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PubMed2000

Role of 17beta-estradiol and/or progesterone on insulin sensitivity in the rat: implications during pregnancy.

The mechanism for the development of insulin resistance in normal pregnancy is complex and is associated with serum levels of both progesterone and 17beta-estradiol. However, it remains unclear whether estrogens alone or progestins alone can cause insulin resistance, or whether it is a combination of both which produces this effect. We attempted to determine the role played by progesterone and/or 17beta-estradiol on the phenomena of sensitivity to insulin action that take place during pregnancy in the rat. Ovariectomized rats were treated with different doses of progesterone and/or 17beta-estradiol in order to simulate the plasma levels in normal pregnant rats. A euglycemic/hyperinsulinemic clamp was used to measure insulin sensitivity. At days 6 and 11, vehicle (V)- and progesterone (P)-treated groups were more insulin resistant than 17beta-estradiol (E)- and 17beta-estradiol+progesterone (EP)-treated groups. Nevertheless, at day 16, the V, EP and E groups were more resistant to insulin action than the P group. On the other hand, the V, EP and E groups were more insulin resistant at day 16 than at day 6, whereas the P group was more insulin resistant at day 6 than at day 16. Our results seem to suggest that the absence of female steroid hormones gives rise to a decreased insulin sensitivity. The rise in insulin sensitivity during early pregnancy, when the plasma concentrations of 17beta-estradiol and progesterone are low, could be due to 17beta-estradiol. However, during late pregnancy when the plasma concentrations of 17beta-estradiol and progesterone are high, the role of 17beta-estradiol could be to antagonize the effect of progesterone, diminishing insulin sensitivity.

Analysis of Variance↗

PubMed2004

Effects of peroxisome proliferator activated receptors-alpha and -gamma agonists on estradiol-induced proliferation and hyperplasia formation in the mouse uterus.

It is suggested that the action of peroxisome proliferator-activated receptors (PPARs) cross-talks with estrogen signaling in the uterus. However, it is not known how PPAR agonists affect estrogen-dependent processes in the uterus, especially proliferation and morphogenetic changes. The effects of agonists of PPAR-alpha and -gamma on proliferative and morphogenetic reactions in the uterus under short- and long-term estrogen treatments were therefore examined. Ovariectomized mice were treated with estradiol dipropionate (4 micro g/100 g, s.c., once a week) or vehicle and rosiglitazone (PPAR-gamma agonist) or fenofibrate (PPAR-alpha agonist) or with no additional treatment for 2 days or for 30 days. Treatment with estradiol and PPAR agonists for 2 days did not affect uterine mass. In mice treated with estradiol and rosiglitazone for 2 days, proliferation was enhanced and levels of estrogen receptors-alpha and beta-catenin were decreased in all uterine tissues. Treatment with estradiol and fenofibrate for 2 days had the opposite effects on the parameters tested. In animals treated with estradiol and rosiglitazone for 30 days, uterine mass was increased, abnormal uterine glands and atypical endometrial hyperplasia were found more often and levels of estrogen receptors-alpha and beta-catenin were decreased. In animals treated with estradiol and fenofibrate for 30 days, uterine mass was decreased, most of the uterine glands had a normal structure, no cases of atypical hyperplasia were diagnosed, proliferative activity was declined and the levels of estrogen receptors-alpha and beta-catenin were markedly higher. Treatment with rosiglitazone or fenofibrate did not affect the serum estradiol level in the mice which received estradiol together with PPAR agonists for 30 days. Thus, rosiglitazone exerted the proliferative and morphogenetic effects of estradiol, but fenofibrate had the opposite effect. The actions of rosiglitazone and fenofibrate are associated with changes in the expression of estrogen receptors-alpha and beta-catenin in the uterus.

Animals↗

PubMed1987

Determination by ultrafiltration of the fraction of unbound estradiol and its variation in peritoneal fluid during the menstrual cycle.

