Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ESTRADIOL”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources
PubMed1986

Experimental findings on the estrogenic activity of estradiol enantate.

In a first attempt to find out the estrogenic activity of the monthly injectable contraceptive composed of dihydroxyprogesterone acetophenide 150 mg + estradiol enantate 10 mg (Perlutal, Topasel), estradiol enantate (estra-1,3,5(10)-triene-3-ol-17 beta-heptanoat), estradiol benzoate and ethinylestradiol were compared in rats of the Chbb: THOM species. Estradiol benzoate potency was significantly higher than that of estradiol enantate: 20.34 (15.57-26.31) times in the vaginal cornification test in castrated females; 2.21 (1.63-2.98) times in the uterine weight test also in castrated rats and 2.91 (1.86-4.54) times in the vaginal opening test in immature rats. Ethinylestradiol, orally administered in the first two tests, was less active than the other two parenterally given substances; it overcame them in the vaginal opening test, when all substances were perivaginally administered. The duration of action of equivalent doses on the vaginal smear in castrated females resulted higher for estradiol enantate: 2.52 times more than estradiol benzoate and 5.2 times more than ethinylestradiol. Based on these results and on preexistent literature, the estradiol enantate dosis which would be sufficient to obtain the endometrial proliferation in women was extrapolated and compared with those already established of estradiol benzoate and ethinylestradiol. Finally, the possibility that the estrogenic potency of the injectable contraceptive treatment can be similar or lower than the oral one with pills containing ethinylestradiol 0.030-0.050 mg is discussed.

Animals↗
PubMed1983

Somatostatin enhances binding of [3H]estradiol to a cytosolic protein in rat pancreas. Possible role of oligopeptide coligands in secretion.

The cytosol fraction of rat pancrease can bind [3H] estradiol specifically and extensively. In contrast to the rat uterus, the binding protein in pancreas requires an accessory factor as a coligand in the steroid-binding reaction. Removal of this accessory factor by passage of the cytosol through CM Affi-Gel blue columns renders eluate fractions virtually incompetent with respect to binding of [3H]estradiol (10 nM). Certain synthetic oligopeptides such as N-benzoyl-L-argininyl-p-nitroanilide, as well as an endogenous accessory factor, can reactivate binding of [3H]estradiol. Thus, localization of the protein that binds [3H]estradiol following chromatography with CM Affi-Gel blue columns can be determined readily by assaying eluate fractions in the absence and presence of either accessory factor or N-benzoyl-L-argininyl-p-nitroanilide. Addition of somatostatin (tetradecapeptide referred to as SRIF14; somatotropin release inhibiting factor) to the activatable, but incompetent, eluate fractions, also enhanced binding of [3H]estradiol. The effect of SRIF14 was biphasic. The threshold concentration required for activation of [3H]estradiol binding was about 1 microM, and maximal stimulation occurred at 25 microM. At higher concentrations of SRIF14, binding declined and reached basal levels at about 75 microM. The concentrations of somatostatin required for activation of binding of [3H]estradiol in vivo may be lower than those indicated above since 1) preparations containing [3H]estradiol-binding protein also contained an SRIF14 peptidase. Following incubation of [125I-Tyr1]SRIF14 with these preparations there was loss of binding of radiolabeled peptide with SRIF14 antiserum. 2) The biphasic nature of SRIF14 activation may reflect feedback inhibition of [3H]estradiol binding by a degradation product of SRIF14. Since SRIF14 has been identified in the delta- (or D-) islet cells of the pancreas, and in concentrations that may be in the microM range, the possibility is raised that these cells serve a paracrine function with respect to acinar cell secretion.

Animals↗
PubMed1998

Estradiol protects mesencephalic dopaminergic neurons from oxidative stress-induced neuronal death.

