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PubMed2005

Effects of estrogens on cardiovascular structure in uninephrectomized SHRsp rats.

BACKGROUND: The risk of cardiovascular disease in uremic patients is greater in male than in female patients. Estrogens seem to play a cardioprotective role until menopause. Experimental data on the effect of estrogens on cardiovascular damage are controversial and potential underlying mechanisms especially in renal failure have not been fully clarified. METHODS: Three-month-old female uninephrectomized stroke-prone spontaneously hypertensive (SHRsp) rats were sham-operated or ovariectomized. Subsequently, they received either vehicle (sesame oil) or 17-beta-3 benzoate estradiol (E2) (25 microg/day) or estriol (E3) (0.02 mg/day), respectively. After 3 months the animals were sacrified and the organs were harvested using pressure-controlled perfusion fixation. Stereologic parameters such as capillary length density (L(V)), mean intercapillary distance (MID), and volume density of the interstitial tissue (Vv) were quantitated. Additionally, expression of transforming growth factor-beta (TGF-beta), vascular endothelial growth factor (VEGF), flt-1, endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), endothelin A receptor (ETA) receptor, and alpha estrogen receptor was assessed using immunohistochemistry. Intramyocardial capillaries and the aorta were investigated by morphometric methods. RESULTS: L(V) (mm/mm(3)) was significantly lower (2421 +/- 500) and MID (microm) significantly higher (22.2 +/- 2.33) in vehicle-treated uninephrectomized/ovariectomized compared to uninephrectomized/sham-ovariectomized controls (L(V) 3629 +/- 960, MID 12.7 +/- 2.7) as well as estradiol (L(V) 3340 +/- 739, MID 12.1 +/- 4.96) and estriol (L(V) 4655 +/- 618, MID 14.2 +/- 2.89) treated uninephrectomized/ovariectomized animals. The volume density of the cardiac interstitium was higher in vehicle-treated uninephrectomized/ovariectomized animals compared to uninephrectomized/sham-ovariectomized, estradiol and estriol treated uninephrectomized/ovariectomized rats. The protein level expression of TGF-beta was higher in vehicle treated uninephrectomized/ovariectomized compared to uninephrectomized/sham and all treatment groups. CONCLUSION: In ovariectomized SHRsp rats with moderate renal failure cardiac lesions were strikingly less after estradiol or estriol treatment. The results document a beneficial role of estrogens on cardiac abnormalities in a model of moderate renal dysfunction.

Animals↗
PubMed2004

The unusual binding properties of the third distinct teleost estrogen receptor subtype ERbetaa are accompanied by highly conserved amino acid changes in the ligand binding domain.

Three forms of estrogen receptor: ERalpha, ERbeta (ERbetab), and a second ERbeta, ERbetaa (formerly ERgamma) are present in teleost fish. All ERbetaas share amino acid changes in the ligand binding domain that may influence ligand specificity and receptor function. We compared binding specificities of the three ERs of the teleost fish, Atlantic croaker Micropogonias undulatus. Bacterially expressed Atlantic croaker (ac) ERalpha, -betab, and -betaa fusion proteins showed specific, high affinity binding to 17beta-[(3)H]estradiol, with K(d) values of 0.61 +/- 0.013, 0.40 +/- 0.006, and 0.38 +/- 0.059 nm, respectively. Rank orders of binding were: diethylstilbestrol >> ICI182780 > 4-hydroxytamoxifen > ICI164384 > estradiol >/= zearalenone > moxestrol > tamoxifen > estrone >/= 17alpha-estradiol > estriol > 2-hydroxyestrone = genistein >> RU486 for acERalpha; ICI182780 > diethylstilbestrol > 4-hydroxytamoxifen > estradiol > ICI164384 > genistein > moxestrol > tamoxifen > zearalenone = estrone > estriol = 17alpha-estradiol > 2-hydroxyestrone >> RU486 for acERbetab; and estradiol >/= diethylstilbestrol > 4-hydroxytamoxifen > ICI182780 > ICI 164384 > estriol >/= genistein > moxestrol > zearalenone > estrone > 17alpha-estradiol > RU486 >/= tamoxifen > 2-hydroxyestrone for acERbetaa. acERbetaa showed higher relative binding affinities for estradiol, estriol, and RU486 and lower relative binding affinities for synthetic estrogens and antiestrogens than previously characterized ERs. Mutation of the conserved teleost substitutions (acERbetaaPhe(396)) to the ERalpha or ERbetab counterpart shifted diethylstilbestrol and tamoxifen affinities toward those of wild-type acERalpha and acERbetab, supporting the hypothesis that the positions with conserved residue changes in teleost ERs are important to ER structure and function.

