Distributions of PCB congeners and homologues in white sucker and coho salmon from Lake Michigan

USGS Publications Warehouse

Stapanian, Martin A.; Madenjian, Charles P.; Batterman, Stuart A.; Chernyak, Sergei M.; Edwards, William H.; McIntyre, Peter B.

2018-01-01

We tested the hypothesis of the proportion of higher chlorinated biphenyl (PCB) congeners increasing with increasing trophic level by comparing the respective PCB homologue distributions in an omnivore, white sucker (Catostomus commersoni), and a top predator, coho salmon (Oncorhynchus kisutch), from Lake Michigan. Adult females had the same congener and homologue proportions of total PCB concentration (ΣPCB) as adult males in both species. Hexachlorinated congeners comprised the largest proportion (32%) found in white sucker, followed by heptachlorinated (21%) and octochlorinated (18%) congeners. In contrast, pentachlorinated congeners comprised the largest proportion (33%) of ΣPCB found in coho salmon, followed by hexachlorinated (26%) and tetrachlorinated (24%) congeners. Coho salmon contained significantly higher proportions of tri-, tetra-, and pentachlorinated congeners, whereas white sucker contained significantly higher proportions of hexa- through decachlorinated congeners. Our results were opposite of the hypothesis of greater degree of PCB chlorination with increasing trophic level, and supported the contention that the PCB congener proportions in fish depends mainly on diet, and does not necessarily reflect the trophic level of the fish. Our results also supported the contention that diets do not vary between the sexes in most fish populations.

40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

Code of Federal Regulations, 2014 CFR

2014-07-01

... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only congeners...

40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

Code of Federal Regulations, 2011 CFR

2011-07-01

... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only congeners...

40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

Code of Federal Regulations, 2013 CFR

2013-07-01

... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only congeners...

40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

Code of Federal Regulations, 2012 CFR

2012-07-01

... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only congeners...

40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

Code of Federal Regulations, 2010 CFR

2010-07-01

... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only congeners...

Evidence of latitudinal fractionation of polychlorinated biphenyl congeners along the Baltic Sea region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agrell, C.; Okla, L.; Larsson, P.

Annual cycles of the atmospheric concentrations of PCBs were determined at 16 (mostly rural) stations around the Baltic Sea between 1990 and 1993. The concentration levels of individual congeners were found to be influenced by their physical-chemical properties, ambient temperature, and geographical location. Median levels of PCBs were similar at all stations except at one urban site near Riga. A latitudinal gradient with higher levels in the south was found for the sum of PCB as well as for individual congeners, and the gradient was more pronounced for the low volatility congeners. As a result, the high volatility congeners increasedmore » in relative importance with latitude. Generally, PCB concentrations increased with temperature, but slopes of the partial pressure in air versus reciprocal temperature were different between congeners and between stations. In general, the low volatility congeners were more temperature dependent than the high volatility PCB congeners. Steep slopes at a sampling location indicate that the concentration in air is largely determined by diffusive exchange with soils. Lack of a temperature dependence may be due to the influence of long-range transported air masses at remote sites and due to the episodic or random nature of PCB sources at urban sites.« less

Congener specific biotransformation and bioaccumulation of PCDDs and PCDFs from fly ash in fish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sijm, D.T.H.M.; Opperhuizen, A.; Wever, H.

1993-10-01

Biotransformation may be responsible for the lack of bioaccumulation of a number of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). Goldfish (Carassius auratus) that were exposed to PCDDs and PCDFs, and piperonylbutoxide (PBO) in water bioconcentrated significantly more congeners than goldfish exposed to PCDDs and PCDFs only. Monooxygenase activity, which is responsible for the oxidation of specific PCDD and PCDF congeners in untreated fish, was inhibited by fish treated with PBO. In the PBO-treated group and in the control group, congeners with all lateral positions substituted were found. Congeners that lack chlorine substitution on one or more of the lateral positionsmore » substituted were found. Congeners that lack chlorine substitution on one or more of the lateral (2,3,7,8) positions and congeners that have all lateral positions chlorinated were found only in PBO-treated fish. Congeners that have at least one free lateral position were therefore assumed to be biotransformed. There was no relationship between the octanol/water partition coefficient and biotransformed. There was no relationship between the octanol/water partition coefficient and biotransformation of the PCDDs and PCDFs. No limitation of uptake for higher chlorinated PCDD and PCDF congeners was found.« less

Serum PCB levels and congener profiles among teachers in PCB-containing schools: a pilot study

PubMed Central

2011-01-01

Background PCB contamination in the built environment may result from the release of PCBs from building materials. The significance of this contamination as a pathway of human exposure is not well-characterized, however. This research compared the serum PCB concentrations, and congener profiles between 18 teachers in PCB-containing schools and referent populations. Methods Blood samples from 18 teachers in PCB-containing schools were analyzed for 57 PCB congeners. Serum PCB concentrations and congener patterns were compared between the teachers, to the 2003-4 NHANES (National Health and Nutrition Examination Survey) data, and to data from 358 Greater Boston area men. Results Teachers at one school had higher levels of lighter (PCB 6-74) congeners compared to teachers from other schools. PCB congener 47 contributed substantially to these elevated levels. Older teachers (ages 50-64) from all schools had higher total (sum of 33 congeners) serum PCB concentrations than age-comparable NHANES reference values. Comparing the teachers to the referent population of men from the Greater Boston area (all under age 51), no difference in total serum PCB levels was observed between the referents and teachers up to 50 years age. However, the teachers had significantly elevated serum concentrations of lighter congeners (PCB 6-74). This difference was confirmed by comparing the congener-specific ratios between groups, and principal component analysis showed that the relative contribution of lighter congeners differed between the teachers and the referents. Conclusions These findings suggest that the teachers in the PCB-containing buildings had higher serum levels of lighter PCB congeners (PCB 6-74) than the referent populations. Examination of the patterns, as well as concentrations of individual PCB congeners in serum is essential to investigating the contributions from potential environmental sources of PCB exposure. PMID:21668970

The Binding Constant of Estradiol to Bovine Serum Albumin: An Upper-Level Experiment Utilizing Tritium-Labeled Estradiol and Liquid Scintillation Counting

ERIC Educational Resources Information Center

Peihong Liang; Adhyaru, Bhavin; Pearson, Wright L.; Williams, Kathryn R.

2006-01-01

The experiment used [to the third power]H-labeled estradiol to determine the binding constant of estradiol to bovine serum albumin. Estradiol must complex with serum proteins for the transport in the blood stream because of its low solubility in aqueous systems and estradiol-protein binding constant, where K[subscript B] is important to understand…

DIBROMOACETIC ACID-INDUCED ELEVATIONS OF ESTRADIOL IN THE CYCLING AND OVARIECTOMOZED/ESTRADIOL-IMPLANTED FEMALE RAT

EPA Science Inventory

Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations of Estradiol in Both Cycling and Ovariectomized / Estradiol-implanted Female Rats

ABSTRACT
Haloacetic acids are one of the principal classes of disinfection by-products generated by the chlorination of mun...

ELECTRONIC ELASTICITY-TOXICITY RELATIONSHIPS FOR POLYCHLORINATED DIBENZO-P-DIOXIN CONGENERS. (R826166)

EPA Science Inventory

SCF-MO computations have been performed on tetra- to octa-chlorinated dibenzo-p-dioxin congeners (PCDD) using an MNDO-PM3 Hamiltonian. Qualitative relationships were developed between empirical, international-toxic equivalence factors for PCDD congeners and their relati...