Oxidative stress is important in the process of dopaminergic neuronal degeneration in Parkinson's disease. Recent studies suggest that estrogens have neuroprotective effects in neurodegenerative disorders, including Alzheimer's disease. In the present study, we investigated neuroprotection against oxidative stress afforded by estradiol using primary neuronal culture of the rat ventral mesencephalon. Oxidative stress induced by glutamate, superoxide anions, and hydrogen peroxide caused significant neuronal death. Although simultaneous administration of 17beta-estradiol and glutamate did not show any significant effects, preincubation with 17beta-estradiol provided significant neuroprotection against glutamate-induced neurotoxicity (ED50 was 50 microM for dopaminergic and 15 microM for nondopaminergic neurons). Neuroprotection occurred even after a brief preincubation with 17beta-estradiol and was not significantly blocked by either an estrogen receptor antagonist or a protein synthesis inhibitor. These findings indicate that the neuroprotection against glutamate neurotoxicity is mediated by neither estrogen receptors nor activation of genome transcription. Other steroids (corticosterone, testosterone, and cholesterol) did not provide significant neuroprotection against glutamate-induced neurotoxicity. Furthermore, preincubation with 17beta-estradiol provided neuroprotection against neuronal death induced by both superoxide anions and hydrogen peroxide. Dichlorofluorescin diacetate, a marker of oxygen radicals, revealed that preincubation with 17beta-estradiol suppressed intracellular oxygen radicals induced by hydrogen peroxide. The biologically inactive stereoisomer of estradiol, 17alpha-estradiol, provided neuroprotection against glutamate-induced toxicity in dopaminergic neurons, as well as the 17beta isoform. 17Alpha-estradiol may be a potential therapeutic agent used to prevent dopaminergic neuronal death induced by oxidative stress in Parkinson's disease.

Animals↗
PubMed1996

Characterization of a 7 day 17 beta-estradiol transdermal delivery system: pharmacokinetics in healthy postmenopausal women.

To assess the delivery characteristics of a new 7 day 17 beta-estradiol transdermal delivery system (TDS), estradiol and estrone pharmacokinetics were evaluated following a single 7 d application of one TDS or two TDSs in 24 healthy, postmenopausal women in a nonblind, randomized, two-period crossover study. Serial blood samples and total urine output were collected before (baseline measurement of endogenous hormone) and during TDS application, and for 24 h (urine) or 72 h (blood) following TDS removal. Serum was assayed for estradiol and estrone by a validated radioimmunoassay (RIA) method. The combined amounts of estradiol and its conjugates, and estrone and its conjugates in urine were determined by validated RIA methods. Overall, one or two estradiol TDSs were well tolerated by healthy, postmenopausal female volunteers. Estradiol absorption from the TDS was characterized by a zero-order process and was dose proportional, resulting in average steady-state serum estradiol concentrations of 16 and 33 pg mL-1 above baseline during the 7 d application of one and two TDSs, respectively. Parallel but smaller increases in serum estrone concentrations were observed, resulting in an increase in the serum estradiol/estrone concentration ratio from approximately 0.2 at baseline to median values of 0.64 and 0.88 during application of one and two TDSs, respectively. The 7 day 17 beta-estradiol TDS delivered a nominal estradiol dose of 0.02 mg/24 h during the intended wear period.

Administration, Cutaneous↗
PubMed1981

Control of the secretory cell cycle in cat oviduct by estradiol and progesterone.

The control of the secretory cell cycle by estradiol and progesterone in the oviduct of the cat was studied using light and electron microscopy. The epithelium in ovariectomized animals was cuboidal with no evidence of secretory activity. Estradiol treatment induced hypertrophy, hyperplasia, and the differentiation of both secretory and ciliated cells. Differentiation of the secretory cell included the development of an extensive area of basal rough endoplasmic reticulum and a large supranuclear Golgi region. Apical secretory granules were already present after 3 days of estradiol treatment, and after 4 to 5 days maximum hypertrophy and differentiation had occurred. Most cells contained several apical electron-dense granules; however, no large accumulation of granules in any one cell was ever observed. Occasional release of secretory product by exocytosis occurred during chronic treatment with estradiol. Rapid elevation of the serum levels of estradiol or progesterone by means of IV injection did not enhance exocytosis or result in any ultrastructural alterations. The chronic administration of progesterone to estradiol-primed animals resulted in rapid cell atrophy, dedifferentiation, and death (apoptosis) within the epithelium of the oviduct. Secretory granules were no longer observed after 2 days of estradiol and progesterone treatment, and after 7 days the epithelium was approximately the same height as that measured in ovariectomized animals. These data illustrate that estradiol induces the differentiation and maintains the mature state of the secretory cell within the oviductal epithelium of the cat, and that progesterone has an immediate antiestrogenic effect on these cells. This study also suggests that the secretory product is released gradually, as the granules form and mature during chronic estradiol administration.

Animals↗
PubMed1987

Mitotic inhibition and chromosome displacement induced by estradiol in Chinese hamster cells.

