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PubMed1982

Relationship of luteinizing hormone, pregnanediol-3-glucuronide, and estriol-16-glucuronide in urine of infertile women with endometriosis.

The concentration of luteinizing hormone (LH), pregnanediol-3-glucuronide (PGD), and estriol-16-Glucuronide (E3G) were measured in daily morning urine specimens from 53 infertile women. In 26 of 29 women with various degrees of proven endometriosis, two distinct midcycle peaks of LH were found 2 or 3 days apart. Patients with LH peaks separated by 3 days had significantly more severe endometriosis than those with a single peak. Maximum concentrations of E3G were found to be delayed until after the first LH peak in these patients, and PGD concentrations did not rise until the time of the second LH peak, making actual luteal function of shorter duration than normal. From the data on LH, it appears that an inappropriate hormonal feedback mechanism is operative in endometriosis.

Adult↗

PubMed1983

Plasma estradiol is superior to ultrasound and urinary estriol glucuronide as a predictor of ovarian hyperstimulation during induction of ovulation with menotropins.

In order to compare the effectiveness of 8:00 A.M. plasma 17 beta-estradiol (E2), 24-hour urinary estriol glucuronide (E3G), and ultrasound as predictors of ovarian hyperstimulation, 70 cycles of induction of ovulation with 5:00 P.M. to 8:00 P.M. injection of menotropins from 28 subjects were evaluated. Hyperstimulation was four times more frequent in pregnancy than in nonpregnancy cycles (P less than 0.005). The hyperstimulation score (range, 0 to 6) was correlated with plasma E2 (0.63, P less than 0.01), the number of follicles (0.31, P less than 0.05), the duration of treatment (0.31, P less than 0.05), and urinary E3G (0.25, P less than 0.05). Plasma E2 was the best predictor of the hyperstimulation score, and plasma E2 was far superior to both urinary E3G and the number of follicles. Management with ultrasound alone is insufficient to prevent severe ovarian hyperstimulation. With this protocol, human chorionic gonadotropin may be given as soon as the first follicle reaches 1.4 cm in diameter as long as plasma E2 is less than 4000 pg/ml. The values of plasma E2 are dependent on the interval between blood sampling and injection of menotropins.

Estradiol↗

PubMed2002

Estriol retards and stabilizes atherosclerosis through an NO-mediated system.

Estriol (E3) has little effect on the female genitals. E3 is used in hormone replacement therapy, particularly in Europe and Japan, since it obviates the need for progestin administration. However, the effect of E3 on atherosclerosis has not been elucidated. In this study, we evaluated the effect of E3 on the progression of atherosclerosis in a rabbit model. Thirty-six rabbits total were used. Twenty-eight were bilaterally oophorectomized, and 8 were not. The rabbits were divided into 5 groups and treated for 12 weeks as follows. Gp I (n = 8) was fed a high cholesterol diet (HCD; standard diet plus 0.5% cholesterol); Gp II (n = 8) was fed a HCD with E3 (0.3 mg/kg/day); Gp III (n = 8) was fed a HCD with 17beta estradiol (E2) (0.1 mg/kg/day); Gp IV (n = 8), the non oophorectomized group, was fed a HCD; and Gp NC was oophorectomized (n = 4), and fed a regular diet. E3 treatment increased the plasma E2 and E3 levels in Gp II. The plasma lipid levels were not altered by the E2 or E3 treatment. A HCD diminished the acetylcholine-induced NO mediated relaxation in the thoracic aorta. The E2 treatment (Gp III) and E3 treatment (Gp II) restored the aortic basal NO release and the aortic cyclic GMP levels, particularly effectively in the E3 group. E3 treatment also decreased the atherosclerotic area, and its effect was comparable with E2 (surface involvement: 41.2 +/- 5.1% in Gp I; 10.1 +/- 2.7% in Gp II; and 6.5 +/- 1.3% in Gp III). All four hyperlipidemic groups showed an increase of eNOS mRNA in the aortae, and this was especially pronounced in Gps II and III. The level of peroxynitrite, as determined by immunohistochemical nitrotyrosine staining, was lower in Gps II and III than in Gp I. E3 strongly activates NO-mediated systems, and could play a role in retarding the progression of atherosclerosis and in stabilizing atheroma.

