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PubMed1980

Adrenal cortical function in the postmature fetus and newborn infant.

The umbilical venous blood concentrations of cortisol, dehydroepiandrosterone sulfate (DHAS), and unconjugated estriol were compared in 54 normal, 37 postterm, and 22 postmature newborns. Pre- and postadrenocorticotropic hormone (ACTH) stimulation levels of serum cortisol and DHAS were compared in the first 2 to 4 days of life in 19 postterm and 15 postmature infants. Comparison was also made between vaginally an cesarean section delivered postterm and postmature newborns. There were significantly greater cord blood cortisol levels in th postmature [260 +/- 22 ng/ml (+/- S.E.)], than in the normal (193 +/- 11 ng/ml) (P less than 0.01) or postterm (193 +/- 18 ng/ml) (0.01 less than P less than 0.05) vaginally delivered infants. There were no significant differences in the mean cord blood DHAS levels in the three groups (normal, 2645 +/- 130 ng/ml; postterm 2323 +/- 188 ng/ml; postmature, 2310 +/- 224 ng/ml). Cortisol and DHAS responses to ACTH stimulation were the same in the postterm and postmature groups. There was a significantly lower mean umbilical venous unconjugated estriol level in the vaginally delivered postmature group (75 +/- 11 ng/ml) as compared to values in vaginally delivered postterm [120 +/- 14 ng/ml (P = 0.01)] and normal [144 +/- 10 ng/ml (P less than 0.002)] newborns. Stressed postmature infants delivered by cesarean section had higher unconjugated estriol levels (83 +/- 12 ng/ml) than their unstressed, postterm cesarean section controls [40 +/- 9 ng/ml (P less than 0.01)], but levels were still below those from vaginally delivered postterm infants. These findings substantiate normal adrenal function in the postmature fetus and newborn. Lowered umbilical venous unconjugated estriol levels in the postmature infants at birth appear to be a function of limited aromatizing activity of the placenta rather than due to the low levels of fetal adrenal-derived neutral steroid substrate.

Adrenal Cortex↗
PubMed1976

Stimulatory and inhibitory effects of estrogen on uterine DNA synthesis.

The induction of long-term responses in the uterus following estrogen treatment is discussed, with special reference to DNA synthesis. Immature female rats injected daily with estradiol-17beta or estriol (0.01 to 1 mug) or a combination of the two steroids for one, two or three consecutive days were sacrificed at intervals from 12 to 24 h after the last injection of vehicle or steroid. In vitro incorporation of [3H]thymidine into DNA [14C]leucine into protein, and oxidation of [14C)glucose to 14CO2 were determined. Nuclear-bound estradiol was determined by use of exchange assay or following incubation of intact uteri with 1 X 10(-8)M ([3H]estradiol for 1 h at 37 C. Injection of estriol only partially stimulated DNA synthesis by 18 to 24 h post-treatment. However, injection of estriol followed by injection of estradiol 6 h later resulted in increased DNA synthesis, suggesting that estrogen must be present for up to 6 h to induce subsequent DNA synthesis. Maximal DNA and protein synthesis and oxidation of glucose occurred at 24 h after injection of estradiol (0.1 or 1 mug) but was depressed to control levels by 24 h after the last of three daily injections. Daily injections of 0.01 mug of estradiol resulted in a similar pattern of DNA synthesis, although of lesser magnitude than that observed after injection of 0.1 or 1 mug of estradiol. However, if rats receiving daily injections of 0.01 mug estradiol were challenged with a higher dose of estradiol (1 mug), uterine DNA synthesis was markedly increased. The data suggest that prolonged exposure to estrogen causes uterine cells to become metabolically "refractory" to further estrogen stimulation. Sequential injections of estriol (1 mug) or intermittent injections of estradiol (1 mug) were ineffective in causing this uterine "refractoriness". Receptor binding of estrogen, translocation to the nucleus, and retention of receptor in the nucleus were not affected by sequential estrogen treatment. The accumulation of an inhibitory product is suggested as a possible explanation for this phenomenon.