Amino Acid Sequence↗
PubMed2002

Reduced 11beta-hydroxysteroid dehydrogenase type 2 activity is associated with decreased birth weight centile in pregnancies complicated by asthma.

Pregnancies complicated by asthma are associated with an increased risk of low birth weight. Currently, the mechanisms causing this outcome are unknown. To investigate whether impaired placental function may be a determinant, we measured placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity, protein and mRNA, placental CRH mRNA, fetal cortisol, and fetal estriol concentrations at delivery. Asthmatic subjects were classified according to inhaled glucocorticoid intake during pregnancy and compared with a control nonasthmatic group. There was a 25% reduction in neonatal birth weight centile in asthmatic women who did not use inhaled glucocorticoid treatment. This was accompanied by significantly reduced placental 11beta-HSD2 activity, significantly increased fetal cortisol, and a trend toward increased placental CRH mRNA and reduced fetal estriol concentrations. The use of inhaled glucocorticoids for treatment was associated with birth weight centile, 11beta-HSD2 activity, CRH mRNA, fetal cortisol, and estriol concentrations similar to control levels. There was a significant inverse correlation between fetal cortisol and fetal estriol concentrations across all groups. These studies demonstrate that inhaled glucocorticoid intake for the treatment of asthma is associated with improved placental function and fetal outcome, suggesting that inflammatory factors associated with asthma may be detrimental to fetal growth and development in these pregnancies.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed1975

[Study on metabolic pathway from dehydroepiandrosterone sulfate to estrogen in late pregnancy (author's transl)].

To investigate the metabolic pathway from dehydroepiandrosterone sulfate (DHAS) to estriol (E3) in late human pregnancy, DHAS (50 to 100 mg) was given intravenously or intraamniotically to 13 volunteers (from cases of normal pregnant women, pregnant women with a live anencephalic fetus, intrauterine fetal death or hydatidiform mole and a patient complicated with cancer of the cervix). Urinary estrogens, serum unconjugated estrogens and urinary dehydroepiandrosterone (DHA) and 16alpha-hydroxy-dehydroepiandrosterone (16alpha-OH-DHA) were measured before and after injection. Brown's method (1955) has been used to measure urinary three fractions of estrogens, estrone (E1), estradiol (E2) and estriol (E3). Serum unconjugated estrogens, estrone (SE1), estradiol (SE2) and estriol (SE3) were determined by a radioimmunoassay technique (a modification of the method of Makino, 1973). Urinary DHA and alpha-OH-DHA were separated by a modification of the method of Lakshmanan and Lieberman (1954) and by thin layer chromatography, and estimated by the method of Oertel and Eiknes (1959). Results obtained were as follows: (1) In seven cases of pregnancy with a live anencephalic fetus the excretion of urinary estriol was very low and the ratio of E3/E1+E2 was much less than that in normal pregnancy. (2) In five women with a live anencephalic fetus the effect of intravenously injected DHAS was studied. In each case there was a remarkable in urinary E3, E1 and E2, while no remarkable difference between the ratio of E3/E1+E2 before and after administration of DHAS was found. (3) DHAS was given intraamniotically to two women with a live anencephalic fetus. A greater rise of the ratio of E3/E1+E2 after administration of DHAS was found, compared to the control. (4) DHAS circulating in the maternal organism is converted to E3 largely via a phenolic pathway (DHAS-E1-E3), whereas DHAS circulating within the feto-placental compartment is converted to E3 via both phenolic and neutral intermediates (DHAS-16alpha-OH-DHAS-E3). (5) The ratio of urinary 16alpha-OH-DHA/DHA in pregnancy with a live anencephalic fetus was greater than that in non-pregnant woman. This suggests that 16alpha-hydroxylase activity in pregnancy is elevated. (6) Increases in serum unconjugated E1, E2 and E3 after intravenous administration of DHAS in three pregnant women with a live anencephalic fetus were found.