77 FR 31722 - New Animal Drugs; Change of Sponsor; Estradiol; Estradiol Benzoate and Testosterone Propionate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-30

... 558 [Docket No. FDA-2012-N-0002] New Animal Drugs; Change of Sponsor; Estradiol; Estradiol Benzoate.... ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect a change of sponsor for 17 new animal drug applications (NADAs) and abbreviated new...

Incubation stage and polychlorinated biphenyl (PCB) congener patterns in an altricial and precocial bird species

USGS Publications Warehouse

Custer, Christine M.; Custer, Thomas W.; Thyen, Stefan; Becker, Peter H.

2014-01-01

The composition of polychlorinated biphenyl (PCB) congeners was compared between non-incubated and embryonated eggs of tree swallows (Tachycineta bicolor) and little terns (Sterna albifrons) to determine if measurable changes in PCB congeners occurred during the embryonic period. There was no indication of changes in PCB congener patterns over the incubation period in tree swallows in 1999 and 2000 at a site with very high PCB exposure or a site with more modest PCB exposure. Additionally, congeners known to be either quickly metabolized or conserved based on experimental studies did not generally respond as predicted. Similarly, PCB congener patterns in eggs of little terns from Bottsand, Schleswig-Holstein, Germany, did not differ between non-incubated and embryonated eggs. The results from both species suggest that the stage of incubation is not an important consideration when evaluating PCB congener patterns; comparisons and assessments can be made with eggs collected at all stages of incubation.

Incubation stage and polychlorinated biphenyl (PCB) congener patterns in an altricial and precocial bird species.

PubMed

Custer, Christine M; Custer, Thomas W; Thyen, Stefan; Becker, Peter H

2014-12-01

The composition of polychlorinated biphenyl (PCB) congeners was compared between non-incubated and embryonated eggs of tree swallows (Tachycineta bicolor) and little terns (Sterna albifrons) to determine if measurable changes in PCB congeners occurred during the embryonic period. There was no indication of changes in PCB congener patterns over the incubation period in tree swallows in 1999 and 2000 at a site with very high PCB exposure or a site with more modest PCB exposure. Additionally, congeners known to be either quickly metabolized or conserved based on experimental studies did not generally respond as predicted. Similarly, PCB congener patterns in eggs of little terns from Bottsand, Schleswig-Holstein, Germany, did not differ between non-incubated and embryonated eggs. The results from both species suggest that the stage of incubation is not an important consideration when evaluating PCB congener patterns; comparisons and assessments can be made with eggs collected at all stages of incubation. Published by Elsevier Ltd.

Hemostatic effects of a novel estradiol-based oral contraceptive: an open-label, randomized, crossover study of estradiol valerate/dienogest versus ethinylestradiol/levonorgestrel.

PubMed

Klipping, Christine; Duijkers, Ingrid; Parke, Susanne; Mellinger, Uwe; Serrani, Marco; Junge, Wolfgang

2011-01-01

A novel estradiol-based combined oral contraceptive (COC) is currently available in many countries worldwide, including Europe and the US. Based on previous studies, it is expected that this estradiol-based COC will have a reduced hepatic effect compared with COCs containing ethinylestradiol with regard to proteins controlling the hemostatic balance. The aim of this study was to compare the hemostatic effects of the estradiol valerate/dienogest COC with a monophasic low-estrogen dose COC containing ethinylestradiol/levonorgestrel. Healthy women aged 18-50 years were randomized to receive a COC containing estradiol valerate/dienogest (2 days estradiol valerate 3 mg, 5 days estradiol valerate 2 mg/dienogest 2 mg, 17 days estradiol valerate 2 mg/dienogest 3 mg, 2 days estradiol valerate 1 mg, 2 days placebo) or ethinylestradiol 0.03 mg/levonorgestrel 0.15 mg in a crossover study design. Women received each treatment for three cycles, with two washout cycles between treatments. The primary efficacy variables were the intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three. Data from 29 women were assessed. Intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three were less pronounced with estradiol valerate/dienogest than with ethinylestradiol/levonorgestrel. The novel COC containing estradiol valerate/dienogest had similar or less pronounced effects on hemostatic parameters than ethinylestradiol/levonorgestrel.

Congener-specific polychlorinated biphenyl patterns in eggs of aquatic birds from the lower Laguna Madre, Texas

USGS Publications Warehouse

Mora, Miguel A.

1996-01-01

Eggs from four aquatic bird species nesting in the Lower Laguna Madre, Texas, were collected to determine differences and similarities in the accumulation of congener-specific polychlorinated biphenyls (PCBs) and to evaluate PCB impacts on reproduction. Because of the different toxicities of PCB congeners, it is important to know which congeners contribute most to total PCBs. The predominant PCB congeners were 153, 138, 180, 110, 118, 187, and 92. Collectively, congeners 153, 138, and 180 accounted for 26 to 42% of total PCBs. Congener 153 was the most abundant in Caspian terns (Sterna caspia) and great blue herons (Ardea herodias) and congener 138 was the most abundant in snowy egrets (Egretta thula) and tricolored herons (Egretta tricolor). Principal component analysis indicated a predominance of higher chlorinated biphenyls in Caspian terns and great blue herons and lower chlorinated biphenyls in tricolored herons. Snowy egrets had a predominance of pentachlorobiphenyls. These results suggest that there are differences in PCB congener patterns in closely related species and that these differences are more likely associated with the species' diet rather than metabolism. Total PCBs were significantly greater (p < 0.05) in Caspian terns than in the other species. Overall, PCBs in eggs of birds from the Lower Laguna Madre were below concentrations known to affect bird reproduction.

Drospirenone/ethinyl estradiol.

PubMed

Rapkin, Andrea J; Sorger, Shelley N; Winer, Sharon A

2008-02-01

Drospirenone 3 mg/ethinyl estradiol 20 microg (24/4) is a new unique oral contraceptive formulation that combines in a novel dosing regimen the lowest dosage of ethinyl estradiol commonly used today with drospirenone, an innovative progestin. Drospirenone is a compound closely resembling progesterone, but with the antimineralocorticoid and antiandrogenic properties of a related therapeutic agent, the diuretic, antihypertensive and androgen receptor antagonist, 17alpha-spironolactone. The prolongation of hormonally active pills in the monthly drospirenone/ethinyl estradiol cycle from 21 days to 24 days, followed by 4 days of inactive pills, is an interesting variant of the recently developed extended pill regimens (1). Recent contraceptive research has focused on improving side effect profiles and providing noncontraceptive health and lifestyle advantages. Many of these benefits are now supported with evidence-based medicine (2). Most available oral contraceptives improve cycle regularity, menstrual pain, excessive menstrual flow and acne. However, weight gain, bloating, food cravings, breast tenderness and mood alterations (especially irritability and depression and the complex of affective, behavioral and somatic symptoms of premenstrual syndrome [PMS] and the severe form of PMS, premenstrual dysphoric disorder [PMDD]) are not generally improved with the traditional oral contraceptive formulations (3). Drospirenone/ethinyl estradiol 24/4 is currently the only hormonally based contraceptive regimen with large, randomized, controlled trials demonstrating efficacy for PMDD. It has received U.S. Food and Drug Administration (FDA) indications not only for the prevention of pregnancy but also for PMDD and for moderate acne vulgaris in women who choose oral contraception for birth control (4, 5). Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

Polychlorinated biphenyl congener patterns in fish near the Hanford Site (Washington State, USA).