We tested diethylstilbestrol (DES) and 17 beta-estradiol as mitotic arrestants to determine their effects on chromosome distribution, spindle microtubules, and the cytoplasmic microtubule complex (CMTC) in the Chinese hamster strain Don. Cytological experiments assessed micronuclei induction, chromosome displacement, and anaphase recovery. Indirect immunofluorescence microscopy with antibody to tubulin and electron microscopy were used to illustrate effects on microtubules. Both DES and estradiol were potent inhibitors of mitosis when applied to cells in vitro. Estradiol induced micronuclei at a greater frequency than did DES. Estradiol-arrested metaphases often contained misaligned chromosomes despite the presence of a bipolar spindle and an equatorial plate. Equatorial plates were not observed in DES-arrested cells. Cells recovered quickly from estradiol exposure upon removal of the steroid. The frequency of abnormal metaphases and abnormal anaphases declined as the recovery period increased. Microtubule experiments showed that DES inhibited spindle assembly and disassembled the CMTC, whereas estradiol, at similar concentrations, arrested mitosis in a manner that allowed spindle assembly. A definite effect on the CMTC by estradiol could not be determined. However, changes in cell morphology were observed. In the presence of estradiol, centrosomes organized microtubules that joined with kinetochores of chromosomes at the equatorial plate as well as with those of misaligned chromosomes. Misaligned chromosomes appeared predominantly at polar regions of mitotic cells. Following drug removal, the pole-oriented chromosomes reoriented at the equatorial plate. The unique arresting properties of estradiol may prove useful in studies of chromosome migration and segregation during mitosis.

Anaphase↗
PubMed1993

Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat.

We have previously shown that the density of dendritic spines on hippocampal CA1 pyramidal cells is dependent on circulating estradiol and progesterone and fluctuates naturally during the 5 day estrous cycle in the adult rat. To date, however, no detailed characterization of the roles that these hormones play in regulation of spine density has been made. In order to determine the time courses and extent of the effects of estradiol and progesterone on dendritic spine density, we have analyzed the density of dendritic spines on the lateral branches of the apical dendritic tree of Golgi-impregnated CA1 hippocampal pyramidal cells in several experiments. In summary, our findings included the following: (1) Following ovariectomy, circulating estradiol is undetectable within 24 hours; however, spine density decreases gradually over a 6 day period. (2) Spine density does not decrease any further up to 40 days following ovariectomy. (3) Treatment with estradiol alone can reverse the ovariectomy-induced decrease in spine density. (4) Spine density begins to increase within 24 hours following estradiol benzoate injection in an ovariectomized animal, peaks at 2 and 3 days, then gradually decreases over the next 7 day period. (5) Although free estradiol is metabolized more rapidly than estradiol benzoate, there is no difference in the rate of decrease in spine density following injection of either form. (6) Progesterone has a biphasic effect on spine density in that progesterone treatment following estradiol initially increases spine density for a period of 2 to 6 hours but then results in a much sharper decrease than is observed following estradiol alone. By 18 hours following progesterone treatment, spine density is decreased nearly to 6 day ovariectomy values. (7) Treatment of intact rats with the progesterone receptor antagonist, RU 486, during the proestrus phase of the estrous cycle inhibits the proestrus to estrus drop in spine density. These findings account for both the gradual increase and rapid decrease in spine density which we have previously observed during the estrous cycle and indicate that progesterone in particular may be an important factor in the regulation of rapid morphologic changes which occur naturally in the adult brain.

Animals↗
PubMed1992

Genes involved in tumor invasion and metastasis are differentially modulated by estradiol and progestin in human breast-cancer cells.