Animals↗
PubMed1999

Equine type estrogens produced by a pregnant woman carrying a Smith-Lemli-Opitz syndrome fetus.

The equine-type estriols 1,3,5(10),7-estratetraene-3,16alpha,17beta-triol (16alpha-hydroxy-17beta-dihydroequilin) and 1,3,5(10),6,8-estrapentaene-3,16alpha,17beta-triol (16alpha-hydroxy-17beta-dihydroequilenin) constituted over half of the estrogens excreted by a woman carrying a Smith-Lemli-Opitz syndrome (SLOS) affected fetus. The steroids were characterized by gas chromatography-mass spectrometry (GC/MS), and mass spectra of the dehydro estriols as trimethylsilyl ethers are illustrated. SLOS is associated with 7-dehydrocholesterol (7DHC), delta 7-reductase deficiency; the enzyme catalyzing the final step in cholesterol biosynthesis. Identification of these equine estrogens show that an estrogen biosynthetic pathway parallel to normal is functional in the feto-placental unit and uses 7DHC as precursor, therefore P450scc, P450c17, and 3betaHSD and P450arom are all active on 7-dehydrometabolites. Patients with affected fetuses have low plasma estriol values (probably due to deficient production of the cholesterol precursor) and this is often a warning sign which instigates further evaluation for SLOS. The estriol deficiency is not quantitatively made up by the dehydrometabolites, and the combined excretion was found to be about one-third of the mean of gestational age matched controls. The importance of these findings lies in the potential value of dehydroestriol measurement for non-invasive diagnosis of SLOS at mid-gestation. Currently diagnosis relies on imaging, since SLOS is a malformation syndrome, and measurement of 7DHC levels in amniotic fluid and chorionic villus tissue.

Adult↗
PubMed1999

Developmental synergism of steroidal estrogens in sex determination.

Gonadal sex in the red-eared slider turtle, Trachemys scripta, is determined by incubation temperature during embryonic development. Evidence suggests that temperature determines sex by influencing steroid hormone metabolism and/or sensitivity: steroidogenic enzyme inhibitors or exogenous sex steroid hormones and their man-made analogs override (or enhance) temperature effects on sex determination. Specifically, nonaromatizable androgens and aromatase inhibitors induce testis differentiation at female-producing temperatures, whereas aromatizable androgens and estrogens induce ovary differentiation at male-producing temperatures. Moreover, natural estrogens and temperature synergize to produce more females than would be expected if estrogens and temperature had purely additive effects on sex determination. In this study, we use sex reversal of turtle embryos incubated at a male-producing temperature to examine synergism among steroidal estrogens: estrone, 17ss-estradiol, and estriol. A low dose of 17ss-estradiol (200 ng) showed significant synergism when administered with a single low dose of estriol (10 ng). Likewise, a single low dose of estrone (250 ng) had a synergistic effect when combined with the same low dose of estriol (10 ng). We conclude that the weak natural estrogens estrone and 17ss-estradiol synergize with a low dose of the more potent estriol to reverse gonadal sex during the critical period of sexual differentiation. These results suggest that weak environmental estrogens may also synergize with stronger natural estrogens.

Animals↗
PubMed1977

[Changes in adrenal gland and thymus induced by sex steroid administration in newborn rats (author's transl)].

Testosterone, dehydroepiandrosterone (DHEA), progesterone, estradiol-17beta, estrone, estriol, 2-hydroxyestradiol-17beta, 2-hydroxyestriol, deoxyestrone and diethylstilbestrol were injected s.c. in a dose of 0.5 mg each into newborn rats on the first day of life, and changes in the adrenal gland, thymus and spleen were examined 3 days later. Increase in the body weight during the 3 days was less in rats treated with DHEA, 2-hydroxyestriol and deoxyestrone, as compared with that in controls. Development of the thymus was significantly impaired in rats injected with various kinds of sex steroids, except progesterone and diethylstilbestrol. Reduction of the spleen weight by sex steroid treatment was not marked. The weight of adrenal gland decreased in rats injected with DHEA and progesterone, while the weight increased in those given estrone and diethylstilbestrol. Estrogens, particularly estriol, induced a marked increase in adrenal corticosterone content, while 2-hydroxyestriol caused only slight elevation and 2-hydroxyestradiol and deoxyestrone had no influence on the content. Suppressive effect of cortisol on the adrenal gland of newborn rats was slightly, but significantly, lessened by estriol treatment. From the results, physiological role of estriol and DHEA in adrenal secretion was discussed.