PubMed

Rodenburg, Lisa A; Delistraty, Damon; Meng, Qingyu

2015-03-03

It is well-known that absorption, distribution, metabolism, and excretion (ADME) processes in fish can alter polychlorinated biphenyl (PCB) congener patterns in fish, but these patterns have never been investigated using an advanced source-apportionment tool. In this work, PCB congener patterns in freshwater fish were examined with positive matrix factorization (PMF). PCB congeners were quantified via EPA Method 1668 in fillet and carcass of six species in four study areas in the Columbia River near the Hanford Site. Six factors were resolved with PMF2 software. Depletion and enhancement of PCB congeners in factors, relative to Aroclor 1254, suggested biotransformation (via cytochrome P450) and bioaccumulation in fish, respectively. Notable differences were observed among species and across study locations. For example, sturgeon and whitefish exhibited congener patterns consistent with Aroclor weathering, suggesting potential PCB metabolism in these species. In terms of location, average concentration of total PCBs for all species combined was significantly higher (P < 0.05) at Hanford 100 and 300 areas, relative to upriver and downriver study sites. Furthermore, a distinct PCB signature in sturgeon and whitefish, collected at Hanford study areas, suggests that Hanford is a unique PCB source.

21 CFR 556.240 - Estradiol and related esters.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol... increments above the concentrations of estradiol naturally present in untreated animals: (a) In uncooked...

21 CFR 556.240 - Estradiol and related esters.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol... increments above the concentrations of estradiol naturally present in untreated animals: (a) In uncooked...

21 CFR 556.240 - Estradiol and related esters.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol... increments above the concentrations of estradiol naturally present in untreated animals: (a) In uncooked...

21 CFR 556.240 - Estradiol and related esters.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol... increments above the concentrations of estradiol naturally present in untreated animals: (a) In uncooked...

Polychlorinated Biphenyl Congeners that Increase the Glucuronidation and Biliary Excretion of Thyroxine Are Distinct from the Congeners that Enhance the Serum Disappearance of Thyroxine

PubMed Central

Martin, L. A.; Wilson, D. T.; Reuhl, K. R.; Gallo, M. A.

2012-01-01

Polychlorinated biphenyl (PCB) congeners differentially reduce serum thyroxine (T4) in rats, but little is known about their ability to affect biliary excretion of T4. Thus, male Sprague-Dawley rats were orally administered Aroclor-1254, Aroclor-1242 (32 mg/kg per day), PCB-95, PCB-99, PCB-118 (16 mg/kg per day), PCB-126 (40 μg/kg per day), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (3.9 μg/kg per day), or corn oil for 7 days. Twenty-four hours after the last dose, [125I]T4 was administered intravenously, and blood, bile, and urine samples were collected for quantifying [125I]T4 and in bile [125I]T4 metabolites. Serum T4 concentrations were reduced by all treatments, but dramatic reductions occurred in response to Aroclor-1254, PCB-99 [phenobarbital (PB)-type congener], and PCB-118 (mixed-type congener). None of the treatments increased urinary excretion of [125I]T4. Aroclor-1254, PCB-118, TCDD, and PCB-126 (TCDD-type congener) increased biliary excretion of T4-glucuronide by 850, 756, 710, and 573%, respectively, corresponding to marked induction of hepatic UDP-glucuronosyltransferase (UGT) activity toward T4. PCB-95 and PCB-99 did not induce UGT activity; therefore, the increased biliary excretion of T4-glucuronide was related to the affinity of congeners for the aryl hydrocarbon receptor. The disappearance of [125I]T4 from serum was rapid (within 15-min) and was increased by Aroclor-1254, PCB-99 and PCB-118. Thus, reductions in serum T4 in response to PCBs did not always correspond with UGT activity toward T4 or with increased biliary excretion of T4-glucuronide. The rapid disappearance of [125I]T4 from the serum of rats treated with PB-like PCBs suggests that increased tissue uptake of T4 is an additional mechanism by which PCBs may reduce serum T4. PMID:22187485

Net trophic transfer efficiencies of polychlorinated biphenyl congeners to lake whitefish (Coregonus clupeaformis) from their food

USGS Publications Warehouse

Madenjian, C.P.; O'Connor, D.V.; Rediske, R.R.; O'Keefe, J. P.; Pothoven, S.A.

2008-01-01

Lake whitefish (Coregonus clupeaformis) were fed rainbow smelt (Osmerus mordax) in four laboratory tanks over a 133-d experiment. At the start of the experiment, 10 to 14 of the fish in each tank were sacrificed, and the concentrations of 40 polychlorinated biphenyl (PCB) congeners within these fish were determined. Polychlorinated biphenyl congener concentrations were also determined in the 15 lake whitefish remaining in each of the four tanks at the end of the experiment as well as in the rainbow smelt fed to the lake whitefish. Each lake whitefish was weighed at the start and the end of the experiment, and the amount of food eaten by the lake whitefish during the experiment was tracked. Using these measurements, net trophic transfer efficiency (??) from the rainbow smelt to the lake whitefish in each of the four tanks was calculated for each of the 40 PCB congeners. Results showed that ?? decreased exponentially as log KOW for the congeners increased from 6 to 8. Further, ?? averaged 0.70 for the tetrachloro congeners but averaged only 0.45 for the higher chlorinated congeners. ?? 2008 SETAC.

Bioaccumulation of toxaphene congeners in the lake superior food web

USGS Publications Warehouse

Muir, D.C.G.; Whittle, D.M.; De Vault, D. S.; Bronte, C.R.; Karlsson, H.; Backus, S.; Teixeira, C.

2004-01-01

The bioaccumulation and biotransformation of toxaphene was examined in the food webs of Lake Superior and Siskiwit Lake (Isle Royale) using congener specific analysis as well as stable isotope ratios of carbon and nitrogen to characterize food webs. Toxaphene concentrations (calculated using technical toxaphene) in lake trout (Salvelinus namaycush) from the western basin of Lake Superior (N = 95) averaged (±SD) 889 ± 896 ng/g wet wt and 60 ± 34 ng/g wet wt in Siskiwit Lake. Major congeners in lake trout were B8-789 (P38), B8-2226 (P44), B9-1679 (P50), and B9-1025 (P62). Toxaphene concentrations were found to vary seasonally, especially in lower food web organisms in Lake Superior and to a lesser extent in Siskiwit Lake. Toxaphene concentrations declined significantly in lake herring (Coregonus artedii), rainbow smelt (Omerus mordax), and slimy sculpin (Cottus cognatus) as well as in zooplankton (> 102 &mn;m) and Mysis (Mysis relicta) between May and October. The seasonal variation may reflect seasonal shifts in the species abundance within the zooplankton community. Trophic magnification factors (TMF) derived from regressions of toxaphene congener concentrations versus δ15N were > 1 for most octa- and nonachlorobornanes in Lake Superior except B8-1413 (P26) and B9-715. Log bioaccumulation factors (BAFs) for toxaphene congeners in lake trout (ng/g lipid/ng/L dissolved) ranged from 4.54 to 9.7 and were significantly correlated with log octanol-water partition coefficients. TMFs observed for total toxaphene and congener B9-1679 in Lake Superior were similar to those in Arctic lakes, as well as to previous studies in the Great Lakes, which suggests that the bioaccumulation behavior of toxaphene is similar in pelagic food webs of large, cold water systems. However, toxaphene concentrations were lower in lake trout from Siskiwit Lake and lakes in northwestern Ontario than in Lake Superior possibly because of shorter food chains and greater reliance on zooplankton or

Speed congenics: accelerated genome recovery using genetic markers.