Invasion of basement membranes by cancer cells is a critical step in metastasis, which requires the coordinated expression of specific genes such as laminin receptors and metalloproteinases. Estradiol and progesterone modulate the clinical progression of steroid-sensitive breast cancers; however, little is known about the molecular regulation of the invasive phenotype by these hormones. We therefore examined the effects of 10 nM estradiol and/or 10 nM progestin R5020 on the expression of 2 non-integrin laminin binding proteins, the 67-kDa laminin receptor (67LR) and HLBP31 as well as the 72-kDa type-IV collagenase (MMP-2) and its inhibitor, TIMP-2, in steroid-receptor-positive (T47D and MCF-7) and -negative (MDA-MB 231) human breast-cancer cells. The relative steady-state level of 67LR mRNA was increased 2- to 3-fold by estradiol in both MCF-7 (p < 0.001) and T47D (p < 0.001) cells, also by R5020, alone or in combination with estradiol, in T47D cells (p < 0.001) and to a much less extent in MCF-7 cells. HLBP31 mRNA and protein levels were increased 2- to 3-fold (p < 0.001) by R5020 alone or in combination with estradiol, but not by estradiol alone. None of the steroid treatments affected the expression or activity of MMP-2. Interestingly, however, TIMP-2 mRNA levels and protein expression in MCF-7 and T47D cells were 50% down-regulated (p < 0.001) by treatment with R5020 or R5020 plus estradiol, but not by treatment with estradiol alone. None of these genes were modulated in steroid-independent MDA-MB231 cells. The data suggest that estradiol and progesterone might act as coordinators regulating specific genes in the steroid-sensitive breast-cancer cell, leading to the acquisition of the metastatic phenotype.

Breast Neoplasms↗
PubMed1992

Effect of impurities on estradiol crystallization in a sustained-release implant.

During the development of a silicone rubber implant for the delivery of estradiol 17-beta some batches of implants made from a certain lot of commercial estradiol inexplicably developed surface crystals of estradiol after several days of storage. An impurity profile was obtained for 28 lots of estradiol by a newly developed HPLC method. One or more impurities may have had a role in the spontaneous crystal growth on the surface of the implants, because the one lot of estradiol that initially had surface crystals on aging produced acceptable implants after multiple recrystallizations. Attempts to isolate suspected impurities for characterization were unsuccessful. During the manufacture of the implants, temperatures sufficient to melt the estradiol (mp, 173-179 degrees C) were used. It was expected that, upon implant cooling, melted impure estradiol would form a thermodynamically more active (i.e., noncrystalline) physical form. This metastable form could have migrated to the implant surface, where ambient conditions favored crystallization. Because melted estradiol of a higher purity tended to crystallize more readily, it was less likely to form a glass upon cooling. The phenomenon of surface crystallization was limited to one lot of estradiol with the highest level of impurities. Data from differential scanning calorimetry studies supported this conclusion.

Calorimetry, Differential Scanning↗
PubMed2000

Estradiol regulation of follistatin and inhibin alpha- and beta(B)-subunit mRNA in avian granulosa cells.

Estradiol modulation of granulosa cell growth and regulation of follistatin and inhibin alpha- and beta(B)-subunit mRNA were investigated in cultured chicken granulosa cells. Granulosa cells were isolated and pooled according to size from the F(4) + F(5), small yellow (SYF), and large white (LWF) follicles. Isolated and dispersed granulosa cells were then cultured in the absence or presence of 1 x 10(-5) M 17 beta-estradiol. In Experiment 1 (n = 4 replications) the effect of estradiol on the growth of granulosa cells from the different-sized follicles was examined at 24 and 48 h of culture. Untreated and treated granulosa cells from all three follicle sizes proliferated during culture, and cell viability for all cultures was over 95% throughout the experiment. After 48 h the untreated cultures for all follicle types had 1.6 to 2.2 times (P < 0.05) more cells than the estradiol-treated cultures. In Experiment 2 (n = 3 replications), the cultures were terminated at 4 and 24 h after plating. Follistatin mRNA levels were higher in estradiol-treated cells at 24 h in F(4) + F(5) follicles, at 4 and 24 h in the SYF, and at 4 h in the LWF. beta(B)-subunit mRNA levels were also increased by estradiol at 4 h in F(4) + F(5) cells and at 4 and 24 h in the LWF. Steady state mRNA levels for the alpha-subunit were higher (P < 0.05) in estradiol-treated cultures at 4 and 24 h in F(4) + F(5) follicles and at 24 h in the SYF. Immunoreactive alpha-subunit protein, however, was not increased by estradiol treatment. Thus, whereas estradiol inhibited granulosa cell growth, it exerted a generally stimulatory effect on the expression of FS and the inhibin alpha- and beta(B)-subunit mRNA.

Animals↗
PubMed1996

Protection from myocardial reperfusion injury by acute administration of 17 beta-estradiol.