An ultrafiltration method employing a Centrifree filter for determining the unbound fraction of estradiol was studied. Centrifugation was performed under conditions similar to those in vivo. Good correlation was recognized between this method and the equilibrium dialysis. This method was employed to determine the unbound fraction of estradiol in the serum and the peritoneal fluid of 26 infertility patients classified according to their menstrual dates. The total estradiol and progesterone contents in the peritoneal fluid were high after ovulation. There was no significant difference in the percentage of unbound estradiol in the serum among various groups. In the peritoneal fluid, however, the percentage of unbound estradiol for the day 12-14 patients was 4.5 +/- 0.2% in contrast with 3.8 +/- 0.4% for the day 15-18 group (p less than 0.05) and 3.5 +/- 0.1% (p less than 0.05) for the day 19-28 group. Moreover, the fraction (4.5%) of unbound estradiol in the peritoneal fluid of a patient with luteinized unruptured follicle (LUF) syndrome was comparable with that of patients in the follicular phase. The difference between the percentage of unbound estradiol in the peritoneal fluid before and after ovulation is considered to be due to the transudation of follicular estradiol in the follicular phase and the exudation of estradiol from the corpus luteum into the peritoneal cavity in the luteal phase.

Ascitic Fluid↗

PubMed1990

Transdermal estradiol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of menopausal complaints.

The estradiol transdermal therapeutic system is a cutaneous delivery device which delivers estradiol into the systemic circulation via the stratum corneum at a constant rate for up to 4 days. Physiological levels of estradiol (the major estrogen secreted by the ovaries in premenopausal women) can therefore be maintained in postmenopausal women with low daily doses because first-pass hepatic metabolism is avoided. In short term clinical studies, the beneficial effects of transdermal estradiol on plasma gonadotrophins, maturation of the vaginal epithelium, metabolic parameters of bone resorption and menopausal symptoms (hot flushes, sleep disturbance, genitourinary discomfort and mood alteration) appear to be comparable to those of oral and subcutaneous estrogens, while the undesirable effects of oral estrogens on hepatic metabolism are avoided. As with oral or injectable estrogen replacement therapy, concomitant sequential progestagen is recommended for patients with an intact uterus during transdermal estradiol administration, in order to reduce endometrial stimulation. Transdermal estradiol has been well tolerated in clinical trials, with local irritation at the site of application being the most common adverse effect. The incidence of systemic estrogenic effects appears to be comparable to that observed with oral therapy. Thus, transdermal estradiol offers near-physiological estrogen replacement in postmenopausal women in a convenient low-dose form which may avoid some of the complications of higher dose oral therapy. Long term epidemiological studies are warranted to determine whether transdermal estradiol therapy provides protection against osteoporosis and fractures and cardiovascular disease equivalent to that offered by oral and injectable estrogens. However, despite the importance of such data, it seems reasonable to conclude at this stage of its development that transdermal estradiol represents an important advance in hormone replacement therapy.

Administration, Cutaneous↗

PubMed2001

Effects of 17beta-estradiol on tension responses and fatigue in the skeletal twitch muscle fibers of frog.

