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PubMed1980

Amniotic 17-alpha hydroxyprogesterone and HLA typing for the prenatal diagnosis of 21-alpha hydroxylase deficiency--congenital adrenal hyperplasia.

We have investigated a family with one child affected with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Prenatal determination of 17-alpha hydroxyprogesterone (17OHP) in amniotic fluid (AF) and HLA typing of amniotic fibroblasts from a pregnancy at risk showed that the fetus was not affected. A healthy cousin with HLA haplotypes identical to those of the proposita (only one being identical by descent) had a normal plasma level of 17OHP. The prenatal diagnosis of a fetus affected with 21-hydroxylase deficiency CAH may be established by the determination of 17OHP in AF. This is a relatively quick procedure that can be confirmed by the HLA genotype, and is mandatory in families with a parent homozygous for an HLA haplotype and in certain recombinant haplotypes in the fetus.

Adrenal Hyperplasia, Congenital↗
PubMedDate not supplied

A comparative study of the efficiency of hydroxyprogesterone caproate and of chlormadinone acetate in the prevention of premature labor.

The efficacy of caproate of hydroxyprogesterone and acetate of chlormadinone in preventing premature labore was compared in a controlled trial. The survey was based on 211 pregnant women with a high risk of premature delivery discovered during clinical examination. There are no significant differences between the two groups in either length of gestation, delay between the beginning of treatment and delivery or other parameters related to prematurity. The absence of evidence suggesting any significant difference between the two treatments can have three possible causes (which are discussed): the methodology, the inefficacy of the two products or the equivalent efficacy of the two products.

Chlormadinone Acetate↗
PubMed1990

A microcompartmentation analysis of intermediate leakage response to substrate excess in a membrane-bound bifunctional enzyme: local control of hydroxyprogesterone channeling efficiency during cytochrome P450XVII-catalysed androgen biosynthesis.

Evidence is presented for the first time that the cytochrome P450XVII-catalysed androgen formation from progesterone (P) in rat testicular microsomal membranes represents a metabolic sequence that exhibits the ability of intrinsic regulation of intermediate transfer and product formation efficiency. Exposure of this system, which catalyses a hydroxylation and oxidative cleavage reaction sequence, to increasing P concentration results in a decreased specific retention of the putative intermediate, 17 alpha-hydroxyprogesterone (HP) in the membrane compartment, and in a decreased HP conversion to androgens in favour of increasing HP transfer into the extramembrane space. This behaviour results in a decreased ratio of product vs. intermediate formation rates, which is interpreted as a partial "uncoupling" of the normal hydroxylation and cleavage reaction sequence catalysed by P450XVII. A similar pattern can likewise be observed in isolated testicular Leydig cells after exposure to increasing P concentrations under more physiological continuous-flow conditions. Further calculations indirectly indicate that the specific retention of HP in the membrane compartment can partially be attributed to its specific association with the P450XVII during catalysis. The results strongly suggest the existence of a local "channel" that becomes more leaky and therefore less effective if loaded with high influx rates. This pattern may be related to significant but incomplete competition of exogenously entering P and endogenously formed and transiently bound HP for oxygen attack at the P450XVII active site.

Androgens↗
PubMed2002

Rapid screening assay of congenital adrenal hyperplasia by measuring 17 alpha-hydroxyprogesterone with high-performance liquid chromatography/electrospray ionization tandem mass spectrometry from dried blood spots.

A rapid, simple, and specific method was developed for the diagnosis of congenital adrenal hyperplasia (CAH) from dried blood spots on newborn screening cards based on high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). The usefulness of 17 alpha-hydroxyprogesterone (17 OH-P) determination on dried filter-paper blood samples from patients with CAH caused by 21-hydroxylase deficiency was evaluated. The LC/MS/MS detection of 17 OH-P was rapid, <4 min. The intra- and interday accuracy and precision of the method were <7%. Our procedure maintained good linearities (R(2) > 0.992) and recovery rate (>83%). We used this new method to directly determine the 17 OH-P levels in dried blood specimens from abnormal children of various ages, with a detection limit of 20 ng/ml (approximately 240 pg), to avoid the time-consuming derivatization steps required by the gas-chromatography/mass spectrometry (GC/MS) method. Four dried filter-paper blood samples of CAH patients (three girls and one boy, 1-14 years old) were all quantified in an LC/MS/MS study and revealed high 17 OH-P levels (>90 ng/ml). After treatment, all of the elevated 17 OH-P levels either decreased or disappeared. Compared with CAH patients, 17 OH-P was nearly undetectable (<20 ng/ml) in the normal infants by LC/MS/MS. This LC/MS/MS assay is not only useful for both diagnosis and monitoring of treatment of CAH in all other age groups, it also can be used as a screening test for CAH infants. In this study, we provided the first data on 17 OH-P in dried blood specimens affected with CAH using HPLC/ESI-MS/MS.