Although several studies have demonstrated that chronic exposure to estrogen appears to be cardioprotective, acute circulatory effects of estrogen are largely unknown. Therefore, we studied the effects of acute administration of 17 beta-estradiol in myocardial ischemia/reperfusion. Cats were subjected to 90 min of left anterior descending coronary artery (LAD) occlusion and 270 min of reperfusion (MI/R). Either the estrogenic steroid, 17 beta-estradiol or its non-estrogenic isomer, 17 alpha-estradiol was administered (i.v.) 30 min prior to reperfusion at 1 microgram/kg bolus followed by a constant infusion lasting the remaining duration of the protocol at 1 microgram/kg/h. Control cats were subjected to sham MI/R. Cats treated with 17 beta-estradiol demonstrated a marked reduction in cardiac necrosis following MI/R compared to cats receiving 17 alpha-estradiol or phosphate buffered saline (17 +/- 2% v 33 +/- 1% or 34 +/- 4% area of necrosis indexed to the area-at-risk, P < 0.01). In addition, cats receiving 17 beta-estradiol exhibited reduced myocardial PMN infiltration in necrotic tissue as compared to 17 alpha-estradiol treated cats. Moreover, 17 beta-estradiol administration attenuated neutrophil adherence to ex vivo coronary vascular endothelium compared to the two controls (44 +/- 8 PMNs/mm2 v 79 +/- 7 PMNs/mm2 or 86 +/- 7 PMNs/mm2 P < 0.01). These data indicate that 17 beta-estradiol protects against myocardial ischemia/reperfusion, in part, by attenuating PMN infiltration and subsequent injury due to PMN mediator release.

Animals↗
PubMed1997

Effects of 17beta-estradiol on action potentials and ionic currents in male rat ventricular myocytes.

This study describes electrophysiological effects of estrogens in isolated male rat ventricular myocytes. According to the literature these cells do not express the nuclear estrogen receptor. Action potentials or membrane currents were recorded in the whole-cell configuration with standard techniques. Action potential durations (APD) measured at a level of 0 mV (APD 0) and -70 mV (APD -70) were prolonged by 17beta-estradiol (0.5 Hz stimulation frequency, 24-26 degrees C). Threshold concentration was 1 micromol/l. At the highest concentration used (30 micromol/l) no saturation of the response was reached and APD 0 was 162% and APD -70 was 230% of the respective control. The resting potential remained unaffected in most cells. The prolongation induced by 17beta-estradiol developed fast and reached a steady state 10 min after start of hormone superfusion. Effects of estrogen were completely reversible during 10-15 min wash-out with hormone-free solution. The extent of prolongation (10 micromol/l 17beta-estradiol) was frequency dependent. Expressed as percentage of the respective control APD 0 (or APD -70) was 115% (188%) at 0.05 Hz, 118% (163%) at 0.5 Hz and 99% (129%) at 5 Hz stimulation frequency. The response was stereoselective, because 30 micromol/l 17alpha-estradiol did not prolong action potentials (APD 0: 101%, APD -70: 104% of the respective control, 0.5 Hz stimulation frequency). The endogenous estrogens estrone and estriol were less effective than 17beta-estradiol. With 30 micromol/l estrone (0.5 Hz stimulation frequency) APD 0 was 103% and ADP-70 148% of control and with 30 micromol/l estriol APD 0 was 135% and APD -70 137% of control. The prolongation of action potentials can be explained by inhibition of transient outward current which, in rat ventricle, is composed of fast (i[to,f]) and slowly (i[to,s]) inactivating components. At 30 micromol/l 17beta-estradiol i(to,f) was reduced to 50% and i(to,s) to 43% of their maximal amplitudes. The voltage sensor of i(to,f) or i(to,s) was hardly affected. Additionally, 17beta-estradiol decreased the calcium current (i[Ca,L]) to 76% (10 micromol/l) and 38% at 30 micromol/l. The inwardly rectifying potassium current (i[K1]) was reduced partly with 30 micromol/l 17beta-estradiol and its amplitude was 72% of control at -90 mV (inward current flow) and 65% at -40 mV (outward current flow). These results show that 17beta-estradiol is active in cardiac cells which do not express the nuclear estrogen receptor. The hormone exerts class III activity and reduces calcium inward current. These effects, however, occur in vitro with concentrations above the physiological level and therefore may be without significance in vivo.

Action Potentials↗
PubMed2004

The relative effect of endogenous estradiol and androgens on menopausal bone loss: a longitudinal study.

