WordNet

first in order of importance; "the alpha male in the group of chimpanzees"; "the alpha star in a constellation is the brightest or main star"
the 1st letter of the Greek alphabet
the beginning of a series or sequence; "the Alpha and Omega, the first and the last, the beginning and the end"--Revelations
early testing stage of a software or hardware product; "alpha version"
any high mountain

PrepTutorEJDIC

アルファ(ギリシア語アルファベットの第1字A,α;英語のA,aに相当) / アルファ星(星座の主星)
高山,高峰

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/12 09:27:18」(JST)

wiki en

17-Hydroxyprogesterone (17-OHP) is an endogenous progestogen as well as chemical intermediate in the biosynthesis of other steroid hormones, including the corticosteroids and the androgens and the estrogens.

Production

It is derived from progesterone via 17-hydroxylase, a P450c17 enzyme, or from 17-hydroxypregnenolone via 3β-hydroxysteroid dehydrogenase/Δ^5-4 isomerase.

17-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.^[2]^[3]

Biological activity

17-OHP is an agonist of the progesterone receptor (PR) similarly to progesterone, albeit weakly in comparison.^[4] 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.^[4]^[5]^[6]

17-Hydroxyprogesterone caproate

17-OHP is not the same compound as 17-hydroxyprogesterone caproate (17-OHPC), the latter being the caproic acid of 17-hydroxyprogesterone that was first clinically introduced as an injectable version of the steroid under the name of Delalutin in 1956.

The use of 17-OHPC in pregnancy to prevent preterm birth has a long history. A 2006 Cochrane Review concluded "...important maternal and infant outcomes have been poorly reported to date... information regarding the potential harms of progesterone therapy to prevent preterm birth is limited".^[7] There was a similar conclusion from a review by Marc Keirse.^[8] Three clinical studies of 250 mg/week of i.m. 17-OHPC showed a trend for an increase in pregnancy loss due to miscarriage compared to placebo.^[9]^[10]^[11]^[12] There had been speculation that the castor oil in some 17-OHPC formulations may not be beneficial for pregnancy.^[13]^[14]

In contrast, a large NIH study in 2003 looked at the effect of 17-OHPC injections in women at risk for repeat premature birth and found that the treated group experienced premature birth in 37% versus 55% in the controls.^[15]

A follow-up study of the offspring showed no evidence that 17-OHPC affected the children in the first years of life.^[16] Based on these NIH data, 17 OHPC was approved by the FDA in 2011 as a drug to reduce the risk of premature birth in selected patients at risk. (v.i.)

17-OHPC is a category B drug according to the FDA.

Clinical use

Measurement

Measurements of levels of 17-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 17-OHP. In contrast, the rare patient with 17α-hydroxylase deficiency will have very low or undetectable levels of 17-OHP. 17-OHP levels can also be used to measure contribution of progestational activity of the corpus luteum during pregnancy as progesterone but not 17-OHP is also contributed by the placenta.

Medication

17-OHPC was first introduced in 1956 as Delalutin to reduce pregnancy loss. After decades of use, Squibb, the manufacturer, voluntarily withdrew the brand, however, physicians continued to use 17-OHPC "off label". Renewed interest was sparked with a large NIH-sponsored study in 2003 that found that 17-OHPC reduced the risk of premature birth in selected at-risk pregnant women.^[15] With follow-up data showing no evidence of harmful effects on the offspring, the FDA approved the drug, as sponsored by KV Pharmaceutical as Makena, as an orphan drug in February 2011 to reduce the risk of premature birth in women prior to 37 weeks gestation with a single fetus who had at least one previous premature birth.^[17] The drug is not effective in preventing premature birth in women with multiples. With the arrival of Makena as an orphan drug, the price of the drug was to increase from $15 to $1,500 per dose meaning a typical treatment would cost $25–30,000, - a pricing strategy that was strongly criticized. The FDA then announced that pharmacies could continue to compound the drug at their usual cost of $10~20 per dose without fear of legal reprisals.,^[18] and KV reduced its price to $690 per dose.^[19]

17-Hydroxyprogesterone (17-OH-Prog in the diagram) may arise from either of two steroid precursors.

Determination

Earlier immunoassays like RIA (radioimmunoassay) or IRMA (immunoradiometric assay) were used to clinically determine 17-Hydroxyprogesterone. Today more sophisticated methods use gas or liquid chromatography and mass spectrometry (e.g. LC-MS/MS).