17-alpha-Hydroxyprogesterone↗
PubMed2005

Diagnosis of congenital adrenal hyperplasia by rapid determination of 17alpha-hydroxyprogesterone in dried blood spots by gas chromatography/mass spectrometry following microwave-assisted silylation.

17alpha-Hydroxyprogesterone (17OHP) is considered to be the biomarker of congential adrenal hyperplasia (CAH). Screening for CAH in newborns by measuring levels of the biomarker of 17OHP has become routine. In the work, a rapid, simple and sensitive technique was developed for the diagnosis of neonatal CAH by the quantitative analysis of 17OHP in neonatal blood spots. The technique was based on microwave-assisted silylation (MAS) followed by gas chromatography/mass spectrometry (GC/MS). In the method, fast derivatization of 17OHP with N,O-bis(trimethylsilyl)trifluoroacetamide was performed by using microwave irradiation, and the trimethylsilyl derivative thus formed was analyzed by GC/MS. The results of the experiment indicate that MAS followed by GC/MS analysis is a rapid, simple and sensitive method for the determination of 17OHP in blood samples. The proposed technique has been shown to have potential as a powerful tool for the rapid diagnosis of neonatal CAH.

17-alpha-Hydroxyprogesterone↗
PubMed1980

17-hydroxyprogesterone, androstenedione, and testosterone in normal children and in prepubertal patients with congenital adrenal hyperplasia.

To determine maximal plasma levels of androstenedione (A) and testosterone (T) which still can be considered non virilizing in 21-hydroxylase deficiency, we investigated plasma levels of these steroids in unaffected children and in adults. For T we found an upper limit of the prepubertal normal range of 16 ng/dl in girls and of 20 ng/dl in boys, with the exception of boys in the first half-year of life in which T is elevated up to the low adult range with peak values in the 2nd and 3rd month. During puberty T values show a significant difference between pubic hair stage 1 and stage 2. T levels below 20 ng/dl can be considered to be non virilizing. For A we found a plasma concentration of 86 ng/dl to be the upper normal level in both sexes before the onset of puberty. A values below this limit are expected to be non virilizing. To evaluate the usefulness of 17-hydroxyprogesterone (OHP) for the prediction of A and T and to define "acceptable" OHP levels in CAH we performed simultaneous determinations of OHP, T, and A in prepubertal patients treated for CAH. From these values we calculated the 95% confidence interval for prediction of T and A on known OHP levels. On an OHP value of 1.000 ng/dl, T can be expected to be between 6 and 60 ng/dl and A between 25 and 320 ng/dl. Because of these wide ranges, OHP has to be considered an unreliable parameter for predicting androgen levels in CAH.

Adolescent↗
PubMed1988

The effect of hydroxyprogesterone on ureteral stones.

It has been suggested that dilatation of the ureter seen in pregnancy is caused by progesterone. Twenty-four patients with ureteral calculi, therefore, were given an intramuscular injection of 250 mg hydroxyprogesterone in order to facilitate the discharge of the stones. Irrespective of the duration of symptoms there was a potential effect of treatment in up to 66% of the patients. In patients with symptoms of less than three weeks duration the stones were discharged within three weeks after the first symptom in 75% of the cases, which is a much higher incidence rate than that stated in the literature for spontaneous stone discharge (18-30%). In patients with longstanding symptoms 50% of the stones had passed, as compared to 39% reported in the literature. Especially concrements with a diameter larger than 4 mm had a better discharge rate. As the treatment is simple, cheap and without side effects, it seems worthwhile trying it in order to avoid surgery.

Adult↗
PubMedDate not supplied

Effect of gender, birth weight and gestational age on serum 17-hydroxyprogesterone concentration and distribution among neonates in Saudi Arabia.