OBJECTIVE: The aim of this study was to assess the relative strength of the association of endogenous estradiol and androgens with bone loss at the lumbar spine and femoral neck during the menopausal transition. DESIGN: A longitudinal study of a population-based cohort of 159 Australian-born women who at baseline had a mean age of 50.0 years (SD=2.4) and had menstruated in the prior 3 months. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck on up to three occasions. RESULTS: Of the 159 participants, 50 had two BMD measurements and 109 had a third measure. The mean time between the first and final measures for the whole group was 39 months and at the time of the final measures 49% of the participants had become postmenopausal. The mean percentage change/year in lumbar spine BMD was -0.9% (95% CI, -1.1 to -0.6) and at the femoral neck, -0.5% (95% CI, -0.7 to -0.2). A highly significant association with estradiol at the final time point was found, whereas the contribution of estradiol at baseline was negligible. The variance explained by estradiol levels was 19% and 11% for change in BMD at the LS and FN, respectively. Excluding baseline estradiol values and using the average of change in BMD at the LS and FN, the final regression equation estimated that an estradiol level of 330 pmol/l (95% CI, 274 to 386) and 245 pmol/l (95% CI, 194 to 296) is required for preservation of LS and FN BMD, respectively. A stepwise linear regression model was used to assess the effect of age, BMI, estradiol, testosterone, DHEAS, SHBG, and free testosterone index on changes in BMD and found that only the final estradiol level had a significant association with change in BMD. CONCLUSION: Endogenous estradiol was the only hormone among those investigated to have a significant effect on bone mineral density during the menopausal transition.

Bone Density↗
PubMed2004

Prediction of incident osteoporotic fractures in elderly women using the free estradiol index.

A decline in postmenopausal estrogen concentration accelerates postmenopausal bone loss. We have examined the predictive power of endogenous estrogen production, DXA hip bone density (BMD), and heel quantitative ultrasound (QUS) on incident clinical fracture in a prospective 3-year population based, randomised controlled trial of calcium supplementation. Baseline blood testing on 1499 women mean (SD) age 75 (3) years for estradiol and sex hormone binding globulin measurements and ankle QUS measurements (Lunar Achilles) was undertaken. Bone density was measured using DXA (Hologic 4500A) at 1 year. Incident clinical fractures were confirmed by X-ray. At 3 years, 10% had sustained more than one incident fracture. The fracture group had significantly lower levels of free estradiol index (FEI) (0.40+/-0.44 versus 0.49+/-0.54 pmol/nmol), hip BMD (0.776+/-0.129 versus 0.815+/-0.124 g/cm(2)) and measures of QUS (BUA 98+/-8 versus 101+/-8 db/Hz, SOS 1504+/-22 versus 1514 +/-26 m/s; stiffness 67+/-11 versus 71+/-11 % mean young adult), respectively, than the non-fracture group. After adjustment for age, weight, use of topical estrogen, calcium supplementation and prevalent fracture, incident fracture was predicted by free estradiol index (HR per SD: 1.43:95%CI: 1.08-1.91, P=0.013). After adjustment for BMD, SOS or stiffness, the free estradiol index no longer predicted fracture. When examined separately, the presence of a vertebral or an appendicular fracture was associated with an 18% lower free estradiol index compared with no fracture. The risk of vertebral fracture increased with decreased free estradiol index (HR per SD reduction: 1.63:95% CI: 0.91-2.92); the risk of appendicular fracture also increased with decreased free estradiol index (HR per SD reduction: 1.45:95% CI: 1.05-2.01) after adjustment for age, weight, use of topical estrogen, calcium supplementation and prevalent fracture. After further adjustment for hip BMD or QUS measures, the effect of free estradiol index was no longer significant for vertebral or appendicular fractures. Therefore, a low free estradiol index increases the probability of having an incident fracture as a result of decreased BMD. These data confirm the importance of postmenopausal estrogen concentration in the pathogenesis of osteoporosis in elderly women.

Administration, Topical↗
PubMed1999

Role of estradiol in puerperal psychosis.