Additional images

Steroidogenesis
17-Hydroxypregnenolone
Progesterone
Androstenedione
11-Deoxycortisol

Synthesis

Hydroxyprogesterone synthesis:^[20] U.S. Patent 2,802,839

References

^ Pharmacokinetics of 17-hydroxyprogesterone caproate in multifetal gestation.
^ Reference Values During Pregnancy
^ normal ranges for hormone tests in women
^ ^a ^b Attardi BJ, Zeleznik A, Simhan H, Chiao JP, Mattison DR, Caritis SN (2007). "Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins". Am. J. Obstet. Gynecol. 197 (6): 599.e1–7. doi:10.1016/j.ajog.2007.05.024. PMC 2278032. PMID 18060946.
^ Pijnenburg-Kleizen KJ, Engels M, Mooij CF, Griffin A, Krone N, Span PN, et al. (2015). "Adrenal Steroid Metabolites Accumulating in Congenital Adrenal Hyperplasia lead to Transactivation of the Glucocorticoid Receptor". Endocrinology: en20151087. doi:10.1210/en.2015-1087. PMID 26207344.
^ Sun, Kang; Lei, Kaiyu; Chen, Li; Georgiou, Ektoras X.; Sooranna, Suren R.; Khanjani, Shirin; Brosens, Jan J.; Bennett, Phillip R.; Johnson, Mark R. (2012). "Progesterone Acts via the Nuclear Glucocorticoid Receptor to Suppress IL-1β-Induced COX-2 Expression in Human Term Myometrial Cells". PLoS ONE 7 (11): e50167. doi:10.1371/journal.pone.0050167. ISSN 1932-6203.
^ Dodd JM, Flenady V, Cincotta R, Crowther CA; The Cochrane Database of Systematic Reviews 2006 Issue 1
^ Keirse MJNC. Progesterone and Preterm: Seventy Years of "Deja vu" or "Still To Be Seen"?. Birth, 2004 September; 31:3.
^ Johnson JWC, Austin KL, Jones GS, Davis GH, King TM. Efficacy of 17 alpha-hydroxyprogesterone caproate in the prevention of premature labor. NEJM 1975 October. 293(14):675.
^ Yemini M, Borenstein R, Dreazen, et al. Prevention of premature labor by 17 alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol. 1985;151(5):574-7.
^ Meis PJ et al. Prevention of Recurrent Preterm Delivery by 17 Alpha-hydroxyprogesterone Caproate. NEJM, 2003: vol 348, no 24, pg 2379-2385.
^ Keirse MJNC, Progestogen administration in pregnancy may prevent preterm delivery. Br J Obstet Gynecol 1990 February; 97:149.
^ Duke University Medical Center, New England Journal of Medicine, correspondence, vol 349.
^ Hauth JC, Gilstrap LC, Brekken AL, Hauth JM. The effect of 17 alpha-hydroxyprogesterone caproate on pregnancy outcome in an active-duty military population. Am J Obstet Gynecol. 1983 May; 146(2): 187.
^ ^a ^b Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. (2003). "Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.". N Engl J Med. 348 (24): 2379–85. doi:10.1056/NEJMoa035140. PMID 12802023.
^ Northen AT, Norman GS, Anderson K, Moseley L, Divito M, Cotroneo M, Swain M, Bousleiman S, Johnson F, Dorman K, Milluzzi C, Tillinghast JA, Kerr M, Mallett G, Thom E, Pagliaro S, Anderson GD; National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. (2007). "Follow-up of children exposed in utero to 17 alpha-hydroxyprogesterone caproate compared with placebo". Obstet Gynecol. 110 (4): 865–72. doi:10.1097/01.AOG.0000281348.51499.bc. PMID 17906021.
^ FDA press release regarding Makena approval
^ http://www.macleans.ca/article.jsp?content=w6411446
^ "Price of preterm birth medicine cut". Boston.com. Associated Press. April 2, 2011. Retrieved April 2, 2011.
^ Ringold, H. J.; Löken, B.; Rosenkranz, G.; Sondheimer, F. (1956). "Steroids. LXXIII.1a The Direct Oppenauer Oxidation of Steroidal Formate Esters. A New Synthesis of 17α-Hydroxyprogesterone1b". Journal of the American Chemical Society 78 (4): 816. doi:10.1021/ja01585a030.

External links

Chemical database at ualberta.ca
Prescribing information for Makena

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 自然早産のリスクを低下させるためのプロゲステロン補充 progesterone supplementation to reduce the risk of spontaneous preterm birth
2. 思春期における多嚢胞性卵巣症候群の診断的評価 diagnostic evaluation of polycystic ovary syndrome in adolescents
3. Uncommon congenital adrenal hyperplasias
4. Causes of primary amenorrhea
5. 副腎ステロイド生合成 adrenal steroid biosynthesis

English Journal

Relationship between interpregnancy interval and cervical length in high-risk women.

