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PubMed1989

Estradiol or ovariectomy decreases CRF synthesis in hypothalamus.

Gonadectomy and gonadectomy plus chronic estradiol administration decrease the content of hypothalamic corticotropin-releasing factor-like immunoreactivity (CRF-ir). This investigation was conducted to determine whether this was a result of chronic inhibition of CRF synthesis or stimulation of release. Administration of the protein synthesis inhibitor anisomycin one hour prior to sacrifice in otherwise untreated controls resulted in a 21% decrease in median eminence CRF-ir (p less than 0.01). Rats were ovariectomized and then administered either estradiol or vehicle daily for 3 weeks. Compared to vehicle-treated controls, estradiol treatment decreased CRF-ir in median eminence (p less than 0.01). In contrast to controls, administration of anisomycin to these ovariectomized rats did not significantly decrease median eminence CRF-ir in either the vehicle or estradiol-treated groups, implying that CRF synthesis was already depressed. Plasma adrenocorticotropin (ACTH) was increased by anisomycin treatment in all groups whether intact, ovariectomized or estradiol-treated (p less than 0.0005). Adrenal weights did not differ between these groups, or in comparison to sham-ovariectomized rats, indirectly implying lack of chronically elevated plasma ACTH. These data suggest that the mechanism for both the ovariectomy and chronic estradiol-induced decrease in CRF-ir content is an inhibition of CRF synthesis as opposed to a stimulation of CRF release.

Adrenocorticotropic Hormone↗

PubMed1988

Effects of TCDD-estradiol interactions in three strains of mice.

Interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and estradiol were studied in three strains of mice: CD-1 and C57B/6 (TCDD sensitive) and DBA/2 (TCDD resistant at lower doses). Immature females were injected with 0-200 ng/kg/day estradiol for 2 weeks, s.c. On days 7, 9, 11, and 13, mice received 10 micrograms TCDD/kg by gavage. Relative uterine weight increased in mice of all three strains treated with estradiol alone. Uterine imbibition was suppressed by TCDD treatment, although this effect was antagonized in a saturable manner by coadministration of estradiol. TCDD induced aryl hydrocarbon hydroxylase (AHH) in liver microsomes of treated mice independent of estradiol dose and strain of mice (the dose of TCDD used was high enough to cause AHH induction in the resistant DBA/2 mice). Treatment of CD-1 mice, but not other strains, with TCDD and estradiol resulted in a decrease in the electrophoretic band of hepatic microsomal proteins comigrating with cytochrome P-450a and epoxide hydrase.

Age Factors↗

PubMed1994

Plasma concentrations of medroxyprogesterone acetate, estradiol and estrone following oral administration of Klimaxil, Trisequence/Provera and Divina. A randomized, single-blind, triple cross-over bioavailability study in menopausal women.

The absorption of estradiol and medroxyprogesterone acetate was investigated in a randomized single-blind, triple cross-over study, in 12 menopausal women, for four different HRT drugs (Klimaxil, a combination tablet containing 17 beta-estradiol 2 mg and medroxy-progesterone acetate 5 mg; Divina, a combination tablet containing 17 beta-estradiol valerate 2 mg and medroxyprogesterone acetate 10 mg; Trisequence, a triphasic preparation containing 17 beta-estradiol 2 mg in the first phase; Provera, a tablet containing medroxyprogesterone acetate 5 mg). Trisequence and Provera were ingested simultaneously. In conclusion, there was no statistically significant difference between the drugs with respect to the estradiol levels. The estrone concentration, however, differed between the different drugs. The serum concentration was higher after intake of tablets containing estradiol than after intake of tablets containing the valerate ester. There was a significant increase in the MPA levels between periods 1 and 3. Finally, Divina produced higher MPA concentrations than Klimaxil and the combination of Trisequence and Provera, although the mean AUC was not twice as high, as might have been expected.

Administration, Oral↗

PubMed1996

Serotonin metabolite excretion after postmenopausal estradiol therapy.

Serotonin, known for its beneficial action on mood and well-being, is also involved in cardiovascular functions. Thus the current work was undertaken to study the effect of hormone replacement therapy on serotonin turnover in postmenopausal women. Eighteen women received estradiol transdermally and 17 women estradiol valerate orally for 4 weeks. The serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) was determined in the urine before, and after 2 and 4 weeks' estradiol treatment. With both administration routes estradiol produced a significant increase in urinary 5-HIAA excretion, greatest with transdermal estradiol after 28 days of treatment. The enhancement of serotonin turnover may contribute not only to an improvement of mood and well-being but also to a cardioprotective effect of estradiol observed after hormone substitution in postmenopausal women.

