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PubMed1982

Prolactin and estradiol increase striatal dopamine receptor density in intact, castrated and hypophysectomized rats.

1. Ovariectomized female or intact male rats were implanted with three adenohypophyses under the kidney capsule or treated with 17 beta-estradiol (10 micrograms twice daily) for 2 weeks. 2. In animals of both sexes, the pituitary-implanted and estradiol-treated rats had elevated plasma prolactin levels and had increased levels of striatal dopamine receptors. 3. We next investigated the possibility of an indirect action of estradiol via prolactin using hypophysectomized female rats (hypox) treated with 17 beta-estradiol or ovine prolactin (500 micrograms, twice daily) for 5 days. 4. Striatal dopamine receptor concentration was lower in hypox animals as compared to ovariectomized (85%, p less than 0.05) or intact female rats at random stage of the estrous cycle (76%, p less than 0.05) while the affinity (KD) of [3H]spiperone for these dopaminergic sites remained unchanged. 5. Treatment with estradiol or prolactin increased the level of striatal dopamine receptors (HYPOX + estradiol: 144% vs HYPOX, p less than 0.05; HYPOX + prolactin: 147% vs HYPOX, p less than 0.05). 6. These results indicate that high prolactin levels induced by pituitary implants or by injections of ovine prolactin lead, as observed with chronic estradiol treatment, to an increased density of striatal dopamine receptors. However, the effect of estradiol may not be explained exclusively by increased prolactin levels since the supersensitivity is also observed in hypophysectomized animals.

Animals↗
PubMed2001

Estradiol levels in psychotic disorders.

Estradiol has been postulated to constitute a protective factor for schizophrenia, which could provide women at risk to experience a psychotic episode with a relative protection in phases of high estradiol levels, i.e. before menopause and during the peri- and postovulatory phases of their cycle. Women suffering from schizophrenia have been reported to show significantly lower estradiol levels than the normal population and to experience first onset or recurrence of a psychotic episode significantly more often in low estrogen phases of the cycle with low estradiol levels. We examined estradiol levels in an open prospective study in 43 women admitted with a diagnosis of an acute psychotic episode and could confirm these findings for schizophrenia as well as other psychotic disorders. Only 28% of the women exhibited estradiol and progesterone levels indicating a peri- or postovulatory phase and all of the estradiol levels on admission were either within the lower part of the cycle-dependent normal range or below normal; comparison with a control group of healthy volunteers and patients admitted with different psychiatric diagnoses confirmed their estradiol levels to be significantly higher. However, when splitting this control group, the statistical difference would only hold between the study group of psychotic patients and the healthy control group. The group of patients with other diagnoses than a psychotic episode fell in between of the other two groups and did not differ significantly from either. Thus, an unspecific effect, i.e. a hypothalamic downregulation due to the stress of acute hospitalization must be born in mind when assessing hormone levels in acutely psychotic women.

Adult↗
PubMed1999

Evidence for attenuation of gonadotropin pulse frequency in hypergonadotropic women with estradiol secretion in the menopausal transition.

