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 973 records · Page 54Linked to original sources
PubMed1999

Differential membrane antioxidant effects of immediate and long-term estradiol treatment of MCF-7 breast cancer cells.

Previous studies have documented the direct antioxidant effects of estradiol, and it is tempting to ascribe the antiapoptosis effects of estradiol to its scavenging of reactive oxygen species. However, recent reports have also demonstrated that long-term exposure of MCF-7 human breast cancer cells to estradiol results in estrogen receptor- and estradiol dose-dependent overexpression of the antiapoptosis gene, bcl-2. We have used the pattern of protection of membrane phospholipids from oxidation as a probe to separate these direct and indirect effects of estradiol from one another. Immediate exposure to estradiol non-specifically protects all membrane phospholipids from oxidation by the diazo radical initiator, AMVN. This implies the direct antioxidant activity of estradiol in this system. In contrast, long-term exposure, with associated increased expression of bcl-2, protects only phosphatidylserine, the oxidation of which is a critical component of the final common pathway for apoptosis. This bcl-2-mediated indirect effect of estradiol is accompanied by prevention of apoptosis in MCF-7 cells.

Antioxidants↗
PubMed1994

The influence of body condition on 17-beta estradiol levels in relation to vitellogenesis in female Vipera aspis (Reptilia, Viperidae).

Seventy-six wild Vipera aspis females were caught over 3 years and placed in outdoor enclosures; 39 reproduced and 37 did not. Almost all the reproductive females had a body condition index (BCI) greater than 0.70 when vitellogenesis began. Monthly blood samples were taken by cardiac puncture. The main plasma parameters of vitellogenesis were measured by spectrophotometry: total plasma calcium, phosphorus, phospholipids, cholesterol, triglycerides, proteins, and albumin. Plasma 17-beta estradiol levels were determined by RIA. Vitellogenesis started soon after hibernation in reproductive females with very high 17-beta estradiol concentrations (average of 4.00 ng/ml) and there was a marked mobilization of maternal reserves (fat bodies, liver, and vertebral bone) associated with very high values of plasma calcium, phosphorus, phospholipids, cholesterol, triglycerides, and proteins. The kinetics of the main plasma components were described throughout the vitellogenesis period (from March to early June), when all plasma parameters differed markedly between reproductive and nonreproductive females. After ovulation, the differences between the two groups of females disappeared except in the case of albumin, which remained at a very low level in reproductive females for 6 months. All nonreproductive females had low 17-beta estradiol plasma levels during vitellogenesis (average of 0.08 ng/ml) and there was no suggestion of mobilization of maternal reserves. After vitellogenesis plasma concentrations of estradiol were low in reproductive (an average of 0.08 ng/ml) and in nonreproductive animals (0.06 ng/ml). Five nonreproductive females kept in the laboratory were estrogenized by 17-beta estradiol silastic implants. The 17-beta estradiol concentrations were close to those measured in reproductive females during vitellogenesis. Maternal reserves were mobilized, with almost all metabolic parameters exhibiting the vitellogenic pattern. When the silastic implants were removed, 17-beta estradiol concentrations dropped sharply to a basal level, but the other components were maintained near the vitellogenic values for several months. In contrast to previous studies on viviparous snakes, these results suggest that in V. aspis 17-beta estradiol levels are linked strictly to vitellogenesis.

Animals↗
PubMed1999

Fertility decline in aging roosters is related to increased testicular and plasma levels of estradiol.

The relationships between testicular and plasma hormone levels and the decline in fertility in aging roosters were examined. Body mass, testicular mass, and fertility were measured in roosters from 20 to 72 weeks of age. Plasma was assayed for LH and testosterone, and estradiol and testicular extracts were assayed for testosterone and estradiol contents. Fertility increased rapidly in young roosters to a peak of 96.2 +/- 3.9% at 37 weeks of age. Thereafter, fertility declined and by 72 weeks of age was significantly lower than at 37 weeks. Plasma LH reached 16.8 +/- 2.5 ng/ml at 27 weeks and remained high until 60 weeks of age, when it decreased significantly. Plasma and testicular testosterone levels increased from low levels in young birds to a peak that coincided with highest fertility and declined thereafter. Plasma and testicular estradiol showed a striking inverse relationship with testosterone. Plasma estradiol was 29.4 +/- 4.0 pg/ml in 20-week-old birds, decreased rapidly as testosterone increased, and increased again in older birds as testosterone decreased. Thus, the decline in fertility in aging roosters was associated with a decrease in plasma LH and testosterone and an increase in plasma and testicular estradiol. It is suggested that plasma levels of LH and testosterone in roosters are regulated by a negative feedback mechanism involving estradiol that is produced not only by the aromatization of testosterone in the brain but also by peripheral estradiol originating in the testes and that estradiol has a major role in the decline in fertility in aging roosters.