Adult↗
PubMed1993

Effect of rifampicin on the enterohepatic recycling of estrogen in female tuberculous patients.

Enterohepatic recycling of estrogen after oral administration of 1 mg non-radioactive estriol was studied in ten women taking rifampicin as one of the antitubercular drugs and in fourteen healthy women selected as control subjects. The extent of enterohepatic recycling of estriol (E(3)) during early follicular phase of menstrual cycle was assessed by monitoring for 48 hours the urinary excretion of its two major metabolites i.e., estriol-16alpha-glucuronide (E(3)-16alpha-G) and estriol-3-glucuronide (E(3)-3-G). Of these metabolites the former is synthesized in liver as well as in the gut where as later is synthesized exclusively in the gut, hence the change in urinary level of H(3)-3-G with respect to E(3)-16alpha-G was considered to reflect the extent of enterohepatic recycling of E(3). The levels of both metabolites in urine were determined by radioimmunoassay. Lower values of variables including E(3)-3-G output, E(3)-3-G output as % of the total (E(3)-16alpha-G + E(3)-3-G) excretion and total E(3) (E(3)-16alpha-G + E(3)-3-G) output as % dose and the diurnal variation in urinary excretion of these metabolites show that the final elimination of E(3) from the body was quicker in these patients as compared with the control subjects, probably due to the reduced extent of enterohepatic recycling of E(3) as a result of long term chemotherapy with rifampicin.

Journal Article↗
PubMed1991

A maternal serum screen for trisomy 18: an extension of maternal serum screening for Down syndrome.

The feasibility of extending second-trimester maternal blood screening for Down syndrome so as to include screening for trisomy 18 was examined using stored maternal serum samples collected for neural tube-defect screening. There were 12 samples from trisomy 18 pregnancies and 390 controls. The median maternal serum concentration of alpha-fetoprotein, free alpha-subunit human chorionic gonadotrophin, free beta-subunit human chorionic gonadotrophin, intact human chorionic gonadotrophin, total estriol, unconjugated estriol, estradiol, human placental lactogen, and progesterone were lowered in those pregnancies affected by trisomy 18 when compared with unaffected pregnancies matched for racial origin, maternal age, gestational age, and sample-storage duration. At an estimated odds risk of 1:400, 83.3% of affected pregnancies were detected using an algorithm which combines the maternal age-related risk with the maternal serum concentrations of unconjugated estriol, free alpha-subunit human chorionic gonadotrophin, free beta-subunit human chorionic gonadotrophin, estradiol, and human placental lactogen. The associated false-positive rate was 2.6%. At high risk odds of 1:10, the detection rate was 58.3%, with an associated false-positive rate of 0.3%. beta-Subunit human chorionic gonadotrophin and unconjugated estriol were the most powerful discriminators. It is possible to incorporate into existing Down syndrome screening programs an algorithm for detecting trisomy 18 with high sensitivity and specificity.

Adult↗
PubMed1987

Skin absorption and cutaneous first pass metabolism of topical steroids: in vitro studies with mouse skin in organ culture.