To investigate neuroendocrine interventions for climacteric symptoms in peri- and post-menopausal periods, the association between endocrine status and symptoms was examined in 519 peri- and post-menopausal women with climacteric symptoms. Furthermore, we evaluated the nature of putative disturbances in pulsatile gonadotropin (FSH and LH) secretion in 14 hypergonadotropic women with estradiol secretion and 16 hypergonadotropic women with hypoestrinism. We observed that 68.6% (356/519) of women with climacteric symptoms and 49.2% (121/246) of women in good health showed hypergonadotropinemia, and that 39.3% (140/356) of hypergonadotropic women with climacteric symptoms and 23.1% (28/121) of healthy women (controls) showed estradiol secretion (p < .002). In particular, the endocrinological profile of hypergonadotropinemia with estradiol secretion was observed in 67.1% (60/92) of pre-menopausal women with climacteric symptoms, approximately 2 x higher than that in healthy women (p < .005). Mental symptoms were observed at a significantly higher incidence in women with the endocrinological profile of hypergonadotropinemia with estradiol secretion compared with that in women with hypergonadotropic hypoestrinism showing a symptomatic profile, namely 25.0 versus 6.9% for mood lability (p < .001), and 21.4 versus 9.3% for anxiety symptoms (p < .001). Moreover, in vivo FSH and LH pulse frequencies were observed in only 14.3 and 18.6% of women with hypergonadotropinemia with estradiol secretion whereas such pulses were observed in all women with hypergonadotropic hypoestrinism. We also observed FSH and LH pulse frequencies in hypergonadotropinemia with estradiol secretion 0.14 +/- 0.35 and 0.29 +/- 0.45/3 h, respectively compared with those in hypergonadotropinemia without estradiol secretion 2.25 +/- 0.91 and 2.81 +/- 0.73/3 h, respectively (p < .001). Such findings are considered to be consistent with diminished hypothalamic GnRH impulse strength. In summary, we infer that decreased pulse frequencies in FSH and LH secretion are due to decreased hypothalamic GnRH impulse strength in women with the endocrinological profile of hypergonadotropinemia with estradiol secretion. As the potential mechanisms of this finding, it should be considered that specific endocrine environments damage the pulse generator mechanism in the diencephalon, and that changes occur in the pituitary responsiveness to GnRH (changes in receptor function).

Adult↗
PubMedDate not supplied

Estradiol induction of cAMP in breast cancer cells is mediated by foetal calf serum (FCS) and sex hormone-binding globulin (SHBG).

Plasma sex hormone-binding globulin (SHBG or SBP), the specific carrier for estradiol and androgens, after binding to its membrane receptor (SHBG-R), causes a significant increase of cAMP in the presence of estradiol, in both breast (MCF-7) and prostate (LNCaP) cancer cells maintained in serum-free medium. On the other hand, it has been proposed that estrogens, in addition to the well-known nuclear receptor pathway, exert their biological effect inducing cAMP, as a consequence of a direct membrane action, in breast cancer and uterine cells. The aim of the present study was to clarify this controversial issue by verifying if the cAMP increase in MCF-7 cells was a direct effect of estradiol, or if it was mediated by FCS proteins, such as bovine sex hormone-binding globulin; and to reevaluate the effect of human SHBG on cAMP induction in the presence of FCS. MCF-7 cells were maintained in DCC-FCS (treated with DCC to remove steroids), in SHBG-FREE/DCC-FCS (treated with DCC and with a specific affinity chromatography to remove bovine sex hormone-binding globulin), or in serum-free medium (SFM). It was observed that estradiol determined a significant time-dependent increase of cAMP only in MCF-7 cells maintained in 10% DCC-FCS. When cells were maintained in 10% SHBG-FREE/DCC-FCS, estradiol had no detectable effect. However, its ability to increase cAMP was observed again after the addition of human SHBG, in doses ranging from 5 to 50 nM. Moreover, in the presence of 10% SHBG-FREE/DCC-FCS, SHBG, even in the absence of estradiol, caused a significant increase of cAMP. In conclusion, the data reported in the present study suggest that the ability of estradiol to induce cAMP in MCF-7 cells is not due to a direct membrane effect of the hormone, but rather it is mediated by FCS. SHBG is one of the serum factors mediating estradiol action. Lastly, it was proven that SHBG triggers the cAMP pathway in MCF-7 cells in a physiologic culture condition and at physiologic concentrations.

Animals↗
PubMed2003

Mechanism of the salutary effects of 17beta-estradiol following trauma-hemorrhage: direct downregulation of Kupffer cell proinflammatory cytokine production.

Kupffer cells have been reported as a major source of proinflammatory cytokines (i.e. IL-6, TNF-alpha), which have been implicated in the pathogenesis of trauma-hemorrhage. Previous studies have shown a protective effect of 17beta-estradiol on immune function and physiological responses following trauma-hemorrhage. In this study, we investigated whether 17beta-estradiol has a direct effect on Kupffer cell cytokine production following trauma-hemorrhage. Male Sprague-Dawley rats were subjected to trauma (midline laparotomy) and hemorrhage (35-40 mmHg for 90 min followed by fluid resuscitation) or sham operation. Two hours later, Kupffer cells were isolated and cultured with 17beta-estradiol in the presence and absence of lipopolysaccharide stimulation. Kupffer cell IL-6 and TNF-alpha production increased following trauma-hemorrhage. Incubation with 17beta-estradiol attenuated the production of IL-6 by cells from both sham and trauma-hemorrhage animals in a dose-dependent manner. The suppression of IL-6 production by 17beta-estradiol was paralleled by a decrease in mRNA levels. In contrast to IL-6, the effects of 17beta-estradiol on TNF-alpha production were minimal. In conclusion, these results indicate the direct downregulation of Kupffer cell IL-6 production by 17beta-estradiol at a molecular level, which might explain in part the previously observed salutary effects of estradiol treatment following trauma-hemorrhage.