Acetylcholine↗

PubMed2000

Serial salivary estriol to detect an increased risk of preterm birth.

OBJECTIVE: To evaluate serial measurements of salivary estriol (E3) to detect increased risk of spontaneous preterm labor and preterm birth. METHODS: A masked, prospective, multicenter trial of 956 women with singleton pregnancies was completed at eight United States medical centers. Saliva was collected weekly, beginning at the 22nd week of gestation until birth, and tested for unconjugated E3 by enzyme-linked immunosorbent assay. Women were separated into high-risk and low-risk groups using the Creasy scoring system. RESULTS: A single, positive (at or above 2.1 ng/mL) salivary E3 test predicted an increased risk of spontaneous preterm labor and delivery in the total population (relative risk [RR] 4.0, P <.005), in the low-risk population (RR 4.0, P < or =.05), and in the high-risk population (RR 3.4, P =.05). Two consecutive positive tests significantly increased the RR in all study groups, with a dramatic improvement in test specificity and positive predictive value but only a modest decrease in sensitivity. In women who presented with symptomatic preterm labor, salivary E3 identified 61% of those who delivered within 2 weeks, using a threshold of 1.4 ng/mL. CONCLUSION: Elevated salivary E3 is associated with increased risk of preterm birth in asymptomatic women and symptomatic women who present for evaluation of preterm labor.

Adult↗

PubMed2003

Maternal serum unconjugated estriol as a predictor for Smith-Lemli-Opitz syndrome and other fetal conditions.

OBJECTIVE: To assess the clinical value of low maternal serum unconjugated estriol (E3) level for diagnosing Smith-Lemli-Opitz syndrome and other fetal clinical conditions in pregnant members of a large health maintenance organization. METHODS: We studied serum unconjugated E3 levels in 120,071 gravidas having California Expanded Alpha-Fetoprotein prenatal screening at 15-20 weeks' gestation during a 5-year period. RESULTS: Of the 120,071 women, 323 (0.27%) had low unconjugated E3 levels (less than or equal to 0.2 ng/mL, or 0.15 multiples of the median). Excluding women who were screened too early or who had indeterminate screening results, 103 (0.08%) women with unexplained low unconjugated E3 level remained; of these 103 women, 33 had negative screening results and 68 had positive screening results, and two were tested too late for interpretation. Intrauterine fetal death occurred in 39 (57%) of the 68 women with low unconjugated E3 and positive screening results and occurred in two (6%) of the 33 women with low unconjugated E3 levels and negative screening results, a significant difference (P <.001). Two cases of Smith-Lemli-Opitz syndrome were identified and the patients did not survive the neonatal period; one was a therapeutic abortion for severe oligohydramnios, and the other died at age 48 hours. Low unconjugated E3 level also predicted presence of steroid sulfatase deficiency, a much more common X-linked skin disorder characterized by ichthyosis. CONCLUSION: Low maternal serum unconjugated E3 diagnosed more cases of steroid sulfatase deficiency and undetected intrauterine fetal death than Smith-Lemli-Opitz syndrome (1:60,000 prevalence), although the clinical importance of having this information prenatally is uncertain.

Adult↗

PubMed1997

Second-trimester maternal serum CA-125 versus estriol in the multiple-marker screening test for Down syndrome.