Blood samples from 813 newborns were spotted on to filter paper and the 17-hydroxyprogesterone concentration was measured using the Delfia (R) fluorometric immunoassay. The median, mean, and standard deviation (SD) for the total population were 20, 21 and (11) nmol/L respectively. Males had significantly higher levels than females with median, mean and (SD) of 22, 22 and (12) nmol/L. Similarly, low birth weight babies were found to have significantly higher levels than normal birth weight babies with median, mean and (SD) of 21, 24 (12) nmol/L. Preterm babies were also found to have significantly higher levels than full term babies, with median, mean and (SD) of 25, 29 (16) nmol/L. As experienced elsewhere, those factors should be taken into consideration when considering a cut-off point in any neonatal screening program for congenital adrenal hyperplasia.

17-alpha-Hydroxyprogesterone↗
PubMed1997

CYP17 gene analysis in hyperandrogenised women with and without exaggerated 17-hydroxyprogesterone response to ovarian stimulation.

Nine patients with polycystic ovary syndrome (PCOS) and exaggerated serum level of 17-hydroxyprogesterone (17-OHP) response to gonadotropin (GnRH) agonist stimulation, and seven patients with PCOS, but normal 17-OHP response have been analysed for possible linkage of PCOS with genetic defects on the 17 alpha-hydroxylase/17,20-lyase gene (CYP17). A portion of the regulatory and the entire coding domain for this enzyme have been analysed by PCR-SSCP analysis. Samples have been also screened for the previously reported -34 bp polymorphism, which creates a new SP1-type promoter site, but was excluded as the primary genetic defect. We have varied gel concentrations, reduced running temperatures, added glycerol to polyacrylamide gels and performed electrophoresis on longer gels in order to improve the resolving power of SSCP. Screening of the CYP17 gene revealed no mutations associated with the disease in the examined group of patients. Also, the -34 bp polymorphism proved to be equally distributed among patient and control samples, which in our case were non-related. The results indicate that, when germline mutations in question, CYP17 may be excluded as a candidate gene for these subtypes of PCOS.

17-alpha-Hydroxyprogesterone↗
PubMedDate not supplied

Neonatal screening for 21-hydroxylase deficiency: a microfilter paper method for 17-alpha-hydroxyprogesterone assay.

A micromethod for measuring 17 alpha-hydroxyprogesterone in blood collected on filter paper has been developed. Our method is rapid, easy and has the specificity, accuracy and precision of the radioimmunoassay in whole blood. The method has been applied for screening patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Fifty samples collected on filter paper were assayed by our method, using 125I as tracer, and results were compared with those obtained for the same samples using a tritium tracer. The agreement between the two methods was particularly good in the area ranging from 15 to 100 pg/disc. In one neonate the diagnosis of CAH was made utilizing the microfilter paper method. Our method is a promising screening test for CAH. An indication of the advantages or disadvantages of this type of screening will become available when an adequate number of infants has been examined.

Adrenal Hyperplasia, Congenital↗
PubMed2005

Adrenal steroids in adrenomyeloneuropathy. Dehydroepiandrosterone sulfate, androstenedione and 17alpha-hydroxyprogesterone.