Aging↗
PubMed1999

Estradiol accelerates extinction of lithium chloride-induced conditioned taste aversions through its illness-associated properties.

Estradiol accelerates extinction of LiCl-induced conditioned taste aversions when it is present during a period that starts 2-3 days after acquisition and extends throughout extinction (before and during extinction). It has been suggested that estradiol acts before, not during, extinction and that its effect on extinction is associated with its illness-inducing properties. This hypothesis is based on previous work which shows an attenuation of conditioned taste aversion learning when rats are exposed to illness-inducing agents during a period that starts 2 days after acquisition and ends 2 days before extinction trials are initiated. Four experiments were designed to test elements of this hypothesis. The first two experiments demonstrated that if an estradiol-filled Silastic capsule is implanted before extinction of a LiCl-induced aversion, when the conditioned taste is not present, it accelerates extinction, but if it is implanted during extinction, when the conditioned taste is present, it prolongs extinction. The third experiment showed that the same dose of estradiol that accelerates extinction of a LiCl-induced aversion was effective in producing a conditioned taste aversion when it was present for 18 h after consumption of a novel sucrose solution. The fourth experiment indicated that serum levels of estradiol were elevated during the 18 h. These results are consistent with the hypothesis that the acceleration of extinction by estradiol is associated with its illness-inducing properties. It is suggested that estradiol acts on neural areas that mediate illness information and that one of these areas, the area postrema is necessary for estradiol to accelerate extinction of a LiCl-induced aversion.

Analysis of Variance↗
PubMed1997

Posttraining estradiol injections enhance memory in ovariectomized rats: cholinergic blockade and synergism.

The present experiments examined acute posttraining estrogenic influences on memory in ovariectomized rats. In experiment 1 rats received a single 8-trial (30-s ITI) training session with a submerged escape platform located in the same quadrant of a circular water maze on all trials. Following trial 8, rats received a posttraining intraperitoneal injection of either an estradiol-cyclodextrin inclusion complex (0.1, 0.2, or 0.4 mg/kg) or saline. On a retention test session 24 h later, the escape latencies of rats given injections of estradiol (0.2 mg/kg) were significantly lower than those of saline-treated rats, indicating an enhancement of memory. Injections of estradiol delayed 2 h posttraining did not affect retention, demonstrating a time-dependent effect of estradiol on memory storage processes. In experiment 2a, posttraining injections of the cholinergic muscarinic receptor antagonist scopolamine (0.4 mg/kg) impaired memory in ovariectomized rats. In experiment 2b, the memory-enhancing effect of estradiol (0.2 mg/kg) was blocked by concurrent posttraining administration of a subeffective dose (0.1 mg/kg) of scopolamine, suggesting an interaction between estradiol and muscarinic cholinergic systems in memory modulation. In experiment 3a, posttraining injections of the cholinergic muscarinic receptor agonist oxotremorine (0.2 mg/kg) enhanced memory in ovariectomized rats. In experiment 3b, concurrent posttraining injection a subeffective dose of estradiol (0.1 mg/kg) and a subeffective dose of oxotremorine (0.1 mg/kg) enhanced memory, indicating a synergistic effect of estradiol and muscarinic receptor activation on memory.

Animals↗
PubMed1980

Multistage functional system amplifying and spreading the effect of estradiol in rat uterus.

Estradiol is demonstrated to induce histidine decarboxylase, and histamine is shown to activate adenylate cyclase in rat uterus. Histamine and cyclic 3',5'-AMP mimic the effects of estradiol in that they enhance RNA synthesis, induce glycolytic enzymes and uterus imbibition. The data suggest that estradiol enhances by induction of histidine decarboxylase the formation of histamine, the latter activates adenylate cyclase providing accumulation of cyclic 3',5'-AMP, which, probably, induces glycolytic enzymes through phosphorylation of chromatin proteins, and mediates other estradiol effects. The chain of successively acting enzymes and mediators constitutes, obviously, a cascade amplifying estradiol action. Since histamine is known to act as an intercellular mediator, attempts were made to find out the distribution of estradiol histamine and cyclic 3',5'-AMP among uterus cells. Autoradiography has shown that [3H]-estradiol is bound by the nuclei of myometrium cells, [3H]-histamine was found above the cytoplasm of these cells, E13H]-cyclic 3',5'-AMP is selectively bound by the cells of capillary endothelium of the uterus. The estradiol mediators seem to spread effect of hormone on cells of different types which form together a kind of multicellular functional system.