RATIONALE: Postpartum period has been considered a time of increased risk for the development of psychiatric disorders with long-lasting adverse consequences. Psychoses are the most severe of these illnesses and can be resistant to psychiatric medication. OBJECTIVE: We present two women with puerperal psychosis who had low serum estradiol, were refractory to neuroleptic medication but responded successfully to estradiol treatment. METHODS: Serum estradiol concentration was measured at baseline and during the treatment with sublingual 17-beta estradiol. Treatment effect was evaluated using Brief Psychiatric Rating Scale. RESULTS: Both patients had a low pretreatment estradiol concentration (28 and 54 pmol/l). During treatment with estradiol, the rise in serum estradiol coincided with a decline of psychotic symptoms. Discontinuation of estradiol treatment resulted in a rebound of florid psychotic symptoms in both cases. CONCLUSIONS: Estradiol may have a causal relation to postpartum psychosis and significance in the treatment of this illness.

Administration, Sublingual↗
PubMed2003

Effect of 17beta-estradiol on immunosuppression induced by ultraviolet B irradiation.

BACKGROUND: The risk of skin cancer is lower in females than in males, and photoimmunosuppression caused by ultraviolet (UV) radiation is thought to be involved in the progression of skin cancer. OBJECTIVES. To determine the effect of 17beta-estradiol on immunosuppression and contact hypersensitivity (CHS) caused by ultraviolet B (UVB) irradiation. METHODS: Systemic immunosuppression was induced in C57BL mice that had been sensitized with 0.5% fluorescein isothiocyanate (FITC) through the skin by a single exposure to UVB (10 kJ/m2). The CHS response was assessed after applying FITC to mice treated intraperitoneally with 17beta-estradiol, tamoxifen (17beta-estradiol antagonist), or antiestradiol antibody. Levels of serum interleukin-10 (IL-10) were measured in treated mice and control mice using an enzyme-linked immunosorbent assay (ELISA). To assess the effect of 17beta-estradiol on keratinocytes, Pam-212 cells were exposed in vitro to UVB radiation and treated for 24 h with 17beta-estradiol. The IL-10 content of the supernatant was measured using an ELISA. RESULTS: The CHS response in UVB-irradiated mice was significantly suppressed in comparison to that in nonirradiated mice. Consecutive intraperitoneal injections of 17beta-estradiol significantly reduced UVB-induced suppression of the CHS response in male mice, whereas injection of tamoxifen or antiestradiol antibody significantly promoted UVB-induced suppression in female mice. Treatment with 17beta-estradiol decreased the serum IL-10 levels in CHS-suppressed male mice after UVB irradiation, but treatment with tamoxifen or antiestradiol antibody increased the serum IL-10 levels in female mice. Treatment with 17beta-estradiol reduced IL-10 production by UVB-irradiated Pam-212 cells in a dose-dependent manner. CONCLUSIONS: These results suggest that 17beta-estradiol prevents UVB-induced suppression of the CHS response caused by immunosuppressive cytokines produced by keratinocytes.

Animals↗
PubMed2005

Estradiol protects cultured articular chondrocytes from oxygen-radical-induced damage.

Osteoarthritis (OA) is aggravated in menopausal women possibly because of changed serum estrogen levels. Estradiol has been postulated to affect oxidative stress induced by reactive oxygen species (ROS) in articular chondrocytes. We generated ROS in cultured bovine articular chondrocytes by incubating them with combined Fe2SO4, vitamin C, and hydrogen peroxide. The release of thiobarbituric-acid-reactive substances (TBARS, lipid peroxidation) and lactate dehydrogenase (LDH, membrane damage) was measured photometrically. Various estradiol doses and vitamin E, serving as control with an established anti-oxidative capacity, were applied either upon each exchange of medium and during radical production (strategy 1) or only during radical production (strategy 2). In chondrocytes incubated according to strategy 1, the production of TBARS and LDH release were significantly suppressed by 10(-10)-10(-4) M estradiol or by vitamin E. Under strategy 2, the production of TBARS was significantly suppressed at estradiol concentrations higher than 10(-6) M, whereas LDH release was inhibited at concentrations of 10(-6)-10(-4) M. Vitamin E showed no significant effects. As repeated application of estradiol and vitamin E produced the best results, estradiol, like vitamin E, was speculated to accumulate in the plasma membrane and to decrease membrane fluidity resulting in protection against lipid peroxidation (non-genomic effect). Thus, in contrast to the neuroprotective effect of 17beta-estradiol in supraphysiological doses reported recently, the anti-oxidative potential of estradiol appears to protect articular chondrocytes from ROS-induced damage when the hormone is given repeatedly in a physiological range. Decreased estradiol levels may therefore contribute to menopausal OA in the long term.

Animals↗
PubMed1985

Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors.

In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction.

Animals↗