Adrenoleukodystrophy (ALD) and its adult variant adrenomyeloneuropathy (AMN) are X-linked diseases associated with a deficiency in the peroxisomal degradation of saturated very long chain fatty acids (VLCFA) resulting in an accumulation of VLCFA in the central and peripheral myelin, the adrenal cortex and the testis. Adrenal insufficiency with clinical hypocortisolism occurs in approximately two thirds of the patients with AMN. We studied the circulating adrenal hormones 17alpha-hydroxyprogesterone (17alpha-OHP), androstenedione and dehydroepiandrosterone sulphate (DHEAS) in 63 male AMN patients (age 17-65 years) and the DHEAS serum levels in 95 healthy male controls (age 30-65 years). 34 of the patients presented with the phenotype of only spinal cord and peripheral nerve disability without hypocortisolism, 29 of the patients presented with the phenotype of either additional hypocortisolism or Addison's syndrome only. Normal 17alpha-OHP concentrations were found in all patients with no significant difference between patients without and with hypocortisolism (6.07 +/- 0.61 nmol/l and 4.76 +/- 0.37 nmol/l). Androstenedione concentration was significantly (p < 0.01) lower in patients with hypocortisolism (2.99 +/- 0.65 pmol/l versus 5.71 +/- 0.68 pmol/l). As serum levels of DHEAS are agedependent we divided the two groups into two subgroups each (subgroup one: age 17-40 years, subgroup two: age 41-65 years). The DHEAS concentration of patients without and with hypocortisolism was significantly (p < 0.01) lower in both subgroups (1. 4.35 +/- 0.84 micromol/l, n = 15, 2. 15 +/- 0.28 micromol/l, n = 19; 1. 1.90 +/- 0.57 micromol/, n = 21, 2. 0.96 +/- 0.29 micromol/l, n = 8) compared to controls (1. 9.0 +/- 0.96 micromol/l; 2. 5.21 +/- 0.25 micromol/l). In conclusion, androstenedione and DHEAS serum concentrations are subnormal in all AMN patients and may therefore serve as sensitive markers of the adrenal function in adrenomyeloneuropathy.

17-alpha-Hydroxyprogesterone↗
PubMed1978

Maternal and amniotic fluid 17 alpha-hydroxyprogesterone levels during pregnancy: diagnosis of congenital adrenal hyperplasia in utero.

17 alpha-Hdroxyprogesterone levels (17 alpha-OHP) were measured in 70 samples of amniotic fluid and 30 samples of maternal serum obtained at different stages of normal pregnancy and in samples of maternal serum and amniotic fluid from a pregnancy with the fetus affected with congenital adrenal hyperplasia. The mean level of 17 alpha-hydroxyprogesterone in the amniotic fluid from control pregnancies was 133.9 +/- 7.6 ng. per 100 ml. (range, 25.1 to 266.6 ng. per 100 ml). The levels were significantly higher in midpregnancy (157.4 +/- 8.4 ng. per 100 ml.) than in late pregnancy (79.2 +/- 6.8 ng. per 100 ml.) (p less than 0.01). Amniotic fluid 17 alpha-OHP levels in the affected pregnancy were significantly higher than the control levels. Mean maternal 17 alpha-OHP level during early pregnancy and midpregnancy was 259.5 +/- 22 ng. per 100 ml. and there was a two-to three-fold increase after 37 weeks (672.2 +/- 61 ng. per 100 ml.) The maternal 17 alpha-OHP levels in the affected pregnancy were significantly higher than the control levels after 34 weeks, but before 34 weeks, the level was within the range seen in control pregnancies. Measurement of 17 alpha-OHP levels in the amniotic fluid before 24 weeks and maternal serum after 34 weeks can be utilized for the prenatal diagnosis of congenital adrenal hyperplasia.

Adrenal Hyperplasia, Congenital↗
PubMed1989

Periovulatory female goldfish release three potential pheromones: 17 alpha,20 beta-dihydroxyprogesterone, 17 alpha,20 beta-dihydroxyprogesterone glucuronide, and 17 alpha-hydroxyprogesterone.

Our previous studies have shown that 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) produced by preovulatory female goldfish functions both as a hormone promoting oocyte final maturation and as a primer sex pheromone stimulating rapid reproductive endocrine responses in the male. In the present study, the amounts of free and glucuronated 17,20 beta-P as well as free 17 alpha-hydroxyprogesterone (17P) released to the holding water by female goldfish throughout the periovulatory period were determined. Compared to nonovulating female goldfish, ovulating goldfish released very high levels of each of these steroids. This study confirmed that 17,20 beta-P is released to the water by ovulating fish in sufficient amounts to have pheromonal activity and indicated that 17P may also function as a pheromone. Although considerable quantities of 17,20 beta-P glucuronide were also released, its physiological actions are unknown.

Animals↗
PubMed1983

Progesterone and 20 alpha-hydroxyprogesterone stimulate the in vitro release of GnRH by the isolated mediobasal hypothalamus.