PubMed

Visscher, P M

1999-08-01

Genetic markers throughout the genome can be used to speed up 'recovery' of the recipient genome in the backcrossing phase of the construction of a congenic strain. The prediction of the genomic proportion during backcrossing depends on the assumptions regarding the distribution of chromosome segments, the population structure, the marker spacing and the selection strategy. In this study simulation was used to investigate the rate of recovery of the recipient genome for a mouse, Drosophila and Arabidopsis genome. It was shown that an incorrect assumption of a binomial distribution of chromosome segments, and failing to take account of a reduction in variance in genomic proportion due to selection, can lead to a downward bias of up to two generations in the estimation of the number of generations required for the formation of a congenic strain.

Bioinspired chemical synthesis of monomeric and dimeric stephacidin A congeners

NASA Astrophysics Data System (ADS)

Mukai, Ken; de Sant'ana, Danilo Pereira; Hirooka, Yasuo; Mercado-Marin, Eduardo V.; Stephens, David E.; Kou, Kevin G. M.; Richter, Sven C.; Kelley, Naomi; Sarpong, Richmond

2018-01-01

Stephacidin A and its congeners are a collection of secondary metabolites that possess intriguing structural motifs. They stem from unusual biosynthetic sequences that lead to the incorporation of a prenyl or reverse-prenyl group into a bicyclo[2.2.2]diazaoctane framework, a chromene unit or the vestige thereof. To complement biosynthetic studies, which normally play a significant role in unveiling the biosynthetic pathways of natural products, here we demonstrate that chemical synthesis can provide important insights into biosynthesis. We identify a short total synthesis of congeners in the reverse-prenylated indole alkaloid family related to stephacidin A by taking advantage of a direct indole C6 halogenation of the related ketopremalbrancheamide. This novel strategic approach has now made possible the syntheses of several natural products, including malbrancheamides B and C, notoamides F, I and R, aspergamide B, and waikialoid A, which is a heterodimer of avrainvillamide and aspergamide B. Our approach to the preparation of these prenylated and reverse-prenylated indole alkaloids is bioinspired, and may also inform the as-yet undetermined biosynthesis of several congeners.

Estradiol-dependent modulation of auditory processing and selectivity in songbirds

PubMed Central

Maney, Donna; Pinaud, Raphael

2011-01-01

The steroid hormone estradiol plays an important role in reproductive development and behavior and modulates a wide array of physiological and cognitive processes. Recently, reports from several research groups have converged to show that estradiol also powerfully modulates sensory processing, specifically, the physiology of central auditory circuits in songbirds. These investigators have discovered that (1) behaviorally-relevant auditory experience rapidly increases estradiol levels in the auditory forebrain; (2) estradiol instantaneously enhances the responsiveness and coding efficiency of auditory neurons; (3) these changes are mediated by a non-genomic effect of brain-generated estradiol on the strength of inhibitory neurotransmission; and (4) estradiol regulates biochemical cascades that induce the expression of genes involved in synaptic plasticity. Together, these findings have established estradiol as a central regulator of auditory function and intensified the need to consider brain-based mechanisms, in addition to peripheral organ dysfunction, in hearing pathologies associated with estrogen deficiency. PMID:21146556

Estradiol Increases Mucus Synthesis in Bronchial Epithelial Cells

PubMed Central

Tam, Anthony; Wadsworth, Samuel; Dorscheid, Delbert; Man, Shu-Fan Paul; Sin, Don D.

2014-01-01

Airway epithelial mucus hypersecretion and mucus plugging are prominent pathologic features of chronic inflammatory conditions of the airway (e.g. asthma and cystic fibrosis) and in most of these conditions, women have worse prognosis compared with male patients. We thus investigated the effects of estradiol on mucus expression in primary normal human bronchial epithelial cells from female donors grown at an air liquid interface (ALI). Treatment with estradiol in physiological ranges for 2 weeks caused a concentration-dependent increase in the number of PAS-positive cells (confirmed to be goblet cells by MUC5AC immunostaining) in ALI cultures, and this action was attenuated by estrogen receptor beta (ER-β) antagonist. Protein microarray data showed that nuclear factor of activated T-cell (NFAT) in the nuclear fraction of NHBE cells was increased with estradiol treatment. Estradiol increased NFATc1 mRNA and protein in ALI cultures. In a human airway epithelial (1HAE0) cell line, NFATc1 was required for the regulation of MUC5AC mRNA and protein. Estradiol also induced post-translational modification of mucins by increasing total fucose residues and fucosyltransferase (FUT-4, -5, -6) mRNA expression. Together, these data indicate a novel mechanism by which estradiol increases mucus synthesis in the human bronchial epithelium. PMID:24964096

Correlation between human maternal-fetal placental transfer and molecular weight of PCB and dioxin congeners/isomers.

PubMed

Mori, Chisato; Nakamura, Noriko; Todaka, Emiko; Fujisaki, Takeyoshi; Matsuno, Yoshiharu; Nakaoka, Hiroko; Hanazato, Masamichi

2014-11-01

Establishing methods for the assessment of fetal exposure to chemicals is important for the prevention or prediction of the child's future disease risk. In the present study, we aimed to determine the influence of molecular weight on the likelihood of chemical transfer from mother to fetus via the placenta. The correlation between molecular weight and placental transfer rates of congeners/isomers of polychlorinated biphenyls (PCBs) and dioxins was examined. Twenty-nine sample sets of maternal blood, umbilical cord, and umbilical cord blood were used to measure PCB concentration, and 41 sample sets were used to analyze dioxins. Placental transfer rates were calculated using the concentrations of PCBs, dioxins, and their congeners/isomers within these sample sets. Transfer rate correlated negatively with molecular weight for PCB congeners, normalized using wet and lipid weights. The transfer rates of PCB or dioxin congeners differed from those of total PCBs or dioxins. The transfer rate for dioxin congeners did not always correlate significantly with molecular weight, perhaps because of the small sample size or other factors. Further improvement of the analytical methods for dioxin congeners is required. The findings of the present study suggested that PCBs, dioxins, or their congeners with lower molecular weights are more likely to be transferred from mother to fetus via the placenta. Consideration of chemical molecular weight and transfer rate could therefore contribute to the assessment of fetal exposure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Estradiol blood test

MedlinePlus

... development Changes of the outer genitals Distribution of body fat Menopause In men, a small amount of estradiol ... syndrome , Turner syndrome Rapid weight loss or low body fat Risks Veins and arteries vary in size from ...

Congener specificity in the accumulation of dioxins and dioxin-like compounds in zucchini plants grown hydroponically.

PubMed

Inui, Hideyuki; Wakai, Taketo; Gion, Keiko; Yamazaki, Kiyoshi; Kim, Yun-Seok; Eun, Heesoo

2011-01-01

Zucchini cultivars Cucurbita pepo subsp. ovifera cv. Patty Green and subsp. pepo cv. Gold Rush were cultivated hydroponically in a nutrient solution supplemented with a mixture of dioxins and dioxin-like compounds. Patty Green and Gold Rush showed low and high accumulation of these compounds in the aerial parts respectively. In both cultivars, the accumulation of each congener negatively depended on its hydrophobicity. This suggests that desorption and solubilization were partly responsible for congener specificity of accumulation, since this was not found in soil experiments. In contrast, no clear difference in accumulation in the roots was observed between the cultivars, whereas the translocation factors, which are indicators of efficient translocation from the roots to the aerial parts, differed among the congeners hydrophobicity-dependently. There were positive correlations between accumulation in the roots and the hydrophobicity of the polychlorinated biphenyl congeners in both cultivars. These results indicate that translocation was also partly responsible for the congener specificity and accumulation concentrations.