Animals↗
PubMed1996

Estradiol treatment transiently increases trabecular bone volume in ovariectomized rats.

The effect of short-term estradiol treatment, administered from the time of ovariectomy, on increased bone turnover and subsequent bone loss was studied in the rat. Adult female Sprague-Dawley rats were ovariectomized and administered daily subcutaneous (s.c.) injections of 17 beta-estradiol at 8 micrograms/ kg per day (Low) and 20 micrograms/kg per day (High) or vehicle alone (Veh). Femoral trabecular bone volume (BV/TV) and trabecular number (Tb.N) in the distal femur were transiently increased at 6 days postoperation in a dose-dependent manner following estradiol administration [mean +/- SEM: BV/TV (%), day 0, 6.6 +/- 0.2; day 6, Veh 7.8 +/- 0.4, Low 10.2 +/- 2.2, High 12.8 +/- 1.7 (p < 0.05); Tb.N (/mm), day 0, 2.30 +/- 0.24; day 6, Veh 2.89 +/- 0.33, Low 3.4 +/- 0.7, High 4.39 +/- 0.34 (p < 0.05)]. Estradiol prevented the ovariectomy-induced decrease in BV/TV and Tb.N between 9 and 15 days observed in Veh rats. Both serum alkaline phosphatase and urine hydroxyproline excretion were maintained at preoperative levels or lower from day 6 postoperation with high dose estradiol. Serum osteocalcin, however, rose above preoperative levels with estradiol at days 6 and 9, but returned to these values on days 15 and 21 postoperation. These results suggest that estradiol, administered from the time of ovariectomy, immediately suppressed markers associated with osteoblast proliferation/matrix synthesis and bone resorption. Mineralization does not appear to be so rapidly suppressed by estradiol with relatively high levels immediately following administration, resulting in a transient increase in trabecular bone volume and trabecular number.

Alkaline Phosphatase↗
PubMed1998

Determinants of tissue estradiol levels and biologic responsiveness in breast tumors.

Estradiol stimulates the growth of breast tumor cells in both pre- and post menopausal women. Following the menopause, the levels of estradiol in breast tumor tissues are similar to those from tumors obtained prior to cessation of ovarian function, even though plasma estrogen levels are 10-50 fold lower in post- than in premenopausal women. These observations suggested the possibility of enhanced estradiol uptake from plasma or in situ synthesis in post-menopausal women. We systematically studied these possibilities in a series of model systems. Initially we demonstrated a very high affinity estradiol binding site in tissues from castrated rats. Enhanced uptake occurred under conditions of low plasma estrogen levels when compared to animals with higher estradiol levels. In situ synthesis also occurred both through the sulfatase and aromatase pathways. In further studies, we compared uptake from plasma with in situ synthesis via aromatase in a nude mouse model. Under the conditions utilized, in situ synthesis resulted in much higher tissue estradiol levels and tumor growth rates than did uptake from plasma. During these studies we demonstrated that tumors deprived of estradiol developed mechanisms rendering them more sensitive to estrogen. This involved the ability of cells to adapt to estradiol deprivation to allow them to be responsive to four log lower amounts of estrogen than when studied under wild type conditions. In addition, cells adapted by increasing their level of aromatase and thus developing the capability to become more sensitive to estrogen precursors. Taken together, these studies demonstrate that breast cancer tissue is highly plastic and can adapt to conditions of estrogen deprivation via a variety of mechanisms.

Animals↗
PubMed1988

Prodrugs for improved oral beta-estradiol bioavailability.