Subramaniam A1, Wetta LL, Owen J.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.J Matern Fetal Neonatal Med.2015 May 18:1-4. [Epub ahead of print]
OBJECTIVE: Our objective was to evaluate the relationship between the interpregnancy interval (IPI) and next-pregnancy mid-trimester cervical length (CL) in women at high risk for recurrent spontaneous preterm birth (SPTB).METHODS: Retrospective review identified high-risk women, defined as a prior
PMID 25983138

Relation of body mass index to frequency of recurrent preterm birth in women treated with 17-alpha hydroxyprogesterone caproate.

Co AL1, Walker HC2, Hade EM3, Iams JD4.
American journal of obstetrics and gynecology.Am J Obstet Gynecol.2015 Apr 23. pii: S0002-9378(15)00382-8. doi: 10.1016/j.ajog.2015.04.018. [Epub ahead of print]
OBJECTIVE: The standard weekly dose of 17-alpha hydroxyprogesterone caproate (17OHP-C; 250 mg/wk) to reduce the risk of recurrent preterm birth was adopted without regard to patient characteristics. We examined the relationship between prepregnancy body mass index (BMI) and gestational age at birth
PMID 25912300

17 alpha-hydroxyprogesterone caproate does not prolong pregnancy or reduce the rate of preterm birth in women at high risk for preterm delivery and a short cervix: a randomized controlled trial.

Winer N1, Bretelle F2, Senat MV3, Bohec C4, Deruelle P5, Perrotin F6, Connan L7, Vayssière C8, Langer B9, Capelle M10, Azimi S11, Porcher R12, Rozenberg P13; Groupe de Recherche en Obstétrique et Gynécologie.
American journal of obstetrics and gynecology.Am J Obstet Gynecol.2015 Apr;212(4):485.e1-485.e10. doi: 10.1016/j.ajog.2014.10.1097. Epub 2014 Oct 30.
OBJECTIVE: The objective of the study was to evaluate the efficacy of 17 alpha-hydroxyprogesterone caproate (17OHP-C) in prolonging gestation in patients with a short cervix and other risk factors for preterm delivery, such as previous preterm birth, cervical surgery, uterine anomalies, or prenatal
PMID 25448515

Japanese Journal

Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate

N Engl J Med 348, 2379-2385, 2003
NAID 30022558747

Adequate interval of sGTH administration to induce vitellogenesis, and induction of ovulation by simultaneous administration of sGTH and 17.ALPHA.-hydroxyprogesterone in the Japanese eel.

Fisheries science 66(4), 644-654, 2000
NAID 130003903465

In Vitro Effects of 17.ALPHA.-hydroxyprogesterone and 17.ALPHA.,20.BETA.-dihydroxy-4-pregnen-3-one on Final Maturation of Oocytes at Various Developmental Stages in Artificially Matured Japanese Eel Anguilla japonica.

Fisheries science 61(6), 1012-1015, 1995
NAID 130003902818

Related Pictures

★リンクテーブル★

リンク元	「17α-ヒドロキシプロゲステロン」
関連記事	「alpha」「hydroxyprogesterone」

「17α-ヒドロキシプロゲステロン」

17-Hydroxyprogesterone
Systematic (IUPAC) name
	17-Hydroxypregn-4-ene-3,20-dione
Clinical data
Licence data	US FDA:link
Pregnancy; category	US: B (No risk in non-human studies); B;
Legal status	US: ℞-only;
Pharmacokinetic data
Metabolism	Liver
Biological half-life	10 days (17-OHPC)
Identifiers
CAS Registry Number	68-96-2
ATC code	G03DA03
PubChem	CID: 6238
IUPHAR/BPS	5104
ChemSpider	6002
UNII	21807M87J2
ChEBI	CHEBI:17252
ChEMBL	CHEMBL1062
Chemical data
Formula	C21H30O3
Molecular mass	330.46 g/mol
	SMILES O=C4\C=C2/[C@]([C@H]1CC[C@@]3([C@@](O)(C(=O)C)CC[C@H]3[C@@H]1CC2)C)(C)CC4 ;
	InChI 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 ; Key:DBPWSSGDRRHUNT-CEGNMAFCSA-N ;
Physical data
Melting point	219.5 °C (427.1 °F)
(what is this?) (verify)

　　[★]

英: 17-alpha-hydroxyprogesterone 17α-hydroxyprogesterone 17α-OHP, 17-OHP
同: 17αヒドロキシプロゲステロン、17-OHプロゲステロン、17α-ヒドロキシプロジェステロン
関: 副腎皮質ホルモン

概念

黄体ホルモン、プロゲステロンの水酸化物

臨床関連

先天性副腎過形成

女性仮性半陰陽
新生児マススクリーニングにおいて先天性副腎過形成症のマーカーとなる。

「alpha」

　　[★]

α、アルファ

関: alfa

「hydroxyprogesterone」

　　[★] ヒドロキシプロゲステロン

[1] Pharmacokinetics of 17-hydroxyprogesterone caproate in multifetal gestation.