Administration, Cutaneous↗

PubMed1996

Depressed luteinizing hormone response to estradiol in vivo and gonadotropin-releasing hormone in vitro in experimentally diabetic swine.

The influence of the acute withdrawal of insulin therapy in streptozocin-diabetic female swine was examined for changes in 1) the in vivo pulsatile secretion of luteinizing hormone (LH), 2) the preovulatory-like gonadotropin patterns after exogenous estradiol, and 3) the in vitro LH secretion by cultured pituitary cells. In Experiment 1, ovariectomized diabetic pigs (n = 4) were maintained with insulin therapy until 4 d before estradiol benzoate (EB; 7 micrograms/kg body weight; subcutaneous) was administered. Four normal ovariectomized pigs, matched for age and weight, served as controls. The diabetic state was confirmed by the measurement of glucose and insulin concentrations during a glucose tolerance test. Pulsatile LH secretion was not influenced by experimental diabetes mellitus. However, the expected surge in LH was not induced by EB in diabetic gilts. In contrast, three of four normal gilts had a preovulatory-type surge in LH. Concentrations of follicle-stimulating hormone in serum were not affected by diabetes mellitus. Estradiol concentrations in serum after ER were influenced by diabetes mellitus (treatment by time interaction; P < 0.001). In individual estradiol profiles, maximum concentrations were similar (104 +/- 10.4 and 91 +/- 12.0 ng/ml for normal and diabetic pigs, respectively), but the interval to maximum concentration was delayed in diabetic pigs (27.5 vs. 9.0 h; SE = 3.0; P < 0.05). However, the duration of standing estrus (2.2 +/- .3 d) and the interval from EB to estrus (3.6 +/- 0.3 d) were not influenced by diabetes mellitus. In Experiment 2, LH secretion by cultured cells and residual cellular LH content were greater in the pituitaries of normal than diabetic pigs (P < 0.05), and only cells from normal pigs responded to gonadotropin-releasing hormone (GnRH), with increased production of LH (P < 0.05). In conclusion, diabetes mellitus did not affect pulsatile LH secretion but did lower the ability of exogenous estradiol to stimulate a surge in vivo and of GnRH to increase LH in vitro, suggesting that the pituitary response to estradiol and GnRH is more severely affected by diabetes than is the GnRH pulse generator.

Animals↗

PubMed1991

Enzyme immunoassay for plasma estradiol using a monoclonal antibody.

A microtitre plate enzyme immunoassay (EIA) for plasma estradiol is described, involving competition between sample estradiol and an immobilized estradiol-bovine serum albumin complex for a monoclonal anti-estradiol antibody, followed by immobilized antibody quantitation using enzyme-labelled antiglobulins. The assay dose-response curve covered a range of 6-1500 fmol/well. The intra- and inter-assay coefficient of variation for the assay of three plasma pools ranged from 3.1 to 4.7% and from 4.7 to 10.6% respectively. The assay showed satisfactory correlation with a standard estradiol radioimmunoassay. Pre-coated microtitre plates were stable, dried, at 4 degrees C for up to 3 months and the anti-estradiol was stable to lyophilization and also was stable in solution at 4 degrees C for up to 1 month.

Antibodies, Monoclonal↗

PubMed1993

Generation of estradiol within the pregnant guinea pig uterine compartment with special reference to the myometrium.