Prodrugs of beta-estradiol (1) were prepared with the objective of improving its oral bioavailability. beta-Estradiol-3-acetylsalicylate (2), beta-estradiol-3-salicylate (3), and beta-estradiol-3-anthranilate (4) were synthesized. With these prodrugs the 3-phenolic hydroxy group of estradiol was protected, so that first-pass conjugative metabolism could be reduced. Prodrug hydrolysis rates in dog and human plasma in vitro were determined. Deacetylation of estradiol-3-acetylsalicylate was much more rapid than its hydrolysis to estradiol. In dogs, oral estradiol bioavailability after administration of 2 and 4 was 17-fold and 5-fold higher, respectively, than after oral 1.

Administration, Oral↗
PubMed1994

Estradiol permeation from nonionic surfactant vesicles through human stratum corneum in vitro.

The permeation of estradiol from vesicular formulations through human stratum corneum was studied in vitro. The vesicles were composed of nonionic n-alkyl polyoxyethylene ether surfactants (CnEOm). The thermodynamic activity of estradiol present in each formulation was kept constant by saturating all formulations with estradiol. The effects of both the particle size and the composition of the formulation on estradiol permeation across excised human stratum corneum were investigated. Stratum corneum that was pretreated with empty surfactant carriers allowed for significantly higher estradiol fluxes compared with untreated stratum corneum. However, estradiol fluxes obtained in these pretreatment experiments appeared to be significantly lower than those obtained by the direct application of the estradiol-saturated carrier formulation on top of the stratum corneum. Furthermore, in the case of pretreatment of the stratum corneum, an increase in carrier size resulted in a decrease in estradiol flux. For direct application the opposite was found. Two mechanisms are proposed to play an important role in vesicle-skin interactions, i.e., the penetration enhancing effect of surfactant molecules and the effect of the vesicular structures that are most likely caused by adsorption of the vesicles at the stratum corneum-suspension interface.

Administration, Cutaneous↗
PubMed2000

Comparative effects of vitamin K2 and estradiol on experimental arteriosclerosis with diabetes mellitus.

In order to further investigate the radical scavenging and anti-arteriosclerotic activities of vitamin K2 and estradiol, the comparative effects of vitamin K2 and estradiol on aortic calcium (Ca) and inorganic phosphorus (P) levels in the aorta and the elastin fraction (fr.) were investigated in male rats after experimental arteriosclerosis with diabetes mellitus was induced by vitamin D2 and radical producing substance, streptozotocin (STZ). Pharmacological dose of vitamin K2 (100 mg/kg b.w.) and medical dose of estradiol (83 micrograms/kg b.w.) suppressed the increased serum glucose, and vitamin K2 and estradiol increased the decrease in serum insulin. Moreover, vitamin K2 and estradiol inhibited the increase of Ca and P in the aorta and the elastin fr. Vitamin K2 and estradiol decreased the increase in serum lipid peroxide (LPO). It is suggested that both the pharmacological dose of vitamin K2 and medical dose of estradiol suppressed the development of arteriosclerosis associated with diabetes mellitus, owing to radical scavenging activity of vitamin K2 and estradiol.

Animals↗
PubMed2002

The value of routine estradiol monitoring in assisted conception cycles.

BACKGROUND: Traditional monitoring of an in vitro fertilization (IVF) treatment cycle includes regular estradiol levels and ultrasound scans in an attempt to reduce the risk of ovarian hyperstimulation syndrome (OHSS). The need for estradiol monitoring remains controversial. METHODS: We reviewed 538 consecutive cycles of IVF that were carried out in our unit to ascertain whether routine estradiol monitoring was of help in preventing OHSS and could be used to predict treatment outcome. Two hundred and sixty-eight patients had their ovarian response monitored with ultrasound (USS) and estradiol levels on the day of hCG administration. The following 270 had USS monitoring but only had an estradiol level checked if they were deemed to be at high risk of OHSS (> 20 follicles on USS or symptomatic). RESULTS: Pregnancy rates per treatment cycle and per embryo transfer were similar in the two groups (all p > 0.05). There were two patients in each group requiring admission to hospital for OHSS. CONCLUSIONS: Estradiol levels did not correlate with IVF outcome. In summary therefore estradiol levels are a poor predictor of treatment success and done routinely do not reduce the incidence of OHSS. It is only necessary to measure the estradiol level in those patients at risk of OHSS on USS monitoring.