Quantification of all 209 PCB congeners in blood-Can indicators be used to calculate the total PCB blood load?

PubMed

Kraft, M; Rauchfuss, K; Sievering, S; Wöckner, M; Neugebauer, F; Fromme, H

2017-03-01

Polychlorinated biphenyls (PCBs) are a substance group of 209 theoretically possible compounds. The human body burden of PCBs is commonly calculated based on so-called indicator congeners such as PCB 138, PCB 153 and PCB 180, which are analyzed in human blood. The German "Human Biomonitoring (HBM) Commission" assumes that the sum of these indicator congeners multiplied by a factor of 2 represents the total PCB burden. This norm is based on data obtained from exposure studies after dietary intake. Data from indoor air shows a different congener pattern, which might lead to a relatively higher intake of lower chlorinated PCBs by inhalation. In two independent studies with adult participants from two regions in Germany, we measured all 209 PCB congeners in 44 whole blood and 42 plasma samples. Participants from the whole blood study group had additional exposure to PCBs via indoor air. With our analytical method, 141 individual PCB congeners, 27 coeluted pairs of PCB congeners and 2 records of 3 and 4 coeluted PCBs could be determined. Thus, 172 analysis results were reported per sample. In the whole blood samples, 50 congeners showed values below the limit of quantification (LOQ), whereas 94 congeners could not be detected in any of plasma samples. Total PCB concentrations (Σ 209 PCB congeners, incl. ½ LOQ) in the whole blood samples ranged from 99 to 2152ng PCB/g lipid (Median: 454ng/g lipid; 95th Percentile: 1404ng/g lipid). The sum of all 209 measured PCB (incl. ½ LOQ) in plasma samples showed levels between 52 and 933ng PCB/g lipid (Median: 226ng/g lipid; 95th Percentile: 642ng/g lipid). Our results show that the burden of PCBs on the human body is caused mainly by the three highly chlorinated indicator congeners PCB 138, PCB 153 and PCB 180. In median approximately 50% of the total PCB content in human whole blood or plasma samples can be attributed to these congeners. Total PCB, calculated by multiplying the sum of the three indicator congeners by 2, showed

Estradiol-promoted accumulation of receptor in nuclei of porcine endometrium cells. Immunogold electron microscopy of resting and estradiol-stimulated cells.

PubMed

Sierralta, W D; Jakob, F; Thole, H; Engel, P; Jungblut, P W

1992-01-01

Endometrium was collected by curettage from castrated pigs, either untreated or exposed to estradiol in vivo by intrauterine injection, and processed for electron microscopy. The resin LR Gold was used for embedding, and sections were floated on droplets of 10 nm diameter gold particles, coated with the immunoglobulin-G1 (IgG1) fraction or its Fab2 fragment of a monospecific polyclonal antiserum raised in goats against the C-terminal half of the estradiol receptor. On average, only one gold particle per microns 2 became attached in the cytoplasmic area of untreated cells, whereas four were found over the nuclear area. These figures rose to 2-3/microns 2 and 15-26/microns 2, respectively, within 10 min after exposure to estradiol. The labeling intensities of nuclei in cell clusters and of coprocessed nuclei released from cells ruptured during curettage were identical in all situations. Nuclear pores were frequently tagged after estradiol treatment. The proportions of tagging densities in nuclei of untreated and estradiol-exposed cells corresponded to those of receptor contents measured in extracts of isolated nuclei by ligand binding. This correlation was not seen for the cytoplasmic compartment of untreated cells, the scarce tagging of which is interpreted by hidden antigenic determinants. Our morphological analyses support the conclusions drawn from biochemical data (Sierralta et al., 1992) of an estradiol-promoted translocation of receptor from the cytoplasm into the nucleus.

Determination of polychlorinated biphenyl congeners and chlorinated pesticides in a fish tissue standard reference material.

PubMed

Poster, Dianne L; Kucklick, John R; Schantz, Michele M; Porter, Barbara J; Leigh, Stefan D; Wise, Stephen A

2003-01-01

The concentrations of a wide range of polychlorinated biphenyl congeners (PCBs) and chlorinated pesticides in a fish tissue Standard Reference Material (SRM) have been determined using multiple methods of analysis. This material, SRM 1946, Lake Superior Fish Tissue, was recently issued by the National Institute of Standards and Technology (NIST) and complements a suite of marine environmental natural-matrix SRMs that are currently available from NIST for the determination of organic contaminants such as aliphatic hydrocarbons, polycyclic aromatic hydrocarbons (PAHs), PCBs, and chlorinated pesticides. SRM 1946 is a fresh tissue homogenate (frozen) prepared from filleted adult lake trout (Salvelinus namaycush namaycush) collected from the Apostle Islands region of Lake Superior. SRM 1946 has certified and reference concentrations for PCB congeners, including the three non- ortho PCB congeners, and chlorinated pesticides. Certified concentrations are available for 30 PCB congeners and 15 chlorinated pesticides. Reference concentrations are available for 12 PCB congeners and 2 chlorinated pesticides. In addition, SRM 1946 is characterized for additional chemical constituents and properties: fatty acids, extractable fat, methylmercury, total mercury, selected trace elements, proximates, and caloric content. The characterization of chlorinated compounds is described in this paper with an emphasis on the approach used for the certification of the concentrations of PCB congeners and chlorinated pesticides. The PCB congener and chlorinated pesticide data are also compared to concentrations in other marine natural-matrix reference materials available from NIST (fish oil, mussel tissue, whale blubber, and a second fresh frozen fish tissue homogenate prepared from filleted adult lake trout collected from Lake Michigan) and from other organizations such as the National Research Council Canada (ground whole carp), the International Atomic Energy Agency (fish homogenate), and the

Estradiol Membrane-Initiated Signaling and Female Reproduction.

PubMed

Micevych, Paul E; Wong, Angela May; Mittelman-Smith, Melinda Anne

2015-07-01

The discoveries of rapid, membrane-initiated steroid actions and central nervous system steroidogenesis have changed our understanding of the neuroendocrinology of reproduction. Classical nuclear actions of estradiol and progesterone steroids affecting transcription are essential. However, with the discoveries of membrane-associated steroid receptors, it is becoming clear that estradiol and progesterone have neurotransmitter-like actions activating intracellular events. Ultimately, membrane-initiated actions can influence transcription. Estradiol membrane-initiated signaling (EMS) modulates female sexual receptivity and estrogen feedback regulating the luteinizing hormone (LH) surge. In the arcuate nucleus, EMS activates a lordosis-regulating circuit that extends to the medial preoptic nucleus and subsequently to the ventromedial nucleus (VMH)--the output from the limbic and hypothalamic regions. Here, we discuss how EMS leads to an active inhibition of lordosis behavior. To stimulate ovulation, EMS facilitates astrocyte synthesis of progesterone (neuroP) in the hypothalamus. Regulation of GnRH release driving the LH surge is dependent on estradiol-sensitive kisspeptin (Kiss1) expression in the rostral periventricular nucleus of the third ventricle (RP3V). NeuroP activation of the LH surge depends on Kiss1, but the specifics of signaling have not been well elucidated. RP3V Kiss1 neurons appear to integrate estradiol and progesterone information which feeds back onto GnRH neurons to stimulate the LH surge. In a second population of Kiss1 neurons, estradiol suppresses the surge but maintains tonic LH release, another critical component of the estrous cycle. Together, evidence suggests that regulation of reproduction involves membrane action of steroids, some of which are synthesized in the brain. © 2015 American Physiological Society.