OBJECTIVE: To determine the ability of second-trimester maternal serum CA-125 levels to detect fetal Down syndrome. METHODS: From stored, second-trimester maternal serum analyzed previously with the multiple-marker screening test for fetal Down syndrome, we selected 306 samples from euploid pregnancies and 22 samples from Down syndrome pregnancies at 14-20 weeks' gestation. CA-125 levels were measured by enzyme-linked immunosorbent assay and converted to gestational week-specific multiples of the median (MoM). RESULTS: The mean maternal age (+/- standard deviation) of the study population was 35.5 +/- 5.3 years. The Down syndrome group CA-125 mean MoM was significantly higher than the euploid group mean MoM (1.47 +/- 0.51 MoM versus 1.05 +/- 0.44 MoM; P < .001). CA-125 at or above 1.5 MoM identified 10 of 22 (45%) Down syndrome cases. Substituting CA-125 for estriol (E3) in the multiple-marker screening test resulted in a lower screen-positive rate (67 of 328, 20% [95% confidence interval {CI} 16, 25] versus 91 of 328, 28% [95% CI 23, 33]) with a similar Down syndrome detection rate (18 of 22, 82%). Alternatively, when the screen-positive rate was held constant, the Down syndrome detection rate improved (20 of 22, 91% [95% CI 71, 99] versus 18 of 22, 82% [95% CI 60, 95]). CONCLUSIONS: Down syndrome pregnancies have higher second-trimester maternal serum CA-125 levels than euploid pregnancies. CA-125 may be superior to E3 in the multiple-marker screening test for fetal Down syndrome.

Adult↗

PubMed1997

Race-ethnicity-specific variation in multiple-marker biochemical screening: alpha-fetoprotein, hCG, and estriol.

OBJECTIVE: To identify any race-ethnicity-specific differences in serum alpha-fetoprotein (AFP), hCG, and unconjugated estriol (E3) levels in women between 14 and 21 weeks' gestation. METHODS: Data from the 3-year period 1992-1994 were analyzed from 208,257 women who had AFP screening, of whom 155,142 also had hCG and 62,121 also had E3 screened, between 14 and 21 weeks' gestation. Subjects were categorized into four groups: white, black, Asian, and Hispanic. RESULTS: There was a consistent pattern of analyte differences across gestational ages. Levels for AFP were generally higher in Asian and black women than in Hispanic and white women (median AFP at 16 weeks-31.2, 30.9, 27.4, 27.3, respectively), and levels of hCG and E3 were highest in Asians (hCG at 16 weeks-34.7, 30.3, 28.2, 26.8, respectively). Weight correction for AFP, hCG, and E3 levels did not compensate for the ethnic differences. CONCLUSIONS: Because hCG and E3 demonstrate the same general pattern of differences as AFP among ethnic groups, averaging values for all ethnic groups tends inappropriately to lower calculated Down syndrome risks for black and Asian women. Additionally, the slopes of the curves are not parallel, such that separate data bases are preferable to multiplicative correction factors. Separate data bases should be used in laboratories with volume sufficient to permit the establishment of race-ethnicity-specific regressions. Use of separate data bases should result in more accurate screening.

Chorionic Gonadotropin↗

PubMed1998

Association of low unconjugated estriol in the second trimester and adverse pregnancy outcome.

OBJECTIVE: To investigate the association between a low unconjugated estriol (uE3) in the second trimester and adverse pregnancy outcomes. METHODS: Three hundred nine women who underwent second-trimester maternal serum alpha-fetoprotein (AFP)-hCG-uE3 screening were divided into two groups: those with uE3 at most 0.75 multiples of the median (MoM) (n = 81) and those with uE3 exceeding 0.75 MoM (n = 228). Entry criteria included: hCG below 2 MoM, AFP below 2 MoM, age less than 35 years at delivery, complete prenatal records, and completed delivery. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for a variety of adverse pregnancy outcomes. RESULTS: After adjusting for smoking and hCG, women with uE3 at or below 0.75 MoM were found to have significantly higher odds of developing fetal growth restriction, low amniotic fluid index (AFI), and small for gestational age (SGA) with ORs (and 95% CIs) of 6.73 (2.55, 17.74), 3.85 (1.53, 9.68), and 2.89 (1.27, 6.57), respectively, for each of the outcomes. CONCLUSION: Low uE3 in the second trimester appears to be associated with fetal growth restriction, low AFI, and SGA, and the risk seems to be independent of risk for adverse infant outcome associated with elevated AFP or hCG.