Using mouse skin maintained in a permeability chamber-organ culture system, we have examined the percutaneous penetration and cutaneous fate of some selected steroids. At 16 hr after in vitro topical application (10 micrograms/2 cm2), the extent of permeation of the selected steroids was testosterone (65.13%) much greater than cortisol (18.1%) = estradiol (18.0%) greater than estrone (10.58%) much greater than estriol (2.45%). Permeation was accompanied by cutaneous first pass metabolism. In addition to water-soluble metabolites, other metabolites found in the perfusion medium from topical testosterone included 5 alpha-dihydrotestosterone, 5 alpha-androstanedione and androstenedione. Cortisone was identified as one of the metabolites of topical cortisol. For the estrogens, estradiol and estriol were metabolites of topical estrone, whereas estrone and estriol were metabolites of topical estradiol. The extent of cutaneous first pass metabolism of these selected steroids varies considerably. Estrone was metabolized extensively, but only limited metabolism of estradiol and cortisol was observed during their translocation through the skin. With testosterone, it was evident that an increase in the topically applied dose was accompanied by a decrease in the relative extent of both permeation and cutaneous first pass metabolism. However, cutaneous first pass metabolism of estriol was essentially negligible. These observations demonstrated that both diffusional and metabolic processes are important in the percutaneous fate of topical steroids. They also suggest that in future studies concerned with the absorption and bioavailability of topically applied chemicals, an assessment of the drug-metabolizing capabilities of the skin needs to be considered.

Administration, Cutaneous↗
PubMed1986

[Prenatal diagnosis and treatment of intrauterine growth retardation].

A diagnosis of intrauterine growth retardation (IUGR) was made in 150 pregnancies on the basis that the estimated fetal body weight was less than -1.5 SD of the intrauterine growth curve for the Japanese population in two consecutive measurements. The estimation of fetal body weight was made from the biparietal diameter and abdominal circumference using the formula of Shepard et al. Maternal plasma estriol, urinary estriol and plasma hPL were determined, and routine instructions to take daytime bedrest and a high protein diet were made. 75 optionally selected cases were given oral allylestrenol 30 mg/day until the time of delivery (the medicated group), and the other 75 cases (control group) were given no medication. Ultrasonic and biochemical measurements were repeated every two weeks thereafter. The estimated fetal weight calculated from Shepard's formula was of sufficient accuracy to make it possible to predict the fetal weight before delivery. In the control group, the estimated fetal weight averaged 1,281 grams at the initial measurements at an average of 32.7 weeks' gestation when the diagnosis of IUGR was made, and 2,498 grams at the final measurements at an average of 38.7 weeks gestation immediately before delivery. In the medicated group, the estimated fetal weight averaged 1,242 grams at the initial measurements at 32.8 weeks' gestation, and 2,826 grams at the final measurements at 39.0 weeks' gestation. Statistically significant increases in the fetal body weight were noted in the medicated group. Maternal plasma estriol, urinary estriol and plasma hPL concentrations rose significantly in the medicated group when compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Allylestrenol↗
PubMed1981

Steroid D-ring glucuronides: characterization of a new class of cholestatic agents in the rat.

Estriol-17 beta(beta-D-glucuronide) (E317G), estriol-16 alpha(beta-D-glucuronide) (E316G) and testosterone-17 beta(beta-D-glucuronide) (TG) produced an immediate, reversible and dose-dependent inhibition of bile flow after their i.v. administration in the rat. Within 15 to 30 min of their administration, bile flow was inhibited by 50% at doses of 13.2, 20.0 and 31.6 mumol/kg of E317G, TG and E316G, respectively. A plot of the logarithm of the dose of each agent vs. the maximal percentage of inhibition of bile flow yielded straight lines which were parallel. E317G, TG and E316G were 0.68, 0.40 and 0.29 times as potent, respectively, as estradiol-17 beta(beta-D-glucuronide), a previously identified cholestatic steroid glucuronide. Maximal inhibition of bile acid secretory rate was similar to that of bile flow for all three agents. Calculation of the bile acid vs. bile flow regression lines indicated substantial inhibition of bile acid independent flow by E317G and TG but only slight inhibition by E316G. In contrast, estriol-3(beta-D-glucuronide) at doses of 11 and 33 mumol/kg increased bile flow. After an i.v. dose (44 mumol/kg) of [3H]E316G, 53% of the dose was recovered in the bile in 3 hr. Unchanged [3H]E316G and a minor metabolite tentatively identified as [3H]estriol-3-sulfate-16 alpha(beta-D-glucuronide) were the predominant compounds recovered in the bile. These data present evidence for a new class of cholestatic compounds, the steroid D-ring glucuronides, and suggest a means by which endogenous or exogenous steroids may produce hepatobiliary dysfunction.