Concentrations and congener profiles of chlorinated paraffins in domestic polymeric products in China.

PubMed

Wang, Chu; Gao, Wei; Liang, Yong; Wang, Yawei; Jiang, Guibin

2018-03-21

Chlorinated paraffins (CPs) are widely used in domestic polymeric products as plasticizers and fire retardants. In this study, concentrations and congener profiles of short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs) were investigated in domestic polymeric products, including plastics, rubber and food packaging in China. The average concentrations of SCCPs in polyethylene terephthalate (PET), polypropylene (PP), polyethylene (PE) and food packaging were 234, 3968, 150 and 188 ng/g, respectively and the corresponding average concentrations of MCCPs in these samples were 37.4, 2537, 208 and 644 ng/g, respectively. The concentrations of CPs in rubber and polyvinylchloride (PVC) were significantly higher than in other matrices. The highest concentrations of SCCPs and MCCPs were found in a PVC cable sheath with 191 mg/g and 145 mg/g, respectively. Congener group profiles analysis indicated C 11 - and C 13 -congener groups were predominant in carbon homologues of SCCPs, and C 14 -congener groups were predominant in MCCPs. High levels of SCCPs and MCCPs in domestic polymeric products implied that they might be a significant source to the environment and human exposure. Copyright © 2018. Published by Elsevier Ltd.

Functionalized Congeners of P2Y1 Receptor Antagonists:

DOE Office of Scientific and Technical Information (OSTI.GOV)

de Castro, Sonia; Maruoka, Hiroshi; Hong, Kunlun

2010-01-01

The P2Y{sub 1} receptor is a prothrombotic G protein-coupled receptor (GPCR) activated by ADP. Preference for the North (N) ring conformation of the ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of the P2Y{sub 1} receptor was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute. A series of covalently linkable N{sup 6}-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphates containing extended 2-alkynyl chains was designed, and binding affinity at the human (h) P2Y{sub 1} receptor determined. The chain of these functionalized congeners contained hydrophilic moieties, a reactive substituent, or biotin, linked via an amide. Variation of the chain length and position of anmore » intermediate amide group revealed high affinity of carboxylic congener 8 (K{sub i} 23 nM) and extended amine congener 15 (K{sub i} 132 nM), both having a 2-(1-pentynoyl) group. A biotin conjugate 18 containing an extended {epsilon}-aminocaproyl spacer chain exhibited higher affinity than a shorter biotinylated analogue. Alternatively, click coupling of terminal alkynes of homologous 2-dialkynyl nucleotide derivatives to alkyl azido groups produced triazole derivatives that bound to the P2Y{sub 1} receptor following deprotection of the bisphosphate groups. The preservation of receptor affinity of the functionalized congeners was consistent with new P2Y{sub 1} receptor modeling and ligand docking. Attempted P2Y{sub 1} antagonist conjugation to PAMAM dendrimer carriers by amide formation or palladium-catalyzed reaction between an alkyne on the dendrimer and a 2-iodopurine-derivatized nucleotide was unsuccessful. A dialkynyl intermediate containing the chain length favored in receptor binding was conjugated to an azide-derivatized dendrimer, and the conjugate inhibited ADP-promoted human platelet aggregation. This is the first example of attaching a strategically functionalized P2Y receptor antagonist to a PAMAM

Elimination Rates of Dioxin Congeners in Former Chlorophenol Workers from Midland, Michigan

PubMed Central

Collins, James J.; Bodner, Kenneth M.; Wilken, Michael; Bodnar, Catherine M.

2012-01-01

Background: Exposure reconstructions and risk assessments for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxins rely on estimates of elimination rates. Limited data are available on elimination rates for congeners other than TCDD. Objectives: We estimated apparent elimination rates using a simple first-order one-compartment model for selected dioxin congeners based on repeated blood sampling in a previously studied population. Methods: Blood samples collected from 56 former chlorophenol workers in 2004–2005 and again in 2010 were analyzed for dioxin congeners. We calculated the apparent elimination half-life in each individual for each dioxin congener and examined factors potentially influencing elimination rates and the impact of estimated ongoing background exposures on rate estimates. Results: Mean concentrations of all dioxin congeners in the sampled participants declined between sampling times. Median apparent half-lives of elimination based on changes in estimated mass in the body were generally consistent with previous estimates and ranged from 6.8 years (1,2,3,7,8,9-hexachlorodibenzo-p-dioxin) to 11.6 years (pentachlorodibenzo-p-dioxin), with a composite half-life of 9.3 years for TCDD toxic equivalents. None of the factors examined, including age, smoking status, body mass index or change in body mass index, initial measured concentration, or chloracne diagnosis, was consistently associated with the estimated elimination rates in this population. Inclusion of plausible estimates of ongoing background exposures decreased apparent half-lives by approximately 10%. Available concentration-dependent toxicokinetic models for TCDD underpredicted observed elimination rates for concentrations < 100 ppt. Conclusions: The estimated elimination rates from this relatively large serial sampling study can inform occupational and environmental exposure and serum evaluations for dioxin compounds. PMID:23063871

Congenic mice demonstrate the presence of QTLs conferring obesity and hypercholesterolemia on chromosome 1 in the TALLYHO mouse.

PubMed

Parkman, Jacaline K; Denvir, James; Mao, Xia; Dillon, Kristy D; Romero, Sofia; Saxton, Arnold M; Kim, Jung Han

2017-12-01

The TALLYHO (TH) mouse presents a metabolic syndrome of obesity, type 2 diabetes, and hyperlipidemia. Highly significant quantitative trait loci (QTLs) linked to adiposity and hypercholesterolemia were previously identified on chromosome (Chr) 1 in a genome-wide scan of F2 mice from C57BL/6J (B6) x TH. In this study, we generated congenic mouse strains that carry the Chr 1 QTLs derived from TH on a B6 background; B6.TH-Chr1-128Mb (128Mb in size) and B6.TH-Chr1-92Mb (92Mb in size, proximally overlapping). We characterized these congenic mice on chow and high fat (HF) diets. On chow, B6.TH-Chr1-128Mb congenic mice exhibited a slightly larger body fat mass compared with B6.TH-Chr1-92Mb congenic and B6 mice, while body fat mass between B6.TH-Chr1-92Mb congenic and B6 mice was comparable. Plasma total cholesterol levels were significantly higher in B6.TH-Chr1-128Mb congenics compared to B6.TH-Chr1-92Mb congenic and B6 mice. Again, there was no difference in plasma total cholesterol levels between B6.TH-Chr1-92Mb congenic and B6 mice. All animals gained more body fat and exhibited higher plasma total cholesterol levels when fed HF diets than fed chow, but these increases were greater in B6.TH-Chr1-128Mb congenics than in B6.TH-Chr1-92Mb congenic and B6 mice. These results confirmed the effect of the 128Mb TH segment from Chr 1 on body fat and plasma cholesterol values and showed that the distal segment of Chr 1 from TH is necessary to cause both phenotypes. Through bioinformatic approaches, we generated a list of potential candidate genes within the distal region of Chr 1 and tested Ifi202b and Apoa2. We conclude that Chr 1 QTLs largely confer obesity and hypercholesterolemia in TH mice and can be promising targets for identifying susceptibility genes. Congenic mouse strains will be a valuable resource for gene identification.

Inhibition of Estradiol Synthesis Impairs Fear Extinction in Male Rats

ERIC Educational Resources Information Center

Graham, Bronwyn M.; Milad, Mohammed R.