Adult↗

PubMed1999

Urine free beta-hCG and total estriol for Down syndrome screening during the second trimester in an Asian population.

OBJECTIVE: To evaluate second-trimester free beta-hCG and total estriol (E3) in the maternal urine as markers for Down syndrome screening in an Asian population. METHODS: Free beta-hCG and total E3 were measured in the urine samples of 28 Taiwanese Down syndrome pregnancies and 268 unaffected singleton pregnancies at 14-25 weeks. Results were normalized to urine creatinine concentrations and converted to multiples of the median (MoM) levels. Gestational ages were estimated by ultrasound measurements. RESULTS: Median values of free beta-hCG, total E3, free beta-hCG to total E3 ratio, and the free beta-hCG to total E3 MoM ratio in Down syndrome pregnancies were 4.75 MoM, 0.66 MoM, 8.99 MoM, and 9.51, respectively. At a 5% false-positive rate, the observed detection rates were 36% (ten of 28) with total E3, 71% (20 of 28) with free beta-hCG, 68% (19 of 28) with free beta-hCG/total E3, and 71% (20 of 28) with free beta-hCG/total E3 MoM. When combined with maternal age, the expected detection rates were 65% with total E3, 71% with free beta-hCG, 76% with free beta-hCG/total E3, 80% with free beta-hCG/total E3 MoM, and 89% when combining free beta-hCG, total E3, and maternal age. CONCLUSION: Urine free beta-hCG and total E3 are useful markers for Down syndrome screening during the second trimester in Taiwanese women.

Adult↗

PubMed2002

Estradiol enhances and estriol inhibits the expression of CYP1A1 induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in a mouse ovarian cancer cell line.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous pollutant and promoter of carcinogenesis. This study investigated the interaction between TCDD and different estrogens in a cancer cell line (ID8) derived from mouse ovarian epithelium. TCDD-induced ethoxyresorufin-O-deethylase (EROD) activity and cytochrome P4501A1 (CYP1A1) expression in a dose- and time-dependent manner. Estrogen receptor (ER) alpha mRNAs were constitutively expressed, but ER beta and progesterone receptor (PR) mRNAs were not expressed. Induction of EROD by TCDD was completely inhibited by a alpha-naphthoflavone and phenanthroline, two aryl hydrocarbon receptor (AhR) antagonists. Progesterone and gonadotropins (FSH and LH) had no effect on the induction of EROD by TCDD. Congeners of 17beta-estradiol (E2) increased the induction of EROD activity by TCDD dose-dependently in the relative potency order: estrone (El)>E2> or = 4-hydroxyestradiol (4OHE2)> or = 2-hydroxyestradiol (2OHE2). In contrast, estriol (E3) decreased EROD activity induced by TCDD. E2 increased TCDD-induced CYP1A1 protein and mRNA whereas E3 decreased both the protein and mRNA. E2 did not alter luciferase activity induced by TCDD in cells transfected with a luciferase reporter containing dioxin response elements (DRE) or a CYP1A1 promoter. In contrast, E3 dose-dependently decreased the luciferase activity. A pure anti-estrogen (ICI 182780) inhibited the interaction between E2 and TCDD but did not block E3's effect on EROD activity. These results indicate that E2 may affect TCDD-induced CYP1A1 expression by a mechanism different from E3 in ID8 cells. It appears that the potentiation of E2 in the induction of CYP1A1 by TCDD occurs by a mechanism involving ER alpha since a specific ER antagonist blocked the potentiation. The inhibitory effect of E3 may be due to a rapid direct effect on EROD and a later suppression of CYP1A1 expression.

Animals↗

PubMed1997

Comparison of the long-term effects of oral estriol with the effects of conjugated estrogen, 1-alpha-hydroxyvitamin D3 and calcium lactate on vertebral bone loss in early menopausal women.