Adenylyl Cyclases↗
PubMedDate not supplied

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

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

Adult↗
PubMed1998

Estradiol enhances gene delivery to human breast tumor cells.

The influence of estradiol on the delivery of plasmid DNA to estrogen receptor positive MCF-7 human breast cancer cells was studied by the use of a reporter assay and by histochemical staining. Continuous exposure to estradiol enhanced the lipofectamine-mediated delivery of both pSV40-luciferase and pCMV beta-galactosidase in a concentration-dependent manner. Estradiol increased both the amount of pCMV beta-galactosidase per cell and the total fraction of cells competent to receive the transgene. The efficiency of transgene delivery to MCF-7 cells was further improved by repeating the transfection procedure in the presence of estradiol. Although overall gene uptake was reduced in control cells when studies were performed at room temperature (as opposed to 37 degrees C), potentiation of gene uptake by estradiol was maintained. At a concentration of 100 microM, estradiol also enhanced delivery of the transgene to estrogen receptor negative MDA-MB-231 breast tumor cells, indicating that the potentiating effects of estradiol are not mediated through the estrogen receptor. These studies are the first to raise the possibility that gene delivery to breast tumor cells can be improved by estradiol in single- or repeated-treatment regimens.

Breast Neoplasms↗
PubMed1999

Matrix delivery transdermal 17beta-estradiol for the prevention of bone loss in postmenopausal women. The International Study Group.

A total of 277 early postmenopausal women were enrolled in this placebo-controlled 2-year study to examine the efficacy of a matrix transdermal 17beta-estradiol system, at three different dosages (25, 50 and 75 mg/day) combined with sequential oral dydrogesterone 20 mg/day, in preventing bone loss. At 2 years, the difference from placebo in percentage change from baseline of L1-4 lumbar spine bone mineral density (BMD) (assessed by dual-energy X-ray absorptiometry) was 4.7% +/- 0.7% with estradiol 25 mg/day, 7.3% +/- 0.7% with estradiol 50 mg/day and 8.7% +/- 0.7% with estradiol 75 mg/day (all values mean +/- SEM). There were also significant increases in femoral neck, trochanter and total hip BMD with all doses of estradiol compared with placebo. Additionally, most patients had a significant gain (increase greater than 2.08%) in lumbar spine bone mass compared with placebo. Patients who received estradiol also experienced clinically significant and dose-related decreases in total serum osteocalcin, serum bone alkaline phosphatase and urinary C-telopeptide, with all three markers of bone turnover returning to premenopausal levels. Estradiol was well tolerated during the 2-year treatment period. Transdermal estradiol is effective and well tolerated at dosages between 25-75 mg/day in the prevention of bone loss in postmenopausal women; 25 mg/day offers an effective option for those women who cannot tolerate higher doses.

Administration, Cutaneous↗
PubMed2005

17beta-Estradiol inhibits calcium-dependent, but not calcium-independent, contraction in isolated rat aorta.

It is now well known that 17beta-estradiol has an endothelium-independent, non-genomic vasorelaxant effect. We hypothesized that 17beta-estradiol has its non-genomic effect on calcium-independent contraction in de-endothelialized rat aortic rings. Rat aortic ring preparations were mounted in organ baths and exposed to contractile agents. 17beta-Estradiol (8, 20 or 50 microM), but not 17alpha-estradiol, concentration-dependently decreased the tension induced by 1.0 microM phenylephrine (PE) in the presence, but not in the absence, of calcium in the solution. Pretreatment with 17beta-estradiol concentration-dependently inhibited vascular contractions induced by cumulative addition of PE or calcium and almost completely abolished those induced by cumulative addition of Bay K8644, a calcium channel opener. Furthermore, 17beta-estradiol also concentration-dependently decreased the tension induced by 0.3 microM phorbol 12,13-dibutyrate (PDBu), a protein kinase C activator, in the presence of calcium in the solution, but not in the absence of calcium in the solution. Pretreatment with 17beta-estradiol had little effect on vascular contractions induced by PDBu or PE or on PE-induced mitogen-activated protein kinase (MAPK) activation in calcium-free Krebs solution. These results suggest that 17beta-estradiol inhibits calcium-dependent, but not calcium-independent, vascular contraction.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2005

Surface plasmon resonance-based immunoassay for 17beta-estradiol and its application to the measurement of estrogen receptor-binding activity.