2014-01-01

Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole,…

Origin of estradiol fatty acid esters in human ovarian follicular fluid.

PubMed

Pahuja, S L; Kim, A H; Lee, G; Hochberg, R B

1995-03-01

The estradiol fatty acid esters are the most potent of the naturally occurring steroidal estrogens. These esters are present predominantly in fat, where they are sequestered until they are hydrolyzed by esterases. Thus they act as a preformed reservoir of estradiol. We have previously shown that ovarian follicular fluid from patients undergoing gonadotropin stimulation contains very high amounts of estradiol fatty acid esters (approximately 10(-7) M). The source of these esters is unknown. They can be formed by esterification of estradiol in the follicular fluid by lecithin:cholesterol acyltransferase (LCAT), or in the ovary by an acyl coenzyme A:acyltransferase. In order to determine which of these enzymatic processes is the source of the estradiol esters in the follicular fluid, we incubated [3H]estradiol with follicular fluid and cells isolated from human ovarian follicular fluid and characterized the fatty acid composition of the [3H]estradiol esters biosynthesized in each. In addition, we characterized the endogenous estradiol fatty acid esters in the follicular fluid and compared them to the biosynthetic esters. The fatty acid composition of the endogenous esters was different than those synthesized by the cellular acyl coenzyme A:acyltransferase, and the same as the esters synthesized by LCAT, demonstrating that the esters are produced in situ in the follicular fluid. Although the role of these estradiol esters in the ovary is not known, given their remarkable estrogenic potency it is highly probable that they have an important physiological role.

Basal and dynamic relationships between implicit power motivation and estradiol in women.

PubMed

Stanton, Steven J; Schultheiss, Oliver C

2007-12-01

This study investigated basal and reciprocal relationships between implicit power motivation (n Power), a preference for having impact and dominance over others, and both salivary estradiol and testosterone in women. 49 participants completed the Picture Story Exercise, a measure of n Power. During a laboratory contest, participants competed in pairs on a cognitive task and contest outcome (win vs. loss) was experimentally varied. Estradiol and testosterone levels were determined in saliva samples collected at baseline and several times post-contest, including 1 day post-contest. n Power was positively associated with basal estradiol concentrations. The positive correlation between n Power and basal estradiol was stronger in single women, women not taking oral contraceptives, or in women with low-CV estradiol samples than in the overall sample of women. Women's estradiol responses to a dominance contest were influenced by the interaction of n Power and contest outcome: estradiol increased in power-motivated winners but decreased in power-motivated losers. For power-motivated winners, elevated levels of estradiol were still present the day after the contest. Lastly, n Power and estradiol did not correlate with self-reported dominance and correlated negatively with self-reported aggression. Self-reported dominance and aggression did not predict estradiol changes as a function of contest outcome. Overall, n Power did not predict basal testosterone levels or testosterone changes as a function of dominance contest outcome.

Net trophic transfer efficiencies of polychlorinated biphenyl congeners to lake trout (Salvelinus namaycush) from its prey

USGS Publications Warehouse

Madenjian, Charles P.; David, Solomon R.; Rediske, Richard R.; O’Keefe, James P.

2012-01-01

Lake trout (Salvelinus namaycush) were fed bloater (Coregonus hoyi) in eight laboratory tanks over a 135-d experiment. At the start of the experiment, four to nine fish in each tank were sacrificed, and the concentrations of 75 polychlorinated biphenyl (PCB) congeners within these fish were determined. Polychlorinated biphenyl congener concentrations were also determined in the 10 lake trout remaining in each of the eight tanks at the end of the experiment as well as in the bloater fed to the lake trout. Each lake trout was weighed at the start and the end of the experiment, and the amount of food eaten by the lake trout was recorded. Using these measurements, net trophic transfer efficiency (γ) from the bloater to the lake trout in each of the eight tanks was calculated for each of the 75 congeners. Results showed that γ did not vary significantly with the degree of chlorination of the PCB congeners, and γ averaged 0.66 across all congeners. However,γ did show a slight, but significant, decrease as logKOW increased from 6.0 to 8.2. Activity level of the lake trout did not have a significant effect on γ.

Estradiol and cognitive function: Past, present and future

PubMed Central

Luine, Victoria N.

2014-01-01

A historical perspective on estradiol’s enhancement of cognitive function is presented, and research, primarily in animals, but also in humans, is reviewed. Data regarding the mechanisms underlying the enhancements are discussed. Newer studies showing rapid effects of estradiol on consolidation of memory through membrane interactions and activation of inter-cellular signaling pathways are reviewed as well as studies focused on traditional genomic mechanisms. Recent demonstrations of intra-neuronal estradiol synthesis and possible actions as a neurosteroid to promote memory are discussed. This information is applied to the critical issue of the current lack of effective hormonal (or other) treatments for cognitive decline associated with menopause and aging. Finally, the critical period hypothesis for estradiol effects is discussed along with novel strategies for hormone/drug development. Overall, the historical record documents that estradiol positively impacts some aspects of cognitive function, but effective therapeutic interventions using this hormone have yet to be realized. PMID:25205317

Elevated PCDD/F levels and distinctive PCDD/F congener profiles in free range eggs.

PubMed

Hsu, Jing-Fang; Chen, Chun; Liao, Pao-Chi

2010-07-14

Chicken eggs are one of the most important foods in the human diet all over the world, and the demand for eggs from free range hens has steadily increased. Congener-specific analyses of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were performed on 6 free range and 12 caged chicken egg samples collected in Taiwan. The mean level of PCDD/Fs in the free range egg samples was 5.7 (1.79/0.314) times higher than those in the caged egg samples. Principle component analysis revealed that at least three characteristic patterns of PCDD/F congener were observed among the 18 egg samples. The different PCDD/F congener patterns between free range and caged egg samples may reflect distinctive exposure scenarios among the free range and caged hens. We suggest that the differences of PCDD/F levels and congener patterns between free range and caged egg samples give rise to the issues related to the safety of eating free range chicken eggs. The present data may provide useful information for further investigation of the possible PCDD/F sources in the contaminated free range eggs.

The effects of drospirenone-ethinyl estradiol and drospirenone-ethinyl estradiol + metformin on ovarian ultrasonographic markers, body fat mass index, leptin, and ghrelin.

PubMed

Cakiroglu, Y; Vural, B; Isgoren, S

2013-07-01

Polycystic ovary syndrome (PCOS) is considered as the most common endocrinopathy among women of reproductive age. Oral contraceptives (OCs) and metformin are one of the main drug groups in the long-term treatment of PCOS. This study was undertaken to investigate the effects of drospirenone-ethinyl estradiol and drospirenone-ethinyl estradiol + metformin on ultrasonographic markers, body fat mass (BFM) index, leptin-ghrelin. This was a prospective clinical study conducted at Kocaeli University Department of Obstetrics and Gynecology on 42 PCOS patients. Patients were randomly allocated into two groups [Group I (n = 22): drospirenone-ethinyl estradiol (DEE); Group II (n = 20): drospirenone-ethinyl estradiol + metformin (M)] according to Body Mass Index (BMI) findings. Patients were evaluated in terms of leptin-ghrelin, ultrasound, and body fat distribution before and 6 months after therapy. Main outcome measures were to investigate the effects of drospirenone-ethinyl estradiol and drospirenone-ethinyl estradiol + metformin on ovarian ultrasonographic markers, BFM index, leptin, and ghrelin. In patients with higher BMI, ovarian volume, numbers of follicles, stromal area, and echogenicity have been reported to be larger. In group II, a negative correlation between ghrelin and abdominal fat mass after treatment has been noted, whereas in group I a positive correlation between leptin and abdominal fat mass after treatment has been observed. Addition of metformin could have beneficial effects on abdominal fat mass. Stromal area measurement and assessment of fat mass with Dual X-ray Absorptiometry could be helpful as a quantitative way of measurement.