The effects of 17beta-estradiol (10(-5) M), an active estrogen, on the tension and fatigue responses of single fiber or fiber bundle prepared from frog skeletal muscle were investigated. The administration of 17beta-estradiol caused a transient potentiation of tetanus tension by field stimulation at every minute. This potentiation was not affected by the presence of nicardipine, suggesting that the action of 17beta-estradiol would place the excitation-contraction (E-C) coupling beyond T-tubule depolarization. Fatigue was produced by repeated tetanic stimulation every second until tension declined to approximately 40% of the initial level. Fibers were then allowed to recover by having tetani given to them every minute. In the normal Ringer solution, the time to 50% of the initial tetanus tension was 41.7 s. With the presence of 17beta-estradiol, the time to 50% tension was faster than that of control. The presence of 17alpha-estradiol, a stereoisomer, caused no potentiation of tetanic tension to be stimulated every minute, and the rate of decline of fatigued response was almost the same as that of control, suggesting the existence of specific estrogen receptors in the frog muscle. In fatigued muscle with or without estrogen, the tension to field stimulation was transient and not sustained. When the fatigued muscle was again treated with field stimulation at every minute after the more-frequent stimulation, the recovery rate was increased in 17beta-estradiol. A prompt reduction in temperature to 5 degree C, from 20 degree C, in the presence of caffeine elicited the tension response, a rapid cooling contracture (RCC). The presence of 17beta-estradiol inhibited peak tension and maximum rate of rise of the RCC only after the repetitive electrical stimuli. These results suggest that the potentiation of contraction upon the electrical stimulation by 17beta-estradiol was induced by the increase of myoplasmic-free Ca(2+) concentration via an activation of some E-C coupling process. The 17beta-estradiol-induced facilitation of fatigue response to repetitive tetanus stimuli with high frequency may be due to an increase in the imbalance of Ca(2+) turnover in the cytoplasm.

Animals↗

PubMed1981

Estriol- and estradiol-17 beta-induced luteinizing hormone release in ovariectomized cows and ewes.

Two studies were conducted with ovariectomized animals to compare luteinizing hormone (LH) responses during the 24-hr period following an IM injection of either estriol or estradiol-17 beta. In Exp. 1, six long-term ovariectomized (6 months) beef cows were randomly assigned to be given 1 mg of estriol or estradiol 17 beta injected in 4 ml of corn oil. Two months later, the experiment was replicated in a switch back design. In Exp. 2, eight ewes that had been ovariectomized for 1 to 4 months were randomly assigned to be given 150 micrograms of estriol or estradiol-17 beta injected in 1.5 ml of corn oil. The initial increase in serum LH concentrations occurred earlier in both cows (P less than .01) and ewes (P less than .05) in response to estriol (8 to 9 hr) than in response to estradiol 17 beta (12 to 18 hr). In addition, duration of the decrease in LH release that occurred 1 hr after estrogen injection in ewes was 3 hr shorter (P less than .05) in response to estriol than in response to estradiol-17 beta. The total area under the LH response curve was greater for both cows (P less than .05) and ewes (P less than .01) given estradiol-17 beta than for those given estriol. Administration of estradiol-17 beta induced a 10-fold increase in serum estradiol-17 beta concentrations and a two to fourfold increase in serum estrone concentrations. Both estrogens returned to basal concentrations by 24 hr after administration. Peak serum estriol exceeded 300 pg/ml within 1 hr of estriol injection, but decreased to nondetectable levels within 12 hours. We concluded that estriol can stimulate LH release from the pituitary. Furthermore, the differential LH response to the two estrogens suggests that the positive effects of estriol are mediated earlier but that estradiol-17 beta is a more potent stimulus when administered as a single IM injection.

Animals↗

PubMed1986

Intrauterine migration of the porcine embryo: coordination of bead migration with estradiol.

Forty crossbred gilts were used in three experiments to examine the effects of estradiol on embryo migration. Small, spherical beads of Silastic glue containing either cholesterol or estradiol-17 beta were used to mimic embryo migration. In the first experiment, 10 cholesterol- and 10 estradiol-impregnated beads were injected into the tip of the uterine horns, either on the same side (n = 5) or opposite from each other (n = 5). The second experiment consisted of a localized release of cholesterol or estradiol and observing migration of cholesterol-containing beads inserted 10 cm anterior and posterior to this site (n = 5). In the third experiment, 10 cholesterol-impregnated beads were injected into either the tip or base of one uterine horn. Additionally, these gilts were exposed to vehicle or exogenous estradiol in a 2 X 2 factorial arrangement of treatments (n = 5). Results of these experiments indicated that cholesterol-impregnated beads migrated further (P less than .05) when adjacent to estradiol-containing beads than when in an opposite uterine horn. Localized release of estradiol failed to induce movement of beads away from the site of steroid release. Finally, beads inserted at the base of the uterus moved anteriorly following treatment of gilts with estradiol. We suggest from these experiments that the porcine uterine horn cannot discriminate between estradiol- and cholesterol-releasing beads and, further, lacks a coordinated ability to displace adjacent beads. A site-dose dependent mechanism(s) of estrogenic induction of migration may exist such that porcine embryos become bilaterally intermixed following posterior, then anterior, waves of uterine contractions.