We investigated the long-term effects of oral estriol (E3) on bone mineral density (BMD) at the lumbar spine and biochemical indices of bone turnover in early menopausal women. We studied 64 healthy early menopausal women who were treated for 24 months with 2.0 mg E3 plus 2.5 mg medroxyprogesterone acetate daily (E3 group, n = 15), 0.625 mg of conjugated estrogen plus 2.5 mg medroxyprogesterone acetate daily (CE group, n = 19), 1.0 microgram 1-alpha-hydroxyvitamin D3 daily (D3 group, n = 13), or 1.8 g calcium lactate containing 250 mg of elemental calcium daily (Ca group, n = 17). The BMD at the third lumbar vertebra was determined by quantitative computed tomography, and serum levels of osteocalcin (OC) and total alkaline phosphatase (Alp), as well as urinary ratios of calcium-to-creatinine (Ca/Cr) and hydroxyproline-to-creatine (Hyp/Cr), were evaluated at baseline and every 6 months. After 24 months of treatment, the BMD decreased significantly by 12 +/- 4.5% (mean +/- S.E.) in the D3 group and 14 +/- 2.5% in the Ca group, but not in the E3 group (-4.1 +/- 4.8% from baseline) and in the CE group (-0.9 +/- 3.2% from baseline). The serum levels of Alp and OC decreased or remained unchanged in the E3 and CE groups, but increased in the D3 and Ca groups. The urinary Ca/Cr was decreased in the E3 and CE groups, but not in the D3 and Ca groups. The urinary Hyp/Cr decreased in the CE group, was unchanged in the E3 and D3 groups, and increased in the Ca group. Uterine bleeding occurred less frequently in the E3 than in the CE group (2.4 +/- 4.2 versus 13.1 +/- 14.8 days/person per year, P < 0.001). The bone-preserving effect of 2.0 mg of oral E3 was comparable to that of 0.625 mg of conjugated estrogen and was superior to that of 1.0 microgram 1-alpha-hydroxyvitamin D3 and 1.8 g Ca. Our findings suggest that a reduction in bone turnover in the E3 group may have contributed to the preservation of bone.

Administration, Oral↗

PubMed1999

Simultaneous determination of alpha-fetoprotein, human chorionic gonadotropin and estriol in serum of pregnant women by time-resolved fluoroimmunoassay.

We have developed a simple and rapid time-resolved fluoroimmunoassay (TR-FIA) for simultaneous determination of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and estriol (E3) using europium and samarium ion chelate. In the proposed method, we used a combination of a 96-well microtiter plate for the AFP and hCG assay and transferable solid phase plate for the E3 assay. Therefore, these analytes could be measured simultaneously. The measurable ranges for AFP, hCG and E3 by the proposed method were 3.91-1000 ng ml(-1), 877-250000 IU l(-1) and 0.39 100 ng ml(-1), respectively. The proposed method which utilized characteristics of a rare earth ion chelate, was convenient (unnecessary diluting samples), quick (96 assays for 2 h), and required only a small quantity sample (50 microl). The principle of this proposed method is applicable to other antigens.

Antibody Specificity↗

PubMedDate not supplied

Atheroprotective effect of estriol and estrone sulfate on human vascular smooth muscle cells.