Adult↗
PubMed2002

17alpha-estradiol induces aromatase activity in intact human anagen hair follicles ex vivo.

For topical treatment of androgenetic alopecia (AGA) in women, solutions containing either estradiol benzoate, estradiol valerate, 17beta- or 17alpha-estradiol are commercially available in Europe and some studies show an increased anagen and decreased telogen rate after treatment as compared with placebo. At present it is not precisely known how estrogens mediate their beneficial effect on AGA-affected hair follicles. We have shown recently that 17alpha-estradiol is able to diminish the amount of dihydrotestosterone (DHT) formed by human hair follicles after incubation with testosterone, while increasing the concentration of weaker steroids such as estrogens. Because aromatase is involved in the conversion of testosterone to estrogens and because there is some clinical evidence that aromatase activity may be involved in the pathogenesis of AGA, we addressed the question whether aromatase is expressed in human hair follicles and whether 17alpha-estradiol is able to modify the aromatase activity. Herewith we were able to demonstrate that intact, microdissected hair follicles from female donors express considerably more aromatase activity than hair follicles from male donors. Using immunohistochemistry, we detected the aromatase mainly in the epithelial parts of the hair follicle and not in the dermal papilla. Furthermore, we show that in comparison to the controls, we noticed in 17alpha-estradiol-incubated (1 nM) female hair follicles a concentration- and time-dependent increase of aromatase activity (at 24 h: 1 nM = +18%, 100 nM = +25%, 1 micro M = +57%; 24 h: 1 nM = +18%, 48 h: 1 nM = +25%). In conclusion, our ex vivo experiments suggest that under the influence of 17alpha-estradiol an increased conversion of testosterone to 17beta-estradiol and androstendione to estrone takes place, which might explain the beneficial effects of estrogen treatment of AGA.

Adult↗
PubMedDate not supplied

Uterine response to estradiol under action of chorionic gonadotropin in mice.

This work examined the effect of chorionic gonadotropin on proliferative and morphogenetic reactions in the uterus under short- and long-term estrogen treatments. Ovariectomized mice received a single injection with estradiol dipropionate (2 micro g per 100 g; subcutaneously, sc) or vehicle and injections with human chorionic gonadotropin (10 IU per 100 g; sc) or vehicle twice a day for 2 days. Other groups of animals received injections with estradiol once a week or vehicle and injections with chorionic gonadotropin or vehicle once a day for 30 days. The uteri were removed 48 h after the last estradiol or vehicle injection. In animals treated with estradiol and chorionic gonadotropin for a month, the incidence of atypical endometrial hyperplasia was significantly higher. In animals treated with estradiol and chorionic gonadotropin for 2 days or for a month, uterine mass was slightly increased, the number of mitotic cells and BrdU-labeled cells was greater in luminal epithelium, glandular epithelium, stromal and myometrial cells, whereas the expression of estrogen receptors-alpha was lower in all uterine compartments, than in control. In mice who received estradiol and chorionic gonadotropin for 2 days, levels of beta-catenin and glycogen synthase kinase-3beta in luminal and glandular epithelia were lower. In animals treated with estradiol and chorionic gonadotropin for a month, the level of beta-catenin was slightly higher, and the expression of glycogen synthase kinase-3beta was lower in luminal and glandular epithelia. Thus, chorionic gonadotropin exerts estradiol-induced proliferative and morphogenetic changes in the uterus. This action of chorionic gonadotropin is associated with decreased expression of estrogen receptors-alpha and with changes in expression of beta-catenin and glycogen synthase kinase-3beta in the uterus.

Animals↗
PubMed1996

The confirmation of a biochemical marker for women's hormonal migraine: the depo-estradiol challenge test.