A rapid and simple surface plasmon resonance (SPR)-based immunoassay for detection of 17beta-estradiol was developed. The assay was designed as an inhibitive format, in which 17beta-estradiol-BSA conjugates are immobilized on an SPR sensor chip and the binding of antibody to the chip is measured. The binding was inhibited by 17beta-estradiol in the concentration range 0.468 to 21.4 nmol L-1 with an IC50 value of 2.29+/-0.10 nmol L-1. Although not as sensitive as traditional radioimmunoassay (RIA) and enzyme-linked immunoassay (ELISA), this method requires no separation and washing after addition of the antibody, steps which are relatively time-consuming. Estrogen receptor (ER)-binding was then investigated using this SPR immunoassay for the determination of the amount of unbound 17beta-estradiol after competition with test compounds for the ER-binding. Inhibition of the binding of 17beta-estradiol to ER by diethylstilbestrol (DES) was successfully measured by injecting the reaction mixture into the SPR sensor after addition of the antibody. This binding assay requires no separation of unbound 17beta-estradiol from the mixture and no radioisotope- or fluorescence-labeling of 17beta-estradiol. These results show the potential usefulness of the SPR sensor both detecting 17beta-estradiol and evaluating the ER-binding activity of xenoestrogens such as DES in a single assay system.

Animals↗
PubMed1987

Serum estradiol and coronary artery disease.

Serum estradiol levels were measured in 300 men undergoing coronary angiography. Among these men, there were no significant differences in the serum estradiol levels between patients with (mean, 26.4 pg/ml) and those without (mean, 30.9 pg/ml) angiographically confirmed coronary artery disease. There were no significant differences in any of the established coronary risk factors when patients were subdivided according to the presence or absence of coronary artery disease or according to the extent of disease. In addition, no significant correlation was noted between mean serum estradiol levels and the extent of coronary artery disease as classified by the number of obstructed coronary vessels. A matched-pairs analysis was carried out in which patients who had normal coronary arteries were matched with those who had coronary artery disease on the basis of age, cigarette smoking, prior history of myocardial infarction, and body mass index. The mean serum estradiol level in the patients with coronary artery disease was 28.7 pg/ml, and the mean estradiol level was 31.4 pg/ml for the matched patients with normal coronary arteries. In addition, when serial (three) estradiol determinations were carried out in 100 patients, no association was observed between degree of estradiol variability and the occurrence and/or extent of coronary artery disease. The results of this observational study fail to support an association between serum estradiol levels and the presence or degree of coronary artery disease in men as documented by coronary angiography.

Adult↗
PubMed1983

Differential lipemic and hormonal responses to oral and parenteral 17 beta-estradiol in postmenopausal women.

To determine the influence of the route of administration on the hormonal and lipemic responses to 17 beta-estradiol, 50 postmenopausal women were studied before and after various regimens of replacement therapy. The effects on plasma lipids and lipoproteins and on estrone and estradiol levels of the oral administration of micronized estradiol or estradiol valerate (2 mg/24 hours) were compared to those of percutaneously administered estradiol (3 mg/24 hours). These treatments were given during two cycles of 3 weeks separated by a 1-week interval. Circulating levels of estradiol and estrone increased significantly (p less than 0.05) in all groups while follicle-stimulating hormone levels decreased significantly. The posttreatment estradiol/estrone ratio was significantly (p less than 0.05) greater in the parenteral group (0.8 +/- 0.1) than in both oral estrogen groups (0.3 +/- 0.1 and 0.4 +/- 0.1, respectively). Oral administration of estradiol resulted in a significant increase in triglycerides (20% to 44%, p less than 0.05) and very low-density lipoprotein (VLDL) triglycerides (30% to 40%, p less than 0.05) and a decrease in low-density lipoprotein cholesterol (14% to 17%, p less than 0.05). In contrast, despite a substantial increase in serum estrogen levels, percutaneous estradiol induced a significant decrease in triglyceride (from 0.78 +/- 0.04 to 0.67 +/- 0.05 mmol/L, p less than 0.001) and VLDL triglyceride (from 0.44 +/- 0.16 to 0.35 +/- 0.12 mmol/L p less than 0.05) levels and no significant change in cholesterol levels. The increases of high-density lipoprotein cholesterol levels observed in the three groups were not significant. These data indicate that the route of administration modulates the metabolic and hormonal responses to estrogen therapy.