In patients with atherosclerosis, fibrosclerotic focuses are induced by multiplication of vascular smooth muscle cells (VSMC), and they are regulated by cytokines and regulators. There have been few reports about the atheroprotective effect of estriol (E(3)). Estrone sulfate (E(1)-S) is the predominant estrogen of conjugated equiline estrogens, which is commonly used in hormone replacement therapy, but it should be hydrolyzed by steroid sulfatase (STS) to enter the cells of target tissues. The purpose of this study was to detect STS in VSMC and to investigate whether E(3) and E(1)-S have atheroprotective effects like E(2). First, we detected the presence of STS mRNA in VSMC by in situ hybridization. We then examined the changes in the expression of mRNAs of cytokines, namely, PDGF-A chain, IL-1, IL-6 and TGF-beta, in VSMC, in the presence and absence of E(3) and estrogens. As a result, the expression of PDGF-A chain, IL-1 and IL-6 mRNAs was suppressed by E(3) (P<0.05 vs control) significantly like E(1)-S and E(2), but that of TGF-beta mRNA was not significantly affected by any estrogen. These results indicate that E(1)-S can be hydrolyzed by STS in VSMC, and that E(3) may regulate the cytokines by suppressing the production of mRNAs. It is suggested that there is a possibility of E(1)-S and E(3) having a direct effect on vessels in atherogenesis.

Arteriosclerosis↗

PubMed2001

Synthesis of ring B unsaturated estriols. Confirming the structure of a diagnostic analyte for Smith-Lemli-Opitz syndrome.

[structure: see text] Brief partial syntheses are described for ring B unsaturated estriols, which are candidate metabolites diagnostic for Smith-Lemli-Opitz syndrome prenatally. These steroids are also likely metabolites of the Premarin preparation used in estrogen replacement therapy. Equilin (8) was converted in three steps to 7-dehydroestriol, which was isomerized to 8-dehydroestriol. The simplicity of the transformations belies the lability of these previously inaccessible metabolites and their synthetic precursors.

Biomarkers↗

PubMed2003

Pregnancy estriol, estradiol, progesterone and prolactin in relation to birth weight and other birth size variables (United States).

OBJECTIVE: Because birth weight has been positively associated with adult life breast cancer risk and pregnancy estrogens have been hypothesized to affect breast cancer risk in the offspring, we have evaluated the association of pregnancy estriol (E3), estradiol (E2), progesterone and prolactin in maternal serum samples collected during the 16th and 27th gestational week with birth size parameters. METHODS: Prospective study of 230 Caucasian women who delivered a live singleton after 37-42 weeks of gestation. RESULTS: E3 at the 27th gestational week was significantly positively associated with birth weight, birth length and placental weight. Progesterone at the 27th gestational week was also significantly positively associated with birth weight and placental weight but, after mutual adjustment among the studied pregnancy hormones, these associations weakened considerably. There was also inconsistent evidence that SHBG and prolactin at the 27th gestational week may be respectively positively and inversely related with birth size parameters. Measurements during the 16th gestational week were generally unrelated to birth size parameters. CONCLUSIONS: Because E3 is a dominant estrogen during pregnancy, the positive association of it with birth weight allows the use of the latter as a proxy of in utero exposure to estrogens in breast cancer investigations.

Adolescent↗

PubMed1988

Serum unconjugated estriols in insulin-dependent diabetic pregnancies: normative data and clinical relevance.

The purpose of this study was to establish normative reference values for serum unconjugated estriol (E3) concentrations in insulin-dependent diabetic pregnancy. There were 1973 samples analyzed in 63 diabetic pregnancies not complicated by fetal distress and/or neonatal asphyxia. These samples were compared with 867 samples collected in 25 pregnancies complicated by fetal distress and/or neonatal asphyxia and 103 samples collected in seven nondiabetic, uncomplicated pregnancies. E3 values were found to be significantly higher in diabetic compared with nondiabetic healthy gravid women, correlating with infant birthweight. The percent change of daily E3 values from the highest previous 3 days mean (maximum mean) was 1 +/- 27% (mean +/- SD). The 95% confidence limit for this percent change indicates that a decrease of 52% or more is theoretically seen in 2.5% of the observations. Using the traditional decrease of 40% currently used in the literature, there were false-negative and false-positive predictions of fetal distress and/or neonatal asphyxia at rates unacceptable for patient management. The use of E3 determinations in combination with nonstress test-contraction stress test did not improve the predictability of this latter test. Serum E3 determinations are of little clinical value in the management of insulin-dependent diabetic pregnant women.