Adrenal Glands↗
PubMed2006

Is bio-identical hormone replacement therapy safer than traditional hormone replacement therapy?: a critical appraisal of cardiovascular risks in menopausal women.

Recent clinical trials have demonstrated an increase in the risk of cardiovascular disease (CVD) in women using oral hormone replacement therapy (HRT). Bio-identical HRT (BHRT) is widely used by alternative healthcare practitioners for the treatment of symptoms of menopause, with the prevailing assumption that BHRT provides the benefits of HRT while attenuating the risks. However, considering the serious risks of HRT, the use of any form of HRT, including BHRT, without sufficient scientific evaluation may create considerable risk.The main hormone found in BHRT is estriol. Estriol is used alone or in combination with estradiol and estrone. The total daily oral dose of BHRT used is, on average, ten times higher than that used in HRT, and both oral and topical forms are used for bio-identical hormone administration. The clinical trials that have examined cardiovascular outcomes associated with estriol therapy are limited, and there is evidence to demonstrate variable effects on markers associated with cardiovascular risk.Based on the current evidence, the same cardiovascular risks that have recently been found to be associated with oral HRT may also be associated with the administration of oral estriol in BHRT. The use of oral bio-identical hormones cannot be promoted until further evidence is available to demonstrate its safety.

Cardiovascular Diseases↗
PubMed1980

Changes in serum hormone levels during labor induced by oral PGE2 or oxytocin infusion.

The hormonal changes in maternal serum during parturition induced by amniotomy and oxytocin (OXY) infusion or oral prostaglandin E2 (PGE2) medication have been compared in 68 patients (33 women in the PGE2 group, 35 in the oxytocin group). The effect of PGE2 differed from that of oxytocin. Thus the prostaglandin elicited increases in total estriol (p < 0.001) and decreases in prolactin (p < 0.01), TSH (p < 0.05) and HPL (p < 0.05) from the basal level to that immediately before parturition. Maternal serum cortisol levels rose to the same extent in both treatment groups (p < 0.001). The significant (p < 0.05) increase occurred earlier among women receiving PGE2 (two hours into therapy), even though labor pain was experienced later in this group. The serum estriol elevation in these patients was significant three hours after start of therapy (p < 0.05). A similar time course was noted for the decrease of serum prolactin in PGE2 treated patients. The drop in maternal serum levels of HPL and TSH in the PGE2 group was significant only immediately prior to partus. Neither PGE2 nor oxytocin induced changes in maternal serum levels of HCG or alpha-fetoprotein or estradiol. Oxytocin but not PGE2 lead to a decrease in maternal serum progesterone concentrations; this was significant (p < 0.05--p < 0.01) only late in labor. Mixed umbilical serum levels of the hormones mentioned above were the same regardless of method of induction. Hence the increased maternal estriol concentrations during PGE2 treatment were not reflected in fetal blood. It is suggested that increases in maternal estriol levels during PGE2 medication are due to effects on the maternal enterohepatic circulation rather than on the fetoplacental unit. Irrespective of maternal treatment umbilical serum from female newborns contained statistically higher (p < 0.05) levels of estradiol and HCG than serum from male children.

Administration, Oral↗
PubMed1980

Effects of salt extraction on the quantitation of nuclear estrogen receptors: interference by secondary estrogen binding sites.