Animals↗

PubMed1988

Follicular growth and estradiol influence on luteal function in mares.

Follicular growth, circulating estradiol concentrations and endometrial prostaglandin F2 alpha (PGF2 alpha) production were measured to determine whether there is an interrelationship among these factors associated with luteolysis. Follicular growth was monitored by rectal palpation every other day during diestrus in 16 mares. Plasma estradiol was determined for daily samples during all estrous cycles. Endometrial tissue was removed for PGF2 alpha analysis by radioimmunoassay on d 10, 12, 14 or 16 during several normal cycles and after d 30 during spontaneously prolonged cycles. Circulating estradiol concentrations were highly correlated with follicular diameter. Follicular growth was initiated before d 14 in normal cycles, thus estradiol was significantly elevated during the portion of diestrus prior to luteolysis. This was not the case during spontaneously prolonged cycles in which a) there was no correlation between follicular size and circulating estradiol, b) follicular growth was initiated an average of 19 d postovulation, and c) estradiol concentrations did not increase. Diestrous estradiol concentrations, during normal cycles, were significantly elevated immediately (72 to 24 h) prior to the time at which peak endometrial PGF2 alpha production occurred (d 12 and 14). During spontaneously prolonged cycles, estradiol concentrations did not rise at the time of expected luteolysis, and endometrial PGF2 alpha production was minimal in d 30 biopsies. Results suggest that diestrus follicular growth and its consequent estradiol production may play a role in initiating luteolysis through endometrial PGF2 alpha production and that delay or failure of this process may result in spontaneously prolonged corpora luteal function.

Animals↗

PubMed2000

Early follicular phase serum FSH as a function of age: the roles of inhibin B, inhibin A and estradiol.

OBJECTIVE: Reproductive aging in regularly cycling normal women is characterized by a gradual decline in ovarian follicle number and a progressive increase in serum follicle stimulating hormone (FSH), particularly over the age of 40 years. The lack of any consistent decrease in circulating estradiol and progesterone has led to the hypothesis that the FSH increase results from decreasing ovarian inhibin production. The aim of this study was to investigate the relationship between serum inhibins A and B, FSH and estradiol in normal women between the ages of 20 and 50 years. DESIGN AND PATIENTS: Serum from 66 regularly cycling subjects, aged 20-50 years, was collected on days 3-5 of the menstrual cycle for this cross-sectional study. MEASUREMENTS: Serum inhibin A and inhibin B levels were measured by specific enzyme-linked immunosorbent assays (ELISAs). Alpha subunit forms were determined by an immunofluorometric assay which detects all known monomeric and dimeric forms of inhibin A and inhibin B and free alpha subunit. FSH and estradiol levels were measured by immunoassay. Data were log transformed before analysis. RESULTS: Serum FSH, inhibin A and estradiol, but not inhibin B, were positively correlated (p < 0.05-p < 0.001) with age between years 20 and 50. Between 40 and 50 years, serum FSH was negatively correlated with inhibin B (r = -0.61, p < 0.001) and alpha subunit forms (r = -0.47, p < 0.05) and with estradiol (r = -0.39, p < 0.05), but not with inhibin A (r = -0.21, not significant). When log(FSH) was modelled as a function of log(inhibin B) and log(estradiol) with age fitted as a covariate, inhibin B only was a significant independent predictor of FSH (beta = -0.30, p < 0.01). Using purified inhibin A and B standards for the three assays, which were calibrated in terms of their alpha subunit content, serum inhibin A levels were 10-15% of those of inhibin B, with inhibin A + B levels being 22% of total alpha subunit levels. No significant correlation was observed between total inhibin alpha subunit and its dimers. The free alpha subunit, as determined from the difference in levels of total alpha subunit and inhibin A + B, remained relatively unchanged with age, suggesting that it is not differentially regulated. CONCLUSIONS: This study shows that, during the early follicular phase, FSH, inhibin A and estradiol but not inhibin B increase with age. Some of the increase in inhibin A and estradiol may be the result of accelerated follicular development with increasing age. Serum inhibin B and estradiol but not inhibin A are inversely correlated with FSH between ages 40 and 50, but only inhibin B is a significant independent predictor of FSH. This supports the postulate that inhibin B is the main form of inhibin regulating FSH at this stage of the menstrual cycle. During the early follicular phase, serum levels of inhibin A are presumably too low to play a significant physiological role or are less active.