Asphyxia Neonatorum↗

PubMed2003

Effects of estriol on cell viability and 1,25-dihydroxyvitamin D3 receptor mRNA expression in cultured human osteoblast-like cells.

It is clinically evident that administration of estriol (E3) increases the bone mass density of the lumbar vertebrae in postmenopausal women, and that combined treatment with estrogen and 1,25-dihydroxyvitamin D3 (VD3) increases femoral neck bone mass density compared with treatment with estrogen alone in postmenopausal osteoporotic women. However, the molecular mechanism whereby treatment with E3 affects osteoblast cell function is still unknown. This study was conducted first to examine the comparative effects of E3 and VD3 on the cell viability of cultured human osteoblast-like cells (HOS) and second to determine whether E3 affects VD3 receptor mRNA expression in HOS. The cell viability and VD3 receptor mRNA expression of cultured HOS were assessed by MTT assay and semi-quantitative reverse transcriptase-polymerase chain reaction with Southern blot analysis, respectively. The treatment with E3 increased the cell viability of cultured HOS compared with untreated control cultures. The increase in cell viability caused by the treatment with E3 was further augmented by the combined treatment with VD3. The addition of either E3 (3.52 x 10(-8) mol/l) or E3 (3.52 x 10(-7) mol/l) to cultured HOS for 24 h resulted in a fourfold and eightfold increase, respectively, in VD3 receptor mRNA expression in HOS, compared with that in untreated control cultures. These results suggest that E3 may up-regulate the cell viability of osteoblast cells, and that the concomitant treatment with E3 and VD3 further augments the cell viability being associated with an E3-induced increase in VD3 receptor mRNA expression in those cells.

Calcitriol↗

PubMed2005

Effects of estriol on proliferative activity and expression of insulin-like growth factor-I (IGF-I) and IGF-I receptor mRNA in cultured human osteoblast-like osteosarcoma cells.

The present study was undertaken to elucidate whether estriol (E3) affects the proliferative activity and the expression of insulin-like growth factor-I (IGF-I) mRNA and IGF-I receptor (IGF-IR) mRNA in cultured human osteoblast-like osteosarcoma cells (HOS TE85). In this study, the effects of E3 on cultured HOS TE85 cells were compared with those of 17 beta-estradiol (E2). HOS TE85 cells were subcultured in phenol red-free Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum for 72 h and then stepped down to serum-free conditions for an additional 72 h in the absence or presence of E3 (3.52 x 10(-9), 3.52 x 10(-8), 3.52 x 10(-7) mol/l) or E2 (3.67 x 10(-8) mol/l). Treatment with either E3 (3.52 x 10(-8), 3.52 x 10(-7) mol/l) or E2 (3.67 x 10(-8) mol/l) resulted in an increase in the number of cultured HOS TE85 cells and their uptake of bromodeoxyuridine. Northern blot hybridization with a IGF-I cDNA probe revealed that RNA prepared from cultured HOS TE85 cells contained IGF-I mRNA transcripts of 1.8, 4.4 and 7.5 kb. Treatment with either E3 (3.52 x 10(-9), 3.52 x 10(-8), 3.52 x 10(-7) mol/l) or E2 (3.67 x 10(-8) mol/l) resulted in increased expression of the three mRNA transcripts relative tot hose in untreated control cultures. Semi-quantitative, reverse transcription polymerase chain reaction analysis showed that the 440-bp IGF-IR mRNA transcript was present in HOS TE85 cells and that treatment with either E3 or E2 did not affect the IGF-IRmRNA expression in these cells. These results demonstrate that E3 (3.52 x 10(-9), 3.52 x 10(-8), 3.52 x 10(-7) mol/l) exerts profound effects on the proliferative potential of cultured HOS TE85 cells, compatible with that of E2 (3.67 x 10(-8) mol/l), through the induction of IGF-I mRNA expression without affecting IGF-IR mRNA expression in these cells.

Bromodeoxyuridine↗