The effects of salt-extraction on type I and type II estrogen binding sites were examined in uterine nuclei. Injection (10 ug) of estradiol or estriol in adult ovariectomized rate induced maximum numbers (80-100%, integral of 1 pmole/uterus) of 0.4 M KCL resistant type I estrogen complexes at 1 hour. Only estradiol, which sustained these levels for long periods of time (4-24 hours) stimulated true uterine growth. Likewise, a single injection of estradiol, but not estriol, also elevated nuclear type II sites throughout the entire uterine growth period (1 - 48 hours). However extraction of these nuclei from estradiol injected rats with 0.4 M KCL increased the numbers of type II sites from integral of 1 pmole/uterus (non-extracted nuclei) to integral of 8 pmoles/uterus (salt resistant plus salt-extractable fractions). Sixty percent of these sites were resistant to salt-extraction. Continuous exposure to either estradiol or estriol by beeswax implants stimulated nuclear type II sites which were highly resistant (80%) to KCL-extraction, and additional sites were not exposed by high salt. Thus chronic treatment with both estrogens "locked in" nuclear type II sites such that they were resistant to KCL-extraction. This resistance of type II sites to salt-extraction correlated with the ability of estradiol and estriol implants to stimulate true uterine growth. The procedures presented here for nuclear preparation and assay have reduced non-specific binding considerably in the uterine system, and may eliminate the need to perform exchange assays on salt-extracted nuclei in other systems.

Animals↗
PubMed2001

Physiological effects of shift work on hospital nurses.

OBJECTIVE: The purpose of this study was to assess the physiological effects of shift work on the urinary excretion rates of norepinephrine, 6-sulfatoxymelatonin and estriol in hospital nurses. METHOD: Twenty-four hour urine specimens were examined on a daytime/nighttime basis for each work shift of pregnant and non-pregnant subjects. The urinary norepinephrine and 6-sulfatoxymelatonin were measured by enzyme-linked immunosorbent assay and estriol by radio-immunoassay. RESULTS: Urinary norepinephrine level during the night work was higher than the night levels of the days off and the day shift. Urinary 6-sulfatoxymelatonin level during the night work was lower than the night levels of the days off and the day shift. Urinary estriol level of pregnant subjects showed no differences among work shift and also between daytime and nighttime. CONCLUSIONS: Urinary excretion rates of norepinephrine and 6-sulfatoxymelatonin were affected by shift work both for non-pregnant and pregnant subjects. It was unlikely that urinary estriol levels in the pregnant subjects were significantly affected by shift work.

Adult↗
PubMed1978

Effect of calcium on in vitro contractility of human umbilical artery.

The action of calcium on human umbilical artery was studied by an in vitro perfusion method. An increase in tonus and intense spontaneous activity were observed in the preparations at high calcium concentrations. A marked relaxation of the umbilical artery occurred in the absence of calcium. Estriol had a relaxing effect on the umbilical vessels which was more intense at calcium concentrations near physiological levels. Estriol also abolished spontaneous contractions. In the absence of calcium, estriol showed no relaxing effect. The results suggest a participation of calcium in the mechanism of action of estriol on human umbilical artery in vitro.

Calcium↗
PubMed1977

A semi-automated fluorometric method for total estrogens in pregnancy urine.

We report a continuous-flow fluorometric method for total urinary estrogens that involves the Kober reaction, with extraction of the reaction product into dichloroethane containing trichloroacetic acid as described by Hahnel and Jones [Clin. Chim. Acta 16, 185 (1967)]. The dichloroethane extraction gives greater stability to the Kober color and sharper separation of aqueous and organic phases. The analytical system is adjusted to give maximum response to estriol 16alpha,beta-D-glucuronide, the principal estrogen conjugate in urine from late pregnancy, when calibrated with estriol standards. An initial 20-fold dilution of the sample with water increased analytical recovery of estriol conjugates from urine while maintaining adequate fluorescent response. Glucose interference was reduced by dilution and eliminated by treatment with sodium borohydride. Urinary protein up to 20 g/liter did not interfere. Total estriol, as determined by gas-liquid chromatography, comprises about 70% of total urinary estrogens in late pregnancy as measured by our continuous-flow fluorometric method. A reference range is presented based on 209 randomly collected urine specimens in which total urinary estrogens are expressed as a ratio to creatinine.