Adult↗

PubMed2003

Endogenous estradiol metabolites stimulate the in vitro proliferation of human osteoblastic cells.

OBJECTIVES: Evidence is accumulating that estradiol metabolites are not merely waste products but may play physiologic and pathophysiologic roles. In the present study, effect of estradiol metabolites on the proliferation of human female osteoblasts was investigated for the first time and compared to effect of their parent substance 17beta-estradiol. MATERIALS AND METHODS: Osteoblasts from female hipbone were incubated with estradiol and estradiol metabolites at dosages of 10(-9), 10(-7) and 10(-5) M for 7 days. Cell proliferation was measured using a cell counter. RESULTS: Estradiol had no effect on cell proliferation at the tested concentrations. In contrast, the A-ring metabolites 2-hydroxyestrone, 2-hydroxyestradiol, 2-hydroxyestriol, 4-hydroxyestrone and 4-hydroxyestradiol displayed significant increases in cell proliferation, although only at high physiologic or pharmacologic dosages. Methylation ofthese metabolites completely abolished their proliferating property. For the D-ring metabolites estrone, estriol, estetrol and 16alpha-hydroxyestrone, no significant changes in cell proliferation were observed. CONCLUSION: The present results suggest that endogenous estradiol metabolites are capable of stimulating the proliferation of human female osteoblastic cells. None of the estradiol metabolites examined inhibited cell proliferation. Thus, estradiol metabolism may play a decisive role in development and maintenance of bone mass.

Cell Division↗

PubMedDate not supplied

[Oxidative destruction of estradiol after treatment with hydrogen peroxide catalyzed by horseradish peroxidase and methemoglobin].

It is shown that estradiol in the presence of horse radish peroxidase interacts with hydrogen peroxide, which is evidenced by an increase in its optical density at 280 nm. The photometering of samples containing estradiol and horse radish peroxidase upon their titration with hydrogen peroxide indicated that the increase in optical density stops after introducing hydrogen peroxide equimolar in concentration to estradiol. The stoichiometric ratio of estradiol consumed during oxidative destruction to hydrogen peroxide was 1:1. In the presence of ascorbate, the oxidative destruction of estradiol by the action of hydrogen peroxide, catalyzed by horse radish peroxidase, was observed only after a latent period and showed the same regularities as in the absence of ascorbate. It was found by calorimetry that, during the latent period, estradiol catalyzes the degradation of hydrogen peroxide and ascorbate without undergoing oxidative destruction. The substrates of the peroxidase reaction benzidine, 1-naphthol, and phenol interact with hydrogen peroxide in the presence of ascorbate and horse radish peroxidase in a similar way. Presumably, upon interaction with hydrogen peroxide in the presence of horse radish peroxidase, estradiol, like other substrates of this reaction, undergoes oxidative destruction by the mechanism of peroxidase reaction. It is shown that oxidative destruction of estradiol by the action of hydrogen peroxide can also be catalyzed by methemoglobin by the same mechanism. These data are important for understanding the role of estradiol in the organism and the pathways of its metabolic conversions.