Administration, Oral↗
PubMed1986

Maternal estradiol response to alterations in uteroplacental blood flow.

Low levels of maternal estrogens are commonly regarded as indicators of fetal stress. We continuously monitored distal aortic blood flow by flowmeter, fetal heart rate, and amniotic fluid pressure in seven pregnant baboons near term. Four of the animals received a constant intravenous infusion of [7-3H]dehydroepiandrosterone and [4-14C]estradiol for 270 minutes. A 50% reduction in mean distal aortic blood flow was imposed after 60 minutes by means of partial occlusion of the aorta with a snare device and released at 180 minutes. Blood was collected at 10-minute intervals from 30 to 60 minutes, 120 to 180 minutes, and 240 to 270 minutes. Concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate, estradiol, and cortisol in maternal plasma were determined by radioimmunoassay. Metabolic clearance rates of dehydroepiandrosterone and estradiol were calculated from plasma concentrations of [3H]dehydroepiandrosterone and [14C]estradiol. There was no significant change in maternal levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, or cortisol with alterations in distal aortic blood flow. Three animals exhibited no fetal heart rate evidence of fetal stress; estradiol levels declined during occlusion and returned toward control after release of the snare. Four animals exhibited repetitive late decelerations under conditions of reduced flow; estradiol was unchanged or rose slightly during occlusion but increased three- to 10-fold after release whereas the metabolic clearance rate of both dehydroepiandrosterone and estradiol remained stable. We conclude that placental hypoperfusion without fetal stress results in decreased conversion of aromatizable substrate and elevated maternal estradiol levels during acute hypoxemic fetal stress probably represent increased production of fetal androgen.

Animals↗
PubMed1989

Treatment of oophorectomized guinea pigs with intrauterine 17 beta-estradiol pellets may modulate myometrial beta-adrenergic receptor binding properties.

Intrauterine 17 beta-estradiol pellets can induce an up-regulation of guinea pig myometrial beta-adrenergic receptor density and l-isoproterenol-dependent adenylate cyclase activity. Does 17 beta-estradiol influence the ability of beta-adrenergic receptors to form a "high affinity" state with l-isoproterenol, which is a necessary step for adenylate cyclase activation? Nonpregnant, oophorectomized guinea pigs received intrauterine pellets of either placebo, 17 beta-estradiol, progesterone, or 17 beta-estradiol plus progesterone for 1 week. 17 beta-Estradiol resulted in pharmacologic, whereas progesterone resulted in physiologic plasma 17 beta-estradiol and progesterone concentrations, respectively. The affinity of myometrial beta-adrenergic receptors for l-isoproterenol was measured by percentage of inhibition of -[125I]cyanopindolol binding. In all groups, the competition curves in the presence of magnesium chloride could be resolved into two affinity states of the beta-adrenergic receptor, "high" and "low," respectively. The ratio of their dissociation constants was not influenced by hormonal treatment. However, the relative concentration of beta-adrenergic receptors in the high affinity state was significantly higher in the 17 beta-estradiol-treated group than that in the control group. This correlates with the up-regulation in myometrial adenylate cyclase activity and suggests that myometrial beta-adrenergic receptor-adenylate cyclase function may be modulated by 17 beta-estradiol.

Adrenergic beta-Antagonists↗
PubMed1986

Effects of high-dose ethinyl estradiol on serum concentrations and hepatic secretion of the very-low-density lipoprotein, triacylglycerol, cholesterol, and apolipoprotein A-I in the rat.