Chromatography, Gas↗
PubMed1994

Role of diet on the enterohepatic recycling of estrogen in women taking contraceptive pills.

The effect of diet on the enterohepatic recycling of estrogen after oral administration of 1 mg non-radioactive estriol (E3) was studied in six women using contraceptive pills. The women were followed for two consecutive menstrual cycles, firstly on a high fibre diet (HFD) and then changing on to low fibre diet (LFD) during the next cycle, hence each subject acted as its own control. The extent of enterohepatic recycling of estriol (E3) during the early follicular phase of menstrual cycle was assessed by monitoring during 48 hours, the urinary excretion of its two major metabolites, i.e., estriol-3-qlucuronide (E3-3-G) and estriol 16 alpha-glucuronide (E3-16 alpha-G). An increase in values of the variables including E3-3-G/E3-16 alpha-G output ratio, E3-3-G output as % of total (E3-3-G+E3-16 alpha-G) excretion and total E3 (E3-3-G+E3-16 alpha-G) output as % dose was noted as a result of change from high to low fibre diet. The urinary excretion of E3 in the form of its metabolites was also delayed as a result of dietary change. These findings reveal that extent of enterohepatic recycling of estrogen containing contraceptives could be higher in women on LFD as compared to those who are on HFD.

Adult↗
PubMed1977

[Bilirubin level and estrogen elimination in newborns (author's transl)].

Free estradiol and estriol was determined radioimmunologically in cord blood and in peripheral venous blood during the third, fifth and seventh day of life. The steroid level of a group of children with icterus neonatorum simplex were compared with an anicteric control group. In spite of the higher level of estriol in cord blood during the first week of life, estriol was eliminated much more rapidly than estradiol and independent of the bilirubin level. Given the same initial values for estradiol in cord blood of both control groups, the estradiol elimination rate was significantly slower in icteric newborns. The level of estradiol in cord blood was significantly higher in newborn males than in newborn females. A higher level in cord blood, however, does not increase the risk of a later newborn hyperbilirubinemia. Our findings tend to indicate that no etiologic importance should be attached to the amount of estradiol and estradiol to be eliminated, for the development of icterus neonatorum simplex. At the same time, icteric newborns have a relative insufficiency in estradiol elimination but not, however, in estriol elimination.

Bilirubin↗
PubMed2006

The chick embryo: an animal model for detection of the effects of hormonal compounds.

Hormonal compounds are a class of pharmaceutical product that disrupt the endocrine system of animals and humans. Exposure to these molecules, even at low concentrations, can have severely damaging effects on the environment, to organisms, and to humans. The cumulative presence of these compounds is also characterized by synergistic effects which are difficult to estimate. They are an underestimated danger to the environment and to the human population. This paper presents an in-vivo model enabling to assessment of the real impact of exposure to hormonal compounds and the synergistic effect which can be involved. The anatomical effects of in-ovo exposure to two natural estrogen compounds (estrone and estriol, at 600 ng g(-1)) and a synthetic estrogen (ethynylestradiol, at 20 ng g(-1)) have been investigated. Estrone and estriol lead to morphological defects, mainly in the urogenital system of the developing chick embryo, whereas ethynylestradiol has fewer effects. Estriol caused persistence of Müllerian ducts in 50% of male embryos and hypertrophic oviducts in 71% of females. Estrone had the same effects but at the percentages were lower. Kidney dysfunction was also observed, but only with estrone, in both males and females. We also tested estrogenic compounds in two types of cell line which are estrogen sensitive (BG1 and MCF7) then completed and confirmed our previous in-vivo results. Seven pharmaceutical-like compounds--estrone (E1), estradiol (E2), estriol (E3), ethynylestradiol (EE(2)), carbamazepine (C), genistein (G), and bisphenol-A (BPA)--were tested alone or in mixtures. Different effects on the two cell lines were observed, indicating that endocrine compounds can act differently on this organism. Experiments also showed that these molecules have synergistic action and induce more severe effects when they are in mixtures.