Between about 50 and 58 days of gestation, the guinea pig chorion becomes attached in its entirety to the uterine wall, suggesting a facilitation of transfer of agents such as steroids between these tissues. At a time between 59 and 64 days, relaxation of the pubic symphysis starts, and anywhere from 5 to 8 days after that event delivery takes place. The present in vitro study was undertaken to evaluate estrone sulfate as a substrate for local production of estradiol, via the action of estrogen sulfatase and 17-hydroxysteroid dehydrogenase, in chorion, endometrium and myometrium taken at four distinct stages of gestation, as follows: 50 days, representing pre-chorion attachment to the uterus (stage 50); 1 or 2 days before pubic symphysis relaxation (minus 1 day, or -1 day); 1 day following relaxation (+1 day); and 1-2 days before delivery (late, or L). At these same stages, the metabolite patterns formed from estradiol were evaluated for endometrium and myometrium. Each of the tissues behaved somewhat differently. Overall hydrolysis of estrone sulfate by endometrium and myometrium exceeded that by chorion. Generation of free steroid from estrone sulfate increased 3-fold in chorion between stages 50 and -1 and during this period estradiol production from estrone sulfate increased 9-fold and continued to rise until delivery. Cytosolic estrogen sulfotransferase activity of chorion decreased 7-fold between stages 50 and -1. This suggested a tissue environment geared to producing potentially active estradiol. However, myometrium converted very little estrone into estradiol until just before delivery despite the facile formation of estrone from estradiol at stages -1, +1 and L. The control of estrogen metabolism by interaction of tissues in the uterus and by some form of enzyme regulation in these tissues suggests a possible role for locally produced estrogen in the stages leading up to parturition.

17-Hydroxysteroid Dehydrogenases↗

PubMed1995

Estradiol and testosterone in specific regions of the human female brain in different endocrine states.

Post-mortem concentrations of estradiol and testosterone were measured in 17 brain areas, serum and fat in 6 fertile and 5 postmenopausal women. Steroid concentrations were measured with radioimmunoassay after extraction of brain tissue with ethanol and purification with celite chromatography. There were regional differences in brain concentrations of both steroids. The highest levels of estradiol and testosterone were noted in the hypothalamus, preoptic area and substantia nigra. These findings may assist in the interpretation of functional animal studies where the hypothalamus-preoptic area and the nigrostriatal dopamine system have proved to be target areas for estradiol. When compared to postmenopausal women, estradiol concentrations were significantly higher in the brains of fertile women, which indicates that peripheral serum levels of estradiol are reflected in the brain. This study has yielded information about steroid levels in different endocrine states and could provide a frame of reference for studies of estradiol and testosterone mediated effects on the central nervous system.

Adipose Tissue↗

PubMedDate not supplied

Micronized estradiol and progesterone: effects on carbohydrate metabolism in reproductive-age women.

OBJECTIVE: We assessed glucose utilization and insulin sensitivity in normal reproductive-age women after administration of micronized estradiol, micronized progesterone, or the combination of micronized estradiol and progesterone. METHODS: Hyperglycemic and euglycemic, hyperinsulinemic clamp studies were performed in normal, regularly cycling women both before and after a short course of either micronized estradiol (n = 8), micronized progesterone (n = 8), or micronized estradiol and progesterone (n = 7). All studies were performed after an overnight fast. Glucose and insulin were determined in the control period and then every 2-10 minutes in the hyperglycemic clamp studies and every 5-10 minutes in the euglycemic clamp studies. In the hyperglycemic clamp studies, hyperglycemia was maintained by a variable glucose infusion. In the euglycemic clamp studies, a primed 3-3H glucose infusion (25 microCi) followed by a 0.25-microCi continuous infusion was begun 120 minutes before initiation of the insulin infusion and variable glucose infusion. Samples for glucose radioactivity were measured during the control period and during the last 40 minutes of each step of the euglycemic clamp after establishment of a steady state. RESULTS: No differences in baseline glucose or insulin levels were detected in any of the study groups as compared with control. Glucose utilization as assessed by the hyperglycemic clamp model was not significantly different from control in the estradiol group, the progesterone group, or the group treated with the combination. In all of the treatment groups, no significant differences were noted under euglycemic, hyperinsulinemic conditions in glucose utilization, hepatic glucose production, or insulin sensitivity. CONCLUSIONS: Women of reproductive age do not demonstrate significant differences in basal levels of glucose or insulin when given a short course of micronized estradiol and progesterone, either alone or in combination. Under conditions of the hyperglycemic, hyperinsulinemic clamp, the pancreatic beta-cell response to hyperglycemia and glucose utilization is not significantly altered by exogenous administration of hormones. Conditions of the euglycemic, hyperinsulinemic clamp failed to elicit significant differences in glucose utilization and insulin sensitivity in any of the three treatment groups. These findings demonstrate that glucose homeostasis is not altered by the exogenous administration of natural hormones in reproductive-age women.

Adult↗

PubMed1991

Preservation of ectopically induced bone in the mouse by estradiol.