[2] Reference Values During Pregnancy

[3] rmal ranges for hormone tests in women

[pmid18060946-4] Attardi BJ, Zeleznik A, Simhan H, Chiao JP, Mattison DR, Caritis SN (2007). "Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins". Am. J. Obstet. Gynecol. 197 (6): 599.e1–7. doi:10.1016/j.ajog.2007.05.024. PMC 2278032. PMID 18060946.

[pmid26207344-5] Pijnenburg-Kleizen KJ, Engels M, Mooij CF, Griffin A, Krone N, Span PN, et al. (2015). "Adrenal Steroid Metabolites Accumulating in Congenital Adrenal Hyperplasia lead to Transactivation of the Glucocorticoid Receptor". Endocrinology: en20151087. doi:10.1210/en.2015-1087. PMID 26207344.

[SunLei2012-6] Sun, Kang; Lei, Kaiyu; Chen, Li; Georgiou, Ektoras X.; Sooranna, Suren R.; Khanjani, Shirin; Brosens, Jan J.; Bennett, Phillip R.; Johnson, Mark R. (2012). "Progesterone Acts via the Nuclear Glucocorticoid Receptor to Suppress IL-1β-Induced COX-2 Expression in Human Term Myometrial Cells". PLoS ONE 7 (11): e50167. doi:10.1371/journal.pone.0050167. ISSN 1932-6203.

[7] Dodd JM, Flenady V, Cincotta R, Crowther CA; The Cochrane Database of Systematic Reviews 2006 Issue 1

[8] Keirse MJNC. Progesterone and Preterm: Seventy Years of "Deja vu" or "Still To Be Seen"?. Birth, 2004 September; 31:3.

[9] Johnson JWC, Austin KL, Jones GS, Davis GH, King TM. Efficacy of 17 alpha-hydroxyprogesterone caproate in the prevention of premature labor. NEJM 1975 October. 293(14):675.

[10] Yemini M, Borenstein R, Dreazen, et al. Prevention of premature labor by 17 alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol. 1985;151(5):574-7.

[11] Meis PJ et al. Prevention of Recurrent Preterm Delivery by 17 Alpha-hydroxyprogesterone Caproate. NEJM, 2003: vol 348, no 24, pg 2379-2385.

[12] Keirse MJNC, Progestogen administration in pregnancy may prevent preterm delivery. Br J Obstet Gynecol 1990 February; 97:149.

[13] Duke University Medical Center, New England Journal of Medicine, correspondence, vol 349.

[14] Hauth JC, Gilstrap LC, Brekken AL, Hauth JM. The effect of 17 alpha-hydroxyprogesterone caproate on pregnancy outcome in an active-duty military population. Am J Obstet Gynecol. 1983 May; 146(2): 187.

[nih2003-15] Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. (2003). "Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.". N Engl J Med. 348 (24): 2379–85. doi:10.1056/NEJMoa035140. PMID 12802023.

[16] Northen AT, Norman GS, Anderson K, Moseley L, Divito M, Cotroneo M, Swain M, Bousleiman S, Johnson F, Dorman K, Milluzzi C, Tillinghast JA, Kerr M, Mallett G, Thom E, Pagliaro S, Anderson GD; National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. (2007). "Follow-up of children exposed in utero to 17 alpha-hydroxyprogesterone caproate compared with placebo". Obstet Gynecol. 110 (4): 865–72. doi:10.1097/01.AOG.0000281348.51499.bc. PMID 17906021.

[17] FDA press release regarding Makena approval

[18] ttp://www.macleans.ca/article.jsp?content=w6411446

[19] "Price of preterm birth medicine cut". Boston.com. Associated Press. April 2, 2011. Retrieved April 2, 2011.

[20] Ringold, H. J.; Löken, B.; Rosenkranz, G.; Sondheimer, F. (1956). "Steroids. LXXIII.1a The Direct Oppenauer Oxidation of Steroidal Formate Esters. A New Synthesis of 17α-Hydroxyprogesterone1b". Journal of the American Chemical Society 78 (4): 816. doi:10.1021/ja01585a030.

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案内

17-alpha-hydroxyprogesterone