Female and male rats were treated with ethinyl estradiol (5.0 mg/kg daily for 5 days). Control animals were pair fed to compensate for the reduction in food intake induced by the estrogen, or were fed ad libitum. Treatment with ethinyl estradiol reduced total cholesterol and apolipoprotein A-I concentrations in the serum of female and male animals. The concentrations of serum and hepatic triacylglycerol were depressed markedly in animals of both sexes in groups treated with ethinyl estradiol, compared to the control group fed ad libitum. Compared to the pair-fed controls, however, ethinyl estradiol had only a very minor further reduction on serum triacylglycerol concentration. In male and female rats, the synthesis and secretion of triacylglycerol by the liver was, in comparison to the pair-fed controls, stimulated by estrogen, whereas the secretion of unesterified cholesterol was unaffected by any of the treatment regimens. The synthesis and secretion of total cholesteryl esters by livers from male and female rats was increased by treatment with ethinyl estradiol. The hepatic synthesis and secretion of VLDL triacylglycerol and cholesteryl ester was stimulated by ethinyl estradiol in male and female rats, and the VLDL particle was enriched with cholesteryl ester. Treatment with the high-dose estrogen increased the secretion of apolipoprotein A-I by livers from female rats. It is suggested that the depression in the serum concentrations of cholesteryl esters and apolipoprotein A-I is the result of increased rates of hepatic and/or peripheral catabolism of these components and that the hepatic production rates were increased or unaffected in animals administered high doses of ethinyl estradiol. Since the secretion of apolipoprotein A-I by livers from male rats was unaffected by treatment with ethinyl estradiol, the response to estrogen may be sex related.

Animals↗
PubMed1996

Similarities and differences in the glucuronidation of estradiol and estrone by UDP-glucuronosyltransferase in liver microsomes from male and female rats.

In this study, we evaluated the effects of pH, in vitro inhibitors, in vivo enzyme inducers, age, and sex on the glucuronidation of estradiol and estrone by rat liver microsomes. Although the pH dependence curves for the glucuronidation of estradiol and estrone were similar, the pH dependence curves for these estrogens by liver microsomes from adult male rats were very different from those by liver microsomes from adult female rats. These results suggest that liver microsomes from adult male and have different estrogen glucuronosyltransferases. Liver microsomes from immature or adult female rats catalyzed the glucuronidation of estrone and estradiol more rapidly than liver microsomes from age-matched male rats. Intraperitoneal injection of sodium phenobarbital (75 mg/kg/day) or dexamethasone (75 mg/kg/day) into immature or adult male or female rats for 3-4 days resulted in a 33-58% increase in liver microsomal glucuronosyltransferase activity for estradiol, but there was little or no stimulatory effect on glucuronosyltransferase activity for estrone. Treatment of immature or adult male or female rats with 3-methylcholanthrene (25 mg/kg/day) for 3-4 days did not stimulate liver microsomal glucuronosyltransferase activity for estradiol or estrone, but the glucuronidation of 4-nitrophenol was stimulated several-fold. The in vitro addition of testosterone had a strong inhibitory effect on the glucuronidation of estradiol and estrone by liver microsomes from both adult male and female rats, whereas the in vitro addition of 4-nitrophenol had a slightly greater inhibitory effect on the glucuronidation of estradiol and estrone by adult male liver microsomes than by adult female liver microsomes. In conclusion, our results suggest that male and female rat livers have different estrogen glucuronosyltransferases and that the glucuronidation of estradiol, estrone, and 4-nitrophenol is catalyzed by different glucuronosyltransferases that are under different regulatory control.

Animals↗
PubMed1977

Binding of [3H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by experimental diabetes.

In streptozotocin-diabetic female rats acute (24 h) withdrawal of insulin significantly impairs both estradiol + progesterone-induced sexual receptivity and cell nuclear concentration of [3H]estradiol in hypothalamus, preoptic area, and pituitary gland. Omission of insulin treatment for the first 24 h of a 30-h or 54-h estradiol benzoate-conditioning period significantly reduced mean lordosis ratings of ovariectomized-diabetic rats. Insulin withdrawal at the time of progesterone treatment and behavioral testing did not diminish sexual receptivity. One-half or 2 h after an intravenous injection of [3H]estradiol-17beta diabetic rats without insulin exhibited reduced cell nuclear [3H]estradiol concentrations (2 h) and/or diminished cell nuclear/whole homogenate concentration ratios (0.5 and 2 h). Twenty-four hour insulin withdrawal affected neither whole tissue [3H]estradiol uptake nor hypothalamus-preoptic area cytoplasmic estrogen-receptor content. These results: (1) suggest that diminished estradiol binding by target tissue cell nuclei may contribute to the well-known reproductive failures of female diabetics, and (2) support the concept that estradiol acts at the level of brain cell nuclei to induce female sexual behavior.

Animals↗