The effects of estrogen on bone formation and bone resorption were examined in an experimental model of ectopic bone induction. In this experimental model, ectopic ossicles of uniform size were elicited reproducibly in three weeks by implanting pellets containing murine osteosarcoma derived bone morphogenetic protein (BMP), into the muscles of mice. Thereafter the induced ossicles showed a gradual reduction in bone mass due to negative bone balance. To estimate the effects of estrogen on bone formation and bone resorption, beta-estradiol-3-benzoate was administered exogenously to host mice from day 21 to day 41 (0.45 micrograms/g body weight, on alternate days, 10 treatments). Radiologic and histologic analysis confirmed the positive effect of estradiol on preserving bone mass over this period. Quantitative analysis showed an increase in the Ca content in ossicles after 21 days of estradiol treatment (139.1% of the baseline value on day 21). In the control group, the bone mass was reduced (47.4% of that on day 21). Bone resorption was determined by the reduction in 45Ca radioactivity from ossicles prelabeled with this radioisotope before estradiol administration. The rate of loss of the prelabeled 45Ca radioactivity was suppressed by estradiol (68.8% of prelabeled value in estradiol treated group and 87.7% in control group). The effect of exogenous estrogen on the bone forming phase of bone turnover in the ossicles was quantified by incorporation of 45Ca and 3H-proline. These bone formation parameters were increased to 2.2 and 1.9 times higher than those of the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2005

Effects of 17beta-estradiol exposure in the mussel Mytilus galloprovincialis: a possible regulating role for steroid acyltransferases.

Mussels (Mytilus galloaprovincialis) were exposed to different concentrations of estradiol (20, 200, and 2000 ng/L) in a semi-static regime (1-day dosing intervals) for up to 7 days in an attempt to see how mussels deal with exogenous estrogenic compounds. Whole tissue free-estradiol levels were only significantly elevated at the high exposure dose, whereas total-estradiol (free+esterified) sharply increased in a dose-dependent manner, from 2 ng/g in controls to 258 ng/g at the high exposure group. Neither free nor esterified testosterone levels showed significant differences between control and exposed organisms. The results suggest the existence of mechanisms that allow mussels to maintain their hormonal levels stable, with the exception of the high exposure dose, and the important role that fatty acid esterification, e.g. palmitoyl-CoA:estradiol acyltransferases, may play within those mechanisms. Additionally, the activity of 17beta-hydroxysteroid dehydrogenase (17beta-HSD), 5alpha-reductase, P450-aromatase, and estradiol-sulfotransferases were investigated in digestive gland microsomal and cytosolic fractions. All these activities were differently affected by estradiol exposure. Overall, the study contributes to the better knowledge of molluscan endocrinology, and defines new mechanisms of regulation of free steroid-levels in mussels.

Acyltransferases↗

PubMed2006

Laboratory exposure to 17beta-estradiol fails to induce vitellogenin and estrogen receptor gene expression in the marine invertebrate Mytilus edulis.

To investigate the effect of estrogenic compounds on the marine mussel Mytilus edulis, an assay was developed to measure the expression of two vertebrate estrogen responsive genes-estrogen receptor (ER) and vitellogenin (VTG) genes. Expression was measured in M. edulis gonads following a 10-day exposure to 200 ng/l 17beta-estradiol (estradiol). The concentrations of esterified estradiol in mussel tissue increased 15-fold in a time-dependent manner-confirming uptake of the compound by the mussels, however there was no significant increase of free estradiol in mussel tissues during the exposure period. The ER and VTG mRNA levels in the gonads of both sexes were measured at days 1-3, 5, and 10 in control and exposed mussels. However, no significant change in the expression of either the ER or VTG genes was recorded at any of the sampled time points. The results suggest that either a regulatory mechanism exists in a mussel that is able to maintain constant levels of free estradiol by converting the excess estradiol into esterified products which may have reduced affinity for the estrogen receptor, or alternatively, that the ER and VTG genes are unresponsive to estrogens in these organisms. The significance of these findings in terms of the utility of ER and VTG as biomarkers of endocrine disruption in bivalve species is discussed.

Amino Acid Sequence↗

PubMed2004

17beta-Estradiol nitration by peroxidase/H2O2/NO2-: a chemical assessment.