PRECIS: Will estrogen withdrawal cause migraines in post-menopausal women? OBJECTIVE: To record the changes in serum estradiol and total estrogen levels after an intramuscular estradiol injection in menopausal subjects and then record any subsequent migraine occurrence. DESIGN: Open selection process, comparative trial. PATIENTS: Twenty-eight postmenopausal women volunteers were given 5 mg depo-estradiol cyprionate as an intramuscular injection. Sixteen (migraine group) had a history of severe, cyclic, menstrually related migraine attacks before becoming menopausal. Twelve (control group) had no history of migraine or headache. All volunteers were on continuous estrogen replacement therapy at the beginning of the study. Progestins were not used in the study. MAIN OUTCOME MEASURES: Serum estradiol and total estrogen levels were measured prior to the depo-estradiol injection and on subsequent days 4, 7, 14, 21, and 28. RESULTS: Total estrogen and estradiol levels varied greatly at every measured interval. Menopausal complaints of vasomotor symptoms were relieved for at least the first 2 weeks of the study. No member of the control group reported a migraine during the month. However, a severe migraine was reported by all 16 women with a history of migraine. The average day of the migraine occurrence was 18.5 +/- 2.8. The serum level of estradiol on the day of the worst migraine was 46.4 +/- 5.6 pg/mL. The significance of these findings was at the 95% confidence level. CONCLUSIONS: This study confirms two factors about menopausal hormonal migraine: (1) it can be precipitated by a drop in serum estrogen levels, and (2) a period of estrogen priming is a necessary prerequisite. This study also identifies that there are two biologically different populations of postmenopausal women: (1) those who developed migraine after a single depo-estradiol injection, and (2) those who did not. By understanding that in addition to the biological predisposition to migraine there exists the biochemical cofactor of falling estrogen levels, we may better understand this phenomenon and develop means to prevent its occurrence.

Adult↗
PubMed1996

Biliary excretion of estradiol-17 beta-glucuronide in the rat.

Estradiol-17beta-glucuronide (E217G) is a cholestatic agent and is considered to be related to the pathogenesis of intrahepatic cholestasis of pregnancy. In the current study, we examined the mechanism of the biliary excretion of E217G and estradiol metabolites in rats. Biliary excretion of tracer doses of [3H]estradiol-17beta-glucuronide and [14C]estradiol or [3H]taurocholate and ]14C]vinblastine, a P-glycoprotein (P-GP) substrate, intravenously administered as a bolus to bile-drained control rats or EHBR was studied. Biliary excretion of E217G and estradiol metabolites EHBR was markedly delayed. Analyses of biliary metabolites after estradiol injection showed less polar conjugates in EHBR. In contrast, the excretion of taurocholate and vinblastine (VLB) was only slightly delayed in EHBR. Although phenothiazine treatment to induce the expression of P-GP increased biliary vinblastine excretion, it did not affect biliary excretion of a tracer dose of [3H]estradiol-17beta-glucuronide. However, phenothiazine treatment inhibited the cholestasis induced by E217G infused at the rate of 0.075 micromol/min/100g for 20 minutes and increased biliary E217G excretion. Sulfobromophthalein infusion (0.2 micromol/min/100 g body 0 weight) markedly inhibited the biliary excretion of E217G and estradiol metabolites, whereas dibromosulfophthalein (DBSP) at the same infusion rate had no effect. These findings indicate that EG17G is excreted into bile by a canalicular organic anion carrier for sulfobromopthalein (BSP), not for DBSP, under physiological conditions, and that P-GP influences E217G excretion only at a high dose. under physiological conditions, and that P-GP influence s E217G excretion only at a high dose.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Effects of 17beta-estradiol on blood-brain barrier disruption during focal ischemia in rats.

