endometrial cancer. When metastases are confined to the lungs, approximately 25% of patients achieve long-term remission. Higher doses are required when the disease recurs in the bone, abdominal, or pelvic areas. …Also used for parenteral administration in renal cancer. /Progestin/
Used to regulate irregular estrous cycles, it is usually used in combination with estrogen. /Hexanoate/
For more complete data on the therapeutic uses of 17α-hydroxyprogesterone (15 types), please visit the HSDB record page.

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Drug Warnings
Veterinarians: Avoid allowing treated animals to breed before the second post-treatment estrous cycle. Severe pyometra-like syndrome has occurred in treated animals with endometrial atrophy…
Whether the use of progestin-estrogen oral contraceptives leads to a higher incidence of ocular and oculomotor diseases than in untreated women or pregnant women is inconclusive… /Progestin/
Contraindications include thromboembolic disease or a history of it, significantly impaired liver function, known or suspected breast cancer or other estrogen-dependent tumors, and unexplained genital bleeding. /Oral Contraceptives/
17α-Hydroxyprogesterone (17-OHP) is an endogenous progestogen and a key intermediate in steroid hormone biosynthesis. It is a weak agonist of the progesterone receptor. The compound is used clinically as a diagnostic marker for congenital adrenal hyperplasia, where elevated levels indicate 21-hydroxylase deficiency. 17α-Hydroxyprogesterone caproate (a synthetic derivative) has been used for the prevention of preterm labor. The compound is also used in research on steroidogenesis and reproductive endocrinology. Regulatory approvals vary by formulation and indication.

C21H30O3

330.46

330.219

68-96-2

6238

White to off-white solid powder

1.2±0.1 g/cm3

482.9±45.0 °C at 760 mmHg

276°C

260.0±25.2 °C

0.0±2.8 mmHg at 25°C

1.560

2.89

1

3

1

24

635

6

O([H])[C@]1(C(C([H])([H])[H])=O)C([H])([H])C([H])([H])[C@@]2([H])[C@]3([H])C([H])([H])C([H])([H])C4=C([H])C(C([H])([H])C([H])([H])[C@]4(C([H])([H])[H])[C@@]3([H])C([H])([H])C([H])([H])[C@@]21C([H])([H])[H])=O

DBPWSSGDRRHUNT-CEGNMAFCSA-N

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

(8R,9S,10R,13S,14S,17R)-17-Acetyl-17-hydroxy-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one

Hydroxyprogesterone 17A-Hydroxyprogesterone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~151.30 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)