Catalysis↗

PubMedDate not supplied

Do heavier women benefit from a higher dose of leuprolide acetate for suppression of serum estradiol?

OBJECTIVE: To determine if heavier women benefit from a higher dose of the gonadotropin-releasing hormone analogue leuprolide acetate (LA) depot in terms of suppression of serum estradiol. METHODS: This was a retrospective analysis of the effect of LA depot 3.75 mg and 7.5 mg on serum estradiol from a multicenter, double-blind, parallel-group, 12-week study of women with anemia due to bleeding from uterine leiomyomata. Serum estradiol levels were obtained at baseline and at week 12. Patients were divided into weight quartiles according to their baseline weight in kilograms: 46-<64, 64-<72, 72-<89, 89-159 (pounds-102-<140, 140-<159, 159-<196, 196-350). RESULTS: At baseline there was no statistically significant difference in estradiol level between groups as a whole or within weight quartiles. Within each group there was no relationship between weight and baseline estradiol. At week 12, whereas estradiol levels were significantly greater in the heavier patients in each of the groups (LA 3.75 mg, p = 0.044; LA 7.5 mg, p = 0.002), there was no significant difference in estradiol between groups as a whole or within any of the weight quartiles. Moreover, at week 12 there was no significant difference between groups in the percentage of patients with estradiol suppressed to the menopausal range. CONCLUSION: Heavier women do not benefit from a higher dose of LA depot (7.5 vs. 3.75 mg) for suppression of serum levels of estradiol.

Anemia↗

PubMedDate not supplied

Effects of PC-SPES on proliferation and expression of AR/PSA in androgen-responsive LNCaP cells are independent of estradiol.

Previous studies have suggested that the clinical efficacy of PC-SPES, a dietary supplement used frequently by men diagnosed with androgen-dependent (AD) or androgen-independent (AI) prostate cancer (CaP), is mechanistically attributed to estrogenic components present in the herbal mixture. To test this hypothesis, we compared estradiol (1 nM), potentially an active principle in PC-SPES, with PC-SPES (using an amount equivalent to 1 nM estradiol) on cell proliferation, induction of apoptosis, and regulation of prostate specific genes, PSA and AR, in androgen-responsive LNCaP cells. Cells cultured in steroid-proficient (FBS) or-deficient (CS-FBS) media to simulate hormonal status pre- and post-castration in vivo, were incubated with estradiol or PC-SPES. Proliferation was reduced in PC-SPES treated cells cultured in media supplemented with FBS or CS-FBS; in contrast, addition of estradiol had no effect on proliferation in FBS cultures, and elicited a 45% growth increase in CS-PBS-supplemented cultures. The differential proliferative response of LNCaP cells to PC-SPES vs. estradiol was also supported by changes in PCNA expression, cell viability, cell cycle phase distribution, and induction of apoptosis. Estradiol elicited time-dependent increases in secreted PSA, whereas PC-SPES suppressed PSA secretion, in both culture conditions. In FBS cultures, PC-SPES lowered intracellular AR and PSA by 61% and 17%, respectively, while estradiol increased intracellular PSA, in parallel with a 42% decrease in AR expression. In comparison with cells maintained with CS-FBS, estradiol induced substantial increases in both intracellular PSA and AR, whereas PC-SPES resulted in a smaller increase in intracellular PSA without affecting the expression of AR. These studies show that the antiproliferative and gene modulatory effects of PC-SPES in androgen-dependent human prostate cancer cells are mechanistically and functionally distinct from effects attributable to estradiol.

Antineoplastic Agents, Phytogenic↗

PubMed2003

Role of phosphatase PTEN in the activation of extracellular signal-regulated kinases induced by estradiol in endometrial carcinoma cells.