Animals↗
PubMed1996

[The effect of electrotranquilization on the hormonal indices of alcoholic patients].

The correlation between clinical signs of alcoholism dynamics and hormonal status indices was analysed in 26 patients during medical electrotranquilization sessions. Electrotranquilization (ET) was carried out by "Lénar" (Russia) apparatus. There were estimated the concentrations of the following hormones: adrenocorticotropic hormone, hydrocortisone, prolactin, follicle stimulating, luteinizing hormones, estriol, testosterone, somatotropic, thyrotropic hormones, triiodothyronine, tyrosine and insulin. The inverse correlation was observed between the estriol, testosterone and tyrosine levels on the one hand and the clinical signs of the reaction to alcohol administration on the other hand. So far as the disease severity strengthened, both the elevation of estriol and the decrease of testosterone levels were observed. The prolactin concentration correlated directly with meta-alcoholic clinical signs gravity. This confirmed the prolactin role both in postalcoholic haemostasis restoration and in pathogenesis of meta-alcoholic clinical signs. In alcoholic patients the ET normalized the serum prolactin level as well as promoted the trend to normalization of estriol and testosterone levels.

Adult↗
PubMed1979

The role of ligand-binding as a determinant of the structure and activation of the estrogen receptor.

The dissociation of estradiol from the estrogen receptor occurs in two kinetic phases: a fast component having a half-time of approximately 3 min and a slower, or second, dissociating component having a half-time of approximately 95 min at 28 degrees. The fast component is produced by the dissociation of estradiol from the nonactivated 4 S receptor, a monomer. Thus, the magnitude of the fast component of the [3H] estradiol biphasic dissociation curve is proportional to the fraction of the receptor in the nonactivated state. The slow component is the estradiol dissociating from the activated 5 S receptor, a dimer. The salt-extracted estrogen receptor isolated from uterine nuclei shows a single, slow dissociating component equal to the slower component of the cytoplasmic biphasic dissociation curve. Estradiol binding shifts the receptor equilibrium from the low affinity nonactivated 4 S receptor toward the high affinity activated 5 S receptor. The kinetics of estriol dissociation from the receptor shows a larger fractional magnitude for the fast component and a faster second dissociating component than estradiol. This suggests that estriol transforms a smaller fraction of the receptor to the activated state and that the activated estriol receptor has a shorter half-time than estradiol. The biphasic dissociation kinetics of an estrogen from the receptor provides a new and sensitive criterion for measuring receptor activation.

Animals↗
PubMed1987

Estrogens and cell death in murine uterine luminal epithelium.

The luminal epithelium of adult ovariectomized mice responds to estradiol-17 beta with a synchronised wave of DNA synthesis and mitosis. Estriol, however, although producing a similar DNA-synthetic and mitotic response fails to cause an increase in cell number owing to a wave of cell death occurring at mitosis. In the present study it was shown that cells died by two different routes. The majority died by apoptosis but, unusually, a minority also died by necrosis. In the apoptotic cells the cytoplasm became dense, the endoplasmic reticulum and nuclear cisternae dilated; chromatin became marginated the nucleus shrank and became deeply infolded and contorted. Apoptosis, however, was uncharacteristic in that the nucleus failed to fragment, form caps or show disruption before the cells died by membrane rupture. Furthermore, the cells were frequently lost in sheets from the epithelium into the lumen. Part of the biochemical explanation for this onset of cell death comes from the accelerated loss from the tissue of estriol when compared to estradiol-17 beta. This resulted in a decline in protein and rRNA biosynthesis and a failure to complete ribosomal maturation. Evidence in favour of this explanation came from experiments that showed a return to the estradiol-17 beta level of response and an inhibition of cell death when the occupancy of the estriol receptor was maintained.