An in vitro perifusion system was used to investigate the effect of progesterone (P4) and 20 alpha-hydroxyprogesterone (20 alpha-OHP) on the release of GnRH from isolated hypothalamic tissue of the adult ovariectomized estradiol-17 beta primed rat. Pulse delivery of P4 stimulated GnRH release not only from the isolated mediobasal hypothalamus-anterior hypothalamus-preoptic area (MBH-AHPOA) complex but also from the MBH alone. Release of GnRH from the MBH was also increased by 20 alpha-OHP. These results suggest that the in vivo increase of circulating P4 or 20 alpha-OHP associated with the initiation of the preovulatory LH surge may play a role in regulating the timing or amplitude of this surge by directly stimulating the release of GnRH from the MBH.

Animals↗
PubMed1975

Radioimmunoassay of progesterone, 17-hydroxyprogesterone, estradiol-17beta and prostaglandin F in human corpus luteum.

Radioimmunoassay procedures have been adapted for the assay of progesterone, 17-hydroxyprogesterone, estradiol-17beta, and prostaglandin F in human corpus luteum. The method utilises a single homogenisation and extraction of the tissue followed by fractionation of the steroids on alumina, and separation of the prostaglandins of the F series from the E and A series on silica gel, prior to radioimmunoassay. An attempt has been made to validate the method for the progestins by comparison with results after fractionation of the progestins on Sephadex LH-20, for estradiol-17beta by comparison with values obtained with competitive protein-binding, and for prostaglandin F by comparison with values after additional purification. The results showed that peak concentrations of the three steroids in corpora lutea from women during the luteal phase of the menstrual cycle were comparable to those found in corpora lutea from women in early pregnancy. However, in six out of fourteen corpora lutea from non-pregnant women, prostaglandin F levels were higher than those found in corpora lutea from seven women in early pregnancy, i.e. 13-46 ng/g compared with 1-7 ng/g. Of the above six corpora lutea, four were on days 23-25 of the cycle, at a time when luteolysis would be commencing. The results in this paper support the conclusion that the corpus luteum is a major site of synthesis of the three steroids examined, although the site of synthesis of prostaglandin F is still equivocal.

Adult↗
PubMed1976

O-(Carboxymethyl)oxime steroidal haptens linked in the C3 position: study of the characteristics of antibodies against 17alpha-hydroxyprogesterone and testosterone and of their evolution with time.

The production of highly sensitive and specific antisera against 17alpha-hydroxyprogesterone (17 OHP) is reported. 17 OHP was rendered antigenic by covalent linkage to bovine serum albumin through position 3 of the steroid. An unambiguous method to prepare the mono-3-0-(carboxy-methyl) oxime derivative (CMO) of 17 OHP is described starting from 17 OHP-acetate. Antisera raised in rabbits were of high affinity for 17 OHP (Ka = 1 to 2 x 10(10) L/mole) and showed very little (less than 0.7%) or no cross reaction with a variety of steroids. Cross-reaction with 17alpha-hydroxy pregnenolone was however significant. When studied in relation to time, cross-reaction of the latter steroid decreased significantly (18 to 2%) while Ka remained at the same level. The same study of the evolution with time (up to 600 days) of the characteristics of antisera raised against the 3 CMO derivative of testosterone is also reported.

Animals↗
PubMed1976

Preparation of 1,2-3H-21-deoxycortisol by incubation of 1,2-3H-17-hydroxyprogesterone with rat adrenal mitochondria.

A method is described for preparation of 1,2-3H-21-deoxycortisol by incubation of 1,2-3H-17-hydroxyprogesterone with rat adrenal mitoochondria. The radiochemical purity of the product was established by two subsequent chromatographies, reversed isotopic dilution and oxidation to 21-deoxycortisone. The final yield of 1,2-3H-21-deoxycortisol was approximately 15%.

17-Hydroxycorticosteroids↗
PubMed1976

Synthesis of 18-substituted steroids Part II (1). Improvements in the preparation of 18-hydroxyprogesterone.

18-Hydroxyprogesterone is conveniently prepared from 3beta-acetoxypregn-5-en-20beta-ol by a modified route. 3beta-Acetoxy-18-iodopregn-5-en-20-one, obtained by the hypoiodite-photolysis procedure and oxidation, is treated with methanolic silver acetate to give the 18, 20-epoxy-20-methoxy derivative, which crystallises directly without need for chromatography. Hydrolysis of the 3-acetate, and a modified Oppenauer oxidation, gave 18-hydroxy-progesterone in 24% over-all yield.

Chemical Phenomena↗