Nitration of 17beta-estradiol by H(2)O(2) and nitrite in the presence of various peroxidases, viz. horseradish peroxidase, lactoperoxidase, and peroxidase-containing homogenates from bovine uteri, was systematically investigated to assess on a chemical basis its potential relevance to the mechanisms of impairment of estrogen functions under oxidative/nitrosative stress conditions. In the presence of excess nitrite 17beta-estradiol reacted smoothly to give 2-nitroestradiol (1), 4-nitroestradiol (2), and 2,4-dinitroestradiol (3). With 10-300 microM estradiol, formation yields of 1-3 were 12-55%, but dropped to 1% or less at lower estrogen concentration, for example, 1 microM, or in plasma as the reaction medium. Time course analysis showed that 2 is the prevalent nitration product under conditions of slow generation of nitrating species, suggesting some regioselectivity for estradiol nitration at C-4, whereas 1 prevails with bolus addition of reagents, due to faster degradation of 2. Competition experiments carried out with (15)NO(2)- showed that 2 is about twice more susceptible to nitration than 1 as determined by (15)N NMR analysis of the resulting 3. The biological effects of 1 and 2 were preliminarily tested on in vitro bovine embryo cultures. When 1 and 2 were substituted to the standard 17beta-estradiol in the oocyte maturation, a significant decrease in both cleavage and blastocyst efficiency was observed in the case of 1 but not 2. Overall, these results suggest that estradiol nitration is a potential pathway of hormonal dysfunction and toxicity but would require elevated estrogen levels of questionable physiological relevance.

Animals↗

PubMed2006

Influence of 17beta-estradiol and insulin on type II collagen and protein synthesis of articular chondrocytes.

Clinical observations have suggested a relationship between osteoarthritis and a changed estrogen metabolism in menopausal women. Type II collagen is one main structural protein of articular cartilage matrix and its synthesis is increased by insulin in growth plate cartilage. Therefore, it was investigated if [(3)H]-proline incorporation and type II collagen synthesis (immunocytochemistry, ELISA) in female bovine articular chondrocytes are affected by 17beta-estradiol and/or insulin. Articular chondrocytes were cultured in monolayers at 5% O(2) in medium containing serum for 5-9 days, followed by application of 10(-13) to 10(-9) M estradiol or 5 microg/ml insulin during a serum-free culture phase of 2-3 days. Immunostaining for type II collagen was strong in the serum-free culture phase whereas it was negative for type I collagen, indicating that cells did not dedifferentiate to fibroblast-like cells during culture in serum-free medium. Whereas insulin raised the proline incorporation and the type II collagen synthesis significantly, physiological doses of estradiol did not show significant effects. The stimulating effect of insulin on the [(3)H]-proline incorporation or the type II collagen synthesis was significantly suppressed after preincubation of cells with 10(-11) to 10(-9) M estradiol resembling an unfavorable effect for articular cartilage. The suppression was reversed if cells were incubated with 10(-11) to 10(-7) M tamoxifen or ICI 182,780 combined with 10(-11) or 10(-9) M estradiol followed by incubation with 5 microg/ml insulin, indicating an estrogen receptor-mediated process. Because the articular cartilage of diabetic patients is biomechanically less stable, further experiments are needed to clarify the role of estradiol and insulin in the metabolism of articular chondrocytes.

Animals↗

PubMed2005

Zinc and 17beta-estradiol induce modifications in Na+/H+ exchanger and pyruvate kinase activity through protein kinase C in isolated mantle/gonad cells of Mytilus galloprovincialis.

We investigated the transduction pathway mediated by Zn and 17beta-estradiol in isolated mantle/gonad cells of the mussel Mytilus galloprovincialis. Both the essential metal Zn, and the estrogen 17beta-estradiol, caused an increase in intracellular pH (pHi) of isolated mantle/gonad cells of the mussel M. galloprovincialis, thus indicating the activation of the Na+/H+ exchanger (NHE). The observed effect was inhibited by EIPA (20 nM), a specific NHE inhibitor, thus verifying NHE activation. Protein kinase C (PKC) also seemed to play an activating role in zinc and 17beta-estradiol effects on NHE and PK activity. In addition, the glycolytic enzyme pyruvate kinase (PK) was increased after zinc, while it was decreased after 17beta-estradiol treatment. It is noteworthy that, both the latter effects were reversed in the presence of EIPA, indicating the involvement of NHE in the signaling mechanism. cAMP seems to participate in the signaling mechanism induced by Zn but not to that induced by 17beta-estradiol. The potential implication of the heavy metal and 17beta-estradiol on the reproductive activity of the marine animals is discussed.