This study was performed to test whether 17beta-estradiol could attenuate the blood-brain barrier disruption caused by middle cerebral artery occlusion in the ovariectomized rats. Rats aged twelve to fourteen weeks were used in this study. Their ovaries were removed one week prior to the implantation of the pellets. For the 17beta-estradiol group, a 500 microg 17beta-estradiol 21 day-release pellet was implanted and for the control group, a vehicle pellet was implanted 21 days before the experiments. One hour after middle cerebral artery occlusion under isoflurane anesthesia, the transfer coefficient of 14C-alpha-aminoisobutyric acid (104 Daltons) and the volume of 3H-dextran (70,000 Daltons) distribution were determined to represent the degree of blood-brain barrier disruption. Blood pressures and blood gases were similar between controls and 17beta-estradiol-treated rats. In both groups, the transfer coefficient of the ischemic cortex was higher than that of the corresponding contralateral cortex (control: Ischemic Cortex 12.5 +/- 5.9 microl/g/min, Contralateral Cortex 3.0 +/- 1.6, p < 0.001; 17beta-estradiol: Ischemic Cortex 6.7 +/- 3.3 micro l/g/min, Contralateral Cortex 2.2 +/- 0.9, p < 0.01). There was no significant difference in the transfer coefficient of the contralateral cortex between these two groups. However, the transfer coefficient of the Ischemic Cortex of the 17beta-estradiol-treated animals was 46 % lower than that of the control, vehicle-treated rats (p < 0.05). The increase of the volume of 3H-dextran distribution with middle cerebral artery occlusion was significant in the vehicle-treated rats (Ischemic Cortex: 6.4 +/- 2.7 ml/100 g, Contralateral Cortex: 3.8 +/- 0.8, p < 0.01) but not in the 17beta-estradiol-treated animals. Our data suggest that chronic 17beta-estradiol treatment was effective in reducing blood-brain barrier disruption during focal ischemia in the ovariectomized rats.

Aminoisobutyric Acids↗
PubMed2006

Effects of 17beta-estradiol on blood-brain barrier disruption during focal cerebral ischemia in younger and older rats.

This study was performed to compare the effects of 17beta-estradiol on blood-brain barrier disruption in focal cerebral ischemia between younger and older rats. Younger (three-month-old) and older (24-month-old) ovariectomized female Fischer 344 rats were studied. In one half of each age group, a 500 microg 17beta-estradiol 21-day release pellet and in another half, a vehicle pellet was implanted 21 days before the experiments. One hour after middle cerebral artery occlusion, the transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid and the volume of 3H-dextran distribution were determined to examine the degree of blood-brain barrier disruption. In all four groups, the Ki in the ischemic cortex was higher than in the corresponding contralateral cortex. There was no significant difference in the Ki in both cortices among the groups. The volume of dextran distribution of the ischemic cortex was only greater than in the corresponding contralateral cortex in the older 17beta-estradiol-treated group, and the volume of that group was greater than the younger 17beta-estradiol-treated group (4.00 +/- 1.29 VS. 2.13 +/- 0.88 ml/100 g). After analyzing the difference in Ki between the ischemic cortex and the contralateral cortex in each animal, the difference was significantly greater in the older 17beta-estradiol-treated rats than the older vehicle-treated rats (3.40 +/- 2.10 VS. 1.26 +/- 1.44 microl/g/min). In the younger rats, however, 17beta-estradiol did not significantly affect the difference. Our data showed that 17beta-estradiol treatment failed to attenuate the BBB disruption in the cerebral ischemic cortex in the older or younger Fischer 344 rats. However, our data also suggest the possibility that 17beta-estradiol could aggravate the BBB disruption in older rats.

Aging↗
PubMed1986

Biologic effects of transdermal estradiol.

We conducted a dose-response study in 23 postmenopausal women to compare the physiologic effects of transdermal estradiol and oral conjugated equine estrogens. The doses studied were 25, 50, 100, and 200 micrograms of transdermal estradiol per 24 hours, and 0.625 and 1.25 mg of oral conjugated estrogens. Transdermal estradiol increased circulating concentrations of estradiol and estrone. Oral conjugated estrogens also raised the levels of estrogen, particularly estrone. Both preparations lowered gonadotropin levels, decreased the percentages of vaginal parabasal cells, increased the percentage of superficial cells, and lowered urinary calcium excretion. The effects of 0.625 and 1.25 mg of oral estrogens were similar to those of 50 and 100 micrograms of transdermal estradiol per 24 hours, respectively. Oral estrogens significantly increased circulating levels of renin substrate, sex-hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin; transdermal estradiol had no effect. The higher dose of oral estrogens had favorable effects on concentrations of low-density and high-density lipoproteins, but transdermal estradiol did not. Neither preparation affected any of the four clotting factors studied. These data indicate that transdermal estradiol can elicit many of the desirable actions of estrogen while avoiding the pharmacologic effects of oral estrogens on hepatic proteins.

Administration, Oral↗