Animals↗
PubMed1982

Effects of estradiol-17 alpha on nuclear occupancy of the estrogen receptor, stimulation of nuclear type II sites and uterine growth.

Estriol and estradiol-17 alpha (E2-17 alpha) have classically been described as weak or impeded estrogens since they are incapable of stimulating true uterine growth when administered acutely by single injection. We have demonstrated [16] that estriol is capable of stimulating true uterine growth when the hormone is administered by paraffin implant. The possibility that E2-17 alpha is similar to estriol was examined. A single injection of E2-17 alpha causes a rapid accumulation of the estrogen receptor in uterine nuclei and this is correlated with the stimulation of early uterotropic responses. The nuclear receptor content declines rapidly and no stimulation of nuclear type II sites or true uterine growth is observed. E2-17 alpha does however stimulate the replenishment of cytoplasmic estrogen receptor. This receptor-response profile is typical of a short acting estrogen such as estriol. Chronic exposure (96 h) of mature-ovariectomized rats to estradiol-17 alpha (4 mg) by beeswax implant results in continual nuclear occupancy by estrogen receptors, dramatic stimulation of nuclear type II sites and true uterine growth. It is not possible to determine whether the uterotropic stimulation was due to direct effects of E2-17 alpha since this isomer was partially metabolized to E2-17 beta and both isomers were found in uterine nuclei after an implant of E2-17 alpha. We conclude that E2-17 alpha is capable of acting as an estrogen, either by its inherent estrogenicity or by its conversion to E2-17 beta, and that it may be dangerous to consider this steroid to be an ineffective or inadequate estrogen.

Animals↗
PubMed2005

Monitoring of natural and synthetic hormones in a polluted river.

Natural (estradiol, estrone, testosterone, estriol) and synthetic hormones (ethinylestradiol) are constantly excreted into the environment from human and animal sources but little is known of their transport. The purpose of this study was to determine how far along a 100 km river course that hormones could be detected after contamination with sewage effluent or fishpond effluent. Fourteen sites in the Lower Jordan River drainage were sampled (two sites above the sewage effluent contamination, eight sites below the contamination and four tributaries) before and after the dry season of 2002 (Spring and Fall). Samples were tested for testosterone, estrogen (estrone and estradiol combined), estriol, ethinylestradiol, ammonia and fecal coli. It was found that the fecal coli count dropped exponentially (from 250,000 to 60/100 ml3) and the ammonia dropped from 15 to less than 1mg/l over the initial 25 km stretch. Over the same stretch, the hormone values declined by half from their maximum values for testosterone (3.3 ng/l), estriol (8.8 ng/l), ethinylestradiol (6.1 ng/l), and estrogen (4.9 ng/l). From 67 to 100 km mark, testosterone (4.8 ng/l) and estrogen (2.4 ng/l) were still elevated while ethinylestradiol and estriol were >or=1.5 ng/l. The high level of testosterone and estrogen between 67 and 100 km marks was probably due to major discharge from fishponds between 23 and 27 km marks. Levels of ethinylestradiol above 1 ng/l, a level which can affect fish, was seen in 70% (12/16) of the samples tested. The data suggest that hormones in readily measured quantities can be transported considerable distances from the source of pollution.

Environmental Monitoring↗
PubMed2006

Biophysical characterization of the sterol demethylase P450 from Mycobacterium tuberculosis, its cognate ferredoxin, and their interactions.