OBJECTIVES: To study extracellular signal-regulated kinase (ERK) activation in the endometrial carcinoma cell line Ishikawa with stimulation by 17-beta-estradiol, and to elucidate the role of phosphatase and tensin homologue (PTEN) and estrogen receptor (ER) subtype on the activation of ERKs. METHODS: Western blot was used to examine the expression of PTEN and PTEN (G129E) in Ishikawa cells after stable transfection as well as ERK activation in Ishikawa-EGFP, Ishikawa- PTEN and Ishikawa- PTEN (G129E) stimulated with various doses of 17-beta-estradiol for different lengths of time. Western blot was also used for examining the expression of ERalpha and ERbeta in NIH3T3 fibroblasts after transient transfection of pCXN2hERalpha and pCXN2hERbeta. Then, ERK activation was examined after stimulation with 17-beta-estradiol. RESULTS: 17-beta-estradiol activated ERK cascades (mainly ERK2) in Ishikawa cells. The activation of ERK increased gradually as concentration of 17-beta-estradiol also increased. The maximal activation of ERK2 took place 5 min after stimulation with 17-beta-estradiol. The activation of ERK2 was inhibited markedly by PTEN, but not by PTEN (G129E). 17-beta-estradiol activated ERK cascades in NIH3T3 fibroblasts after transient transfection of pCXN2hERalpha. CONCLUSIONS: 17-beta-estradiol activate ERK cascades in Ishikawa cells by integrating with ERalpha. Lipid phosphatase PTEN has an inhibitory role on the activation of ERK stimulated by 17-beta-estradiol in Ishikawa cells.

3T3 Cells↗

PubMed1992

The effect of administration of estradiol and testosterone on body growth of young male rats.

The influence of estradiol and testosterone on body growth of young male Wistar rats was investigated. In the first experiment, estradiol was given to intact ad libitum fed male rats at 32, 37 and 42 days of age. Moreover, two untreated groups of animals were used: one was fed restrictedly according to the food intake of animals receiving estradiol and another was fed ad libitum. The animals were sacrificed at 47 days of age. Both untreated groups of animals achieved significantly higher body weight and length of tibia than estradiol treated animals. Also the growth of the tail of untreated animals was more intensive than that of estradiol treated animals. In the second experiment, estradiol was given to intact ad libitum fed male rats at 30, 35 and 45 days of age. Moreover, testosterone was given to a half of these animals at 45, 50 and 55 days of age. The animals were sacrificed at 60 days of age. Administration of testosterone significantly increased the growth of the tail and tibia in comparison to the animals which did not receive testosterone after estradiol administration. The results of the present study show that the inhibitory effect of estradiol on body growth of young male rats is not only the result of decreased food intake and that testosterone can improve the skeletal growth of male rats altered by previously given estradiol.

Age Factors↗

PubMed1992

Effects of tamoxifen adjuvant therapy and a low-fat diet on serum binding proteins and estradiol bioavailability in postmenopausal breast cancer patients.

Serum was collected at intervals from postmenopausal breast cancer patients to determine the effects of tamoxifen adjuvant therapy and a low-fat dietary intervention, alone and in combination, on sex hormone-binding globulin (SHBG) concentrations and circulating estradiol bioavailability. Serum corticosteroid-binding globulin and follicle-stimulating hormone were also assayed as indicators of patient compliance to tamoxifen therapy. The immunoreactive SHBG concentration was higher (P less than 0.001) in 22 patients who had been treated with tamoxifen for 6-36 weeks when first sampled, compared with 27 who were not receiving tamoxifen therapy. Tamoxifen also produced a reduction in the percentage non-protein-bound estradiol (P less than 0.001) and percentage albumin-bound estradiol (P less than 0.01), the two biologically available fractions, and a corresponding increase in the percentage SHBG-bound estradiol (P less than 0.01). A longitudinal study of 7 patients showed significant reductions in the percentage of albumin-bound estradiol and an increased percentage of SHBG-bound estradiol, after 3-6 months of tamoxifen; after 12-18 months there was also a significant decrease in the non-protein-bound estradiol fraction. We conclude that in postmenopausal breast cancer patients the redistribution of circulating estradiol, with reduced bioavailability, provides an additional mechanism to those demonstrated previously for the therapeutic activity of tamoxifen. Another 12 patients receiving tamoxifen and 8 who were not were followed for 6-12 months on a low-fat diet (fat comprised 20% of the total calories). The dietary intervention had no effect on the serum SHBG concentration or the estradiol distribution. Although tamoxifen increased the serum corticosteroid-binding globulin and partially suppressed the follicle-stimulating hormone concentrations, the responses obtained were less consistent compared with those of the SHBG levels.