Amiloride↗

PubMed2004

Effects of estradiol administration on feto-placental growth in rat.

BACKGROUND: To clarify the effect of estradiol benzoate on placental structure and its consequences for fetal survival and fetoplacental growth. STUDY DESIGN: Estradiol benzoate (0, 0.1, 1, 10, 100 microg/day) was infused intraperitoneally into pregnant Wistar rats from 12 to 19 days' gestation. Survival rate, weight of pups and placentas at 20 days' gestation, and plasma levels of estrogen and progesterone were measured. Pathological changes in the placenta were also examined. RESULTS: Estradiol benzoate reduced fetal survival (1 microg/day: 100%, 10 microg/day: 70%, 100 microg/day: 14.6%) and the weights of the pups and placentas in a dose-dependent manner. Maternal estradiol concentration was raised 23-fold with 100microg/day of estradiol benzoate. Trophoblast degeneration, including apoptosis and destruction of placental labyrinth was induced but the structures of the maternal kidney and liver were not affected. CONCLUSIONS: In pregnant rats, estradiol benzoate causes fetal mortality at a pharmacological dose (more than 10 microg/day) and fetoplacental growth retardation via trophoblastic degeneration and destruction of the placental labyrinth even at a physiological dose (1 microg/day).

Animals↗

PubMed2004

Uptake of estradiol or progesterone into the CSF following intranasal and intravenous delivery in rats.

The uptake of estradiol and progesterone into the cerebrospinal fluid (CSF) after intranasal and intravenous administration in rats was investigated. Each animal received estradiol intranasally (40 microg/rat) and by intravenous infusion (10 microg/rat) into the jugular vein using a vascular access port. Hereafter, the same set of rats was treated with progesterone intranasally (200 microg/rat) and by intravenous infusion (104 microg/rat). Following nasal delivery, both steroid hormones reach Cmax values in plasma and CSF at 15 min after administration. Intravenous infusion of estradiol and progesterone shows comparable plasma and CSF concentration-time profiles compared to the nasal route. For both hormones the AUCCSF/AUCplasma ratios (mean +/- SD) after intranasal delivery (estradiol 2.3 +/- 1.1%; progesterone 1.9 +/- 0.7%) do not differ significantly from the ratios shown after intravenous infusion (estradiol 2.0 +/- 0.6%; progesterone 2.2 +/- 0.8%). These results indicate that after nasal delivery estradiol and progesterone are rapidly absorbed into the systemic circulation, from where the non-protein bound hormones probably enter the CSF by crossing the blood-brain barrier. No extra direct nose-CSF transport could be demonstrated.

Administration, Intranasal↗

PubMed2006

Estradiol regulation of astroglia and apolipoprotein E: an important role in neuronal regeneration.

The effects of ovarian hormone on neuronal growth and function are well known. However, equally important, but often neglected, are ovarian hormone effects on glia. Our in vivo and in vitro studies show that estradiol modifies both neuronal growth and glial activity and these effects are tightly linked. Estradiol stimulates neurite growth and the release of the glial apolipoprotein E (apoE) in culture studies. Estradiol-stimulated neurite growth in these cultures requires apoE. Estradiol replacement in ovariectomized mice transiently increases the expression of apoE, the low density lipoprotein receptor related protein (LRP) and synaptophysin throughout the brain. Continuous estradiol replacement over two months loses effect on apoE, LRP, and synaptophysin and suppresses reactive gliosis. Estrous cycle variation of glial activation (GFAP) and apoE are not identical. We propose that estradiol (and other ovarian hormones) functions as a zeitgeber to co-ordinate neuronal-glial interactions. Co-ordination assures temporally appropriate excitatory and inhibitory interactions between glia and neurons. With aging and the loss of ovarian cyclicity, some of this co-ordination must be diminished. These observations present significant clinical implications. Approaches to hormone therapy (HT), for diminishing the risk of chronic neurological diseases, need to consider the temporal nature of ovarian hormones in brain repair and plasticity. Moreover, approaches must consider apoE genotype. The neuroprotective effects of HT in numerous chronic age-related diseases may represent effective co-ordination of repair processes rather than direct disease-specific actions. Moreover, the role of glial-derived proteins in neuroprotection should not be ignored.

Adult↗