Mycobacterium tuberculosis encodes a P450 of the sterol demethylase family (CYP51) chromosomally located adjacent to a ferredoxin (Fdx). CYP51 and Fdx were purified to homogeneity and characterized. Spectroscopic analyses were consistent with cysteinate- and aqua-ligated heme iron in CYP51. An epsilon419 of 134 mM(-1) cm(-1) was determined for oxidized CYP51. Analysis of interactions of 1-, 2-, and 4-phenylimidazoles with CYP51 showed that the 1- and 4-forms were heme iron-coordinating inhibitors, while 2-phenylimidazole induced a substrate-like optical shift. The 2-phenyimidazole-bound CYP51 demonstrated unusual decreases in high-spin heme iron content at elevated temperatures and an almost complete absence of high-spin heme iron by low-temperature EPR. These data suggest thermally induced alterations in CYP51 active site structure and/or binding modes for the small ligand. Reduction of CYP51 in the presence of carbon monoxide leads to formation of an Fe(II)-CO complex with a Soret absorption maximum at 448.5 nm, which collapses (at 0.246 min(-1) at pH 7.0) forming a species with a Soret maximum at 421.5 nm (the inactive P420 form). The rate of P420 formation is accelerated at lower pH, consistent with protonation of the cysteinate (Cys 394) to a thiol underlying the P450-P420 transition. The P450 form is stabilized by estriol, which induces a type I spectral shift on binding CYP51 (Kd = 21.7 microM). Nonstandard spectral changes occur on CYP51 reduction (using either dithionite or natural redox partners), including a blue-shifted Soret band and development of a strong feature at approximately 558.5 nm, suggestive of cysteine thiol ligation. Thus, ligand-free ferrous CYP51 is prone to thiolate ligand protonation even in the absence of carbon monoxide. Analysis of reoxidized CYP51 demonstrates that the enzyme re-forms P450, indicating that Cys 394 thiol is readily deprotonated to thiolate in the ferric form. Spectroscopic analysis of Fdx by EPR (resonance at g = 2.03) and magnetic CD (intensity for oxidized and reduced forms and signal intensity dependence on field strength and temperature) demonstrated that Fdx binds a [3Fe-4S] iron-sulfur cluster. Potentiometric studies show that the midpoint potential for ligand-free CYP51 is -375 mV, increasing to -225 mV in the estriol-bound form. The Fdx potential is -31 mV. Fdx forms a productive electron transfer complex with CYP51 and reduces it at a rate of 3.0 min(-1) in the ligand-free form and 4.3 min(-1) in the estriol-bound form, despite a thermodynamic barrier. Steady-state analysis of a M. tuberculosis class I redox system comprising flavoprotein reductase A (FprA), Fdx, and estriol-bound CYP51 indicates heme iron reduction as a rate-limiting step.

Amino Acid Sequence↗
PubMed2003

Accuracy of fetal growth indicators as surrogate measures of steroid hormone levels during pregnancy.

This study evaluates the use of fetal growth characteristics as surrogate measures for steroid hormone exposures during pregnancy. The validity of using birth weight, birth length, ponderal index, and placental weight as indicators of pregnancy hormone exposures was assessed using third-trimester serum samples from 568 pregnant women who participated in the Child Health and Development Studies, Berkeley, California (1959-1966). The magnitude of the associations between birth characteristics and hormone concentrations was assessed using geometric means, Pearson's correlations, and linear and logistic regression. Accuracy was evaluated using sensitivity, specificity, and receiver operating characteristic curve analyses. The strongest and most consistent association observed was between birth weight and estriol levels. Despite a positive correlation (r = 0.32) and strong associations with high estriol levels (odds ratio for highest compared with lowest birth weight quartile = 6.63, 95% confidence interval: 3.20, 12.5), the predictive performance of birth weight as a proxy for estriol levels was poor (area under the receiver operating characteristic curve = 0.66, 95% confidence interval: 0.61, 0.71). Likewise, all fetal growth measures revealed little discriminatory ability as indicators of estriol, estrone, estradiol, or progesterone levels. Thus, observed associations with these surrogate measures may not be a reflection of pregnancy hormone exposure and should be interpreted with caution.

Biomarkers↗