Biological Availability↗

PubMed2003

Estradiol attenuates programmed cell death after stroke-like injury.

Estradiol is a known neurotrophic and neuroprotective factor. Our previous work demonstrated that replacement with physiological concentrations of estradiol protects the cortex against middle cerebral artery occlusion (MCAO)-induced cell death. The cerebral cortex exhibits caspase-dependent programmed cell death (PCD) in many models of focal cerebral ischemia. We hypothesized that estradiol attenuates PCD during stroke injury. The current study explored the temporospatial pattern of markers of PCD, their relationship to the evolution of injury, and their modulation by estradiol. Rats were ovariectomized and treated with either estradiol or vehicle. One week later, rats underwent MCAO, and brains were collected at 1, 4, 8, 16, and 24 hr. We assessed the temporospatial evolution of infarction volume, DNA fragmentation, and levels of spectrin cleavage products in ischemic cortex. Estradiol led to a delay and attenuation of injury-mediated DNA fragmentation as early as 8 hr after MCAO. Estradiol also dramatically reduced the level of the 120 kDa caspase-mediated spectrin breakdown product (SBDP120) at 4 hr but not at 8 or 16 hr. The SBDP150, produced by caspase and calpain, showed peak levels at 16 hr but was not altered by estradiol. These results strongly suggest that estradiol protects the ischemic cortex by attenuating PCD, thereby reducing caspase activity, DNA fragmentation, and subsequently, overall cell death. These studies deepen our understanding of the mechanisms underlying estrogen-mediated neuroprotection.

Animals↗

PubMed2004

[Effects of estradiol on deltamethrin-induced neurotoxicity in rat cerebro-cortical synaptosomes].

OBJECTIVE: To investigate the neuroprotective effect of estradiol on the release of excitatory amino acid (EAAs) mediator, and the activity of ATPase in cerebro-cortical synaptosome membrane of rats exposed to deltamethrin. METHODS: Using HPLC to detect EAAs release, and colorimeter method to measure the activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, Ca(2+)-Mg(2+)-ATPase in the cerebro-cortical synaptosomes of ovariectomized rats exposed to deltamethrin (2 x 10(-5)mol/L), and treated with different doses of 17beta estradiol (10(-5), 10(-8), 10(-11) mol/L). Meanwhile, the estrogen receptor (ER) antagonist, tamoxifen, was used to investigate the effect on estradiol. RESULTS: The release of Asp and Glu from the cerebro-cortical synaptosomes was significantly increased by 2 x 10(-5)mol/L deltamethrin exposure at the depolarizing state evoked by 50 mmol/L KCl, while 10(-8), 10(-11) mol/L 17beta estradiol could partly inhibit the effect of deltamethrin on the release of Asp (28.42%, 24.36%, respectively), Glu (21.52%, 14.57%, respectively). The activities of 4 kinds of ATPase were inhibited by 2 x 10(-4) mol/L deltamethrin, and these effects could be blocked by 10(-5) mol/L estradiol, while the activity of Ca(2+)-ATPase was increased by 10(-8), 10(-11) mol/L of estradiol. However, no obvious antagonistic effect of tamoxifen on the function of estradial on EAAs release or the activities of ATPase was found. CONCLUSION: Estradiol showed certain neuroprotective effect on the release of EAAs and the inhibition on ATPase induced by deltamethrin. The effect of estradiol on synaptosomes may indicate the nongenetic mechanism of estradiol.

Animals↗