Animals↗
PubMed1981

The effect of oral estrogen therapy on serum FSH and LH levels in young women with hyper-gonadotrophic ovarian failure.

Fourteen women, 18--46 years old (median age: 28 years) with hypergonadotrophic ovarian failure were each treated daily for 21 days with 10 micrograms, 20 micrograms, 40 micrograms, and 60 micrograms ethinyl estradiol, 2,000 micrograms estriol, and 1,250 micrograms conjugated estrogens in six or more consecutive treatment cycles in a randomly assigned sequences. Before treatment and at the beginning of the 3rd week of each of the mentioned estrogen regimens, basal serum FSH and LH levels were measured. During the last 5 days of each treatment cycle, 10 mg of oral norethisterone acetate were given in addition to the estrogen, and after a treatment-free interval of 7 days the next estrogen regimen was begun according to the random list. FSH values were inversely related to the various dosages of ethinyl estradiol; the upper normal range with the exception of the periovulatory phase was reached with 40--60 micrograms ethinyl estradiol. FSH levels during treatment with 1250 micrograms of conjugated estrogens were similar to those found during treatment with 20 micrograms ethinyl estradiol. When 2,000 micrograms of estriol were given daily, FSH levels rose of pretreatment values. LH behaved similarly except that during treatment with 2,000 micrograms of estriol and 10 micrograms of ethinyl estradiol values above pretreatment levels were found.

Administration, Oral↗
PubMedDate not supplied

Urinary 17-ketosteroids in diabetic and non-diabetic pregnancies.

The excretion of estriol into the maternal urine is an effective means of evaluating the fetus in pregnancies complicated by a number of metabolic disorders, such as chronic hypertension, renal disease, pre-eclampsia, etc. It is generally used in the management of pregnancies complicated by maternal diabetes mellitus even though some question has been raised as to its validity for this disorder. In this study we have evaluated estriol precursors in the form of 17-ketosteroids in the urine of pregnant women with mild diabetes mellitus as well as a non-diabetic control group. Urinary total estrogen excretion was also determined. Diabetics were found to excrete significantly higher amounts of 17-ketosteroids than the non-diabetic group. The possible significance of this finding in relation to the dynamics of estriol production in pregnancy is discussed.

17-Ketosteroids↗
PubMedDate not supplied

Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17 beta-estradiol.

Naringenin, quercetin and kaempferol, which may be found in glycoside form in natural compounds such as grapefruit, are potent inhibitors of cytochrome P-450 metabolism. The influence of these flavonoids on the metabolism of 17 beta-estradiol was investigated in a microsome preparation from human liver. The flavonoids were added in concentrations of 10, 50, 100, 250 and 500 mumol/l to the microsome preparation. The metabolism of 17 beta-estradiol was concentration dependently inhibited by all the flavonoids tested. Addition of the flavonoids to the microsome preparation did not influence estrone formation, while a potent inhibition of estriol formation was observed. At the highest concentrations tested of the respective flavonoid, there was approximately 75-85% inhibition of estriol formation. However, naringenin was a less potent inhibitor of 17 beta-estradiol metabolism as compared to quercetin and kaempferol. The most likely mechanism of action of the flavonoids on 17 beta-estradiol metabolism is inhibition of the cytochrome P-450 IIIA4 enzyme, which catalyzes the reversible hydroxylation of 17 beta-estradiol into estrone and further into estriol. These hydroxylation processes represent the predominant steps of the hepatic metabolic conversion of endogenous as well as exogenous 17 beta-estradiol. This interaction would be expected to inhibit the first-pass metabolism of 17 beta-estradiol, and this has recently been demonstrated after oral administration of 17 beta-estradiol to women.

Adult↗
PubMedDate not supplied

Demonstration of estrogen receptors in the skin.

The occurence of high affinity and limited capacity estrogen receptors in skin specimens was investigated and the concentrations of cytoplasmic and nuclear receptors were studied in 14 normal and 22 castrated women. The skin estrogen receptor levels were low in all cases examined, although they usually exceeded the limit value used for estrogen receptor levels in breast cancer tissue. The cytoplasmic and nuclear receptor concentrations in normal women varied from 2.4 to 9.0 and from 1.5 to 7.0 fmol/mg cytosol protein, respectively. The receptor was present as a very high affinity binding component (KD = 0.2- 1.6 x 10(-9)M). The estrogen receptor concentrations in the skin during estriol succinate and estriol valerate therapy were at roughly the same level as during the normal menstrual cycle. The patients who received no replacement therapy after castration displayed the lowest skin estrogen receptor levels. The share of nuclear receptors seemed to be smaller on average during the normal menstrual cycle and in castrated patients not given estrogen therapy than in women treated with estriol succinate or estradiol valerate.

Adult↗
PubMed2006

A kinetic study on the lactoperoxidase catalyzed oxidation of estrogens.

Lactoperoxidase, which is produced in mammary glands, is proposed to be involved in carcinogenesis, because of its ability to react with estrogenic molecules, oxidizing them to free radicals. In the present study the reactivity towards six species (estradiol, ethynylestradiol, estriol, estrone, pregnenolone and mestranol) was investigated by means of a NADH-coupled system. The enzyme activity towards estradiol, ethynylestradiol, estriol and estrone did not vary much, suggesting that the different substituents in the D-ring of the steroid had little effect on the reaction. A somewhat higher K (m)-value was obtained with estriol; possibly because of a more effective splitting of the enzyme-substrate complex into products. Pregnenolone, without resonance in the A-ring, and a methyl group in 19-position, did not react with the enzyme, in spite of having the proposed essential hydroxyl group in 3-position. Mestranol, with a methoxy group in 3-position, did not react with the enzyme either, supporting the suggestion that lactoperoxidase reacts with the 3-hydroxyl group of the estrogens.

Animals↗
PubMed1976

Diagnosis of placental sulfatase deficiency..

Placental sulfatase deficiency has been found in four pregnancies (cases 1 to 4) with inappropriately low levels of urinary estriol excretion (less than 1.3 mg. per day near term gestation) associated with healthy neonates. The basis of the diagnosis in these cases was the greatly limited capacities for hydrolysis of 14C-dehydroepiandrosterone sulfate (DHA-S) and 3H-estrone sulfate (0.2 mugCi each) to the free steroids during incubation of placental homogenates. Placental aromatase activities in vitro for free DHA and the concentrations of appropriate estrogen precursors in cord blood were normal or elevated. The defect was diagnosed prenatally in two of these cases on the basis of failure to increase the maternal excretion of urinary estriol (0.6 to 0.7 and 1.3 to 1.3 mg. per day, respectively) following acute instillation of DHA-S (250 mg.) into the amniotic fluid and on normal levels of estrogen precursors in cord blood. In comparison, a twofold increase in maternal estriol excretion was observed after infusing DHA-S into the amniotic cavity of a "high-risk" pregnancy having normal sulfatase and aromatase activities in vitro (case 5). These enzyme activities were also found to be similarly normal in another placenta from an undergrown fetus (case 6) and in six normal placentas. The clinical features of these pregnancies, the first ones described from the western hemisphere, are similar to reported cases: the newborn progeny are healthy males who appear to be developing normally. The prenatal diagnosis of the sex-specific placental enzyme defect has been made possible by the use of an intra-amniotic DHA-S loading test.

Amniotic Fluid↗