Estradiol alters body temperature regulation in the female mouse.

PubMed

Krajewski-Hall, Sally J; Blackmore, Elise M; McMinn, Jessi R; Rance, Naomi E

2018-01-01

Hot flushes are due to estrogen withdrawal and characterized by the episodic activation of heat dissipation effectors. Recent studies (in humans and rats) have implicated neurokinin 3 (NK 3 ) receptor signaling in the genesis of hot flushes. Although transgenic mice are increasingly used for biomedical research, there is limited information on how 17β-estradiol and NK 3 receptor signaling alters thermoregulation in the mouse. In this study, a method was developed to measure tail skin temperature (T SKIN ) using a small data-logger attached to the surface of the tail, which, when combined with a telemetry probe for core temperature (T CORE ), allowed us to monitor thermoregulation in freely-moving mice over long durations. We report that estradiol treatment of ovariectomized mice reduced T CORE during the light phase (but not the dark phase) while having no effect on T SKIN or activity. Estradiol also lowered T CORE in mice exposed to ambient temperatures ranging from 20 to 36°C. Unlike previous studies in the rat, estradiol treatment of ovariectomized mice did not reduce T SKIN during the dark phase. Subcutaneous injections of an NK 3 receptor agonist (senktide) in ovariectomized mice caused an acute increase in T SKIN and a reduction in T CORE , consistent with the activation of heat dissipation effectors. These changes were reduced by estradiol, suggesting that estradiol lowers the sensitivity of central thermoregulatory pathways to NK 3 receptor activation. Overall, we show that estradiol treatment of ovariectomized mice decreases T CORE during the light phase, reduces the thermoregulatory effects of senktide and modulates thermoregulation differently than previously described in the rat.

Study on the impact of industrial flue gases on the PCDD/Fs congener profile in ambient air.

PubMed

Węgiel, Małgorzata; Chrząszcz, Ryszard; Maślanka, Anna; Grochowalski, Adam

2014-11-01

The aim of this study was to examine the impact of emissions from combustion processes from sinter, medical, waste and sewage waste incineration plants on the PCDD and PCDF congener profile in ambient air in Krakow (city in Poland). The subject matter of the study were air samples from the outskirts and the city center. It was found that in flue gases from industrial sources and in ambient air the share of PCDF congeners in relation to the total content of PCDD/Fs was higher than the share of PCDDs. However, in air samples collected in the city center, this relationship was reversed. The PCDD congener profiles in flue gases and in air samples are comparable. However, in the samples from the city centre, the share of OCDD is significantly higher and amounts to about 80%. The PCDF congener shares show higher spatial diversity, although in all the analyzed air samples, ODCF and 1,2,3,4,6,7,8 HpCDF dominated. Analyzing the share of congeners in regard to the sum of PCDDs/Fs a mutual resemblance of air from the suburbs, exhaust gases from the sinter ore and sewage sludge incinerator plant was observed. The study showed a similarity between the profile of congeners in air from the city centre and exhaust gases from the medical waste incinerator. Copyright © 2014 Elsevier Ltd. All rights reserved.

Social regulation of plasma estradiol concentration in a female anuran

PubMed Central

Lynch, Kathleen S.; Wilczynski, Walter

2008-01-01

The behavior of an individual within a social aggregation profoundly influences behavior and physiology of other animals within the aggregation in such a way that these social interactions can enhance reproductive success, survival and fitness. This phenomenon is particularly important during the breeding season when males and female must synchronize their reproductive efforts. We examined whether exposure to conspecific social cues can elevate sex steroid levels, specifically estradiol and androgens, in female túngara frogs (Physalaemus pustulosus). We compared plasma estradiol and androgen concentrations in wild-caught females before and after exposure to either natural mate choruses or random tones. After exposure to mate choruses for 10 consecutive nights, estradiol concentrations were significantly elevated whereas there was no significant elevation in estradiol concentrations in the group of females exposed to random tones for 10 nights. Plasma androgen concentrations were not significantly changed after exposure to either natural mate choruses or random tones for 10 consecutive nights. Social modulation of estradiol concentrations may be important in maintaining a female’s reproductive state while males are chorusing. To our knowledge, this is the first study to demonstrate social regulation of estradiol concentration in female anurans. PMID:16545384

Clinical chemistry of congenic mice with quantitative trait loci for predicted responses to Trypanosoma congolense infection.

PubMed

Rathkolb, Birgit; Noyes, Harry A; Brass, Andy; Dark, Paul; Fuchs, Helmut; Gailus-Durner, Valérie; Gibson, John; de Angelis, Martin Hrabé; Ogugo, Moses; Iraqi, Fuad; Kemp, Steve J; Naessens, Jan; Pope, Mathew E; Wolf, Eckhard; Agaba, Morris

2009-09-01

Trypanosoma congolense is a protozoan parasite that causes severe diseases in livestock. Three major quantative trait loci (QTL), Tir1, Tir2, and Tir3, control the survival time of mice after infection with T. congolense. Congenic mice carrying the C57BL/6 resistance alleles on the A/J background were developed for each of these loci. The congenic mice were used to physically map the regions containing the QTL gene(s) and to investigate the physiological effect of each locus. Clinical chemistry data for infected A/J, C57BL/6, and BALB/c mice were obtained for 15 analytes at five time points. Congenic mice were assessed for survival, parasitemia, and anemia as well as seven clinical-chemical analytes. The survival times were significantly increased in the Tir1 and Tir2 mice but not Tir3 congenic mice. The survival time of the parental inbred mice correlated negatively with parasitemia but positively with alanine aminotransferase activities in serum, suggesting that inflammatory reactions in the liver had a beneficial effect possibly associated with reduced parasitemia. However, there was no difference in parasitemia or liver enzyme activities of Tir1 and Tir2 congenic mice relative to their controls, showing that survival, parasitemia, and degree of liver damage are not associated with each other, despite the correlation in the parental lines. These data suggest that the congenic loci affect survival but do not affect control of parasite number. They may therefore act by limiting the pathological consequences of T. congolense infection.

Stepping backward to improve assessment of PCB congener toxicities.

PubMed Central

Hansen, L G

1998-01-01

Polychlorinated biphenyls (PCBs) are ubiquitous global contaminants that have been intensively investigated for three decades. They are broad-acting toxicants occurring in complex mixtures and accurate risk assessment has proven to be elusive. Focusing on a limited set of end points and emphasizing a fixed set of congeners have led to more streamlined data sets that are meant to expedite hazard characterization and risk assessment for the most potent congeners--aryl hydrocarbon receptor (AhR) agonists. Unfortunately, this has made it impossible to confirm or deny significant contributions from the more prevalent components of the mixtures. PCBs may be only coincidentally present, rather than causal, in some diseases. Still, attempts to determine associations with incomplete residue data may lead to erroneous conclusions and make accurate risk assessment even more elusive. Responses not mediated through the AhR are presented and emphasize large data gaps. Dissimilar analytical reports emphasize that selection of analytes is not consistent. Collectively, these data confirm that AhR-focused objectives unintentionally created the impression that nonplanar PCBs have little if any potential for hazards to humans and wildlife. Near steady-state exposure of healthy adults are probably of minor consequence except for emerging correlations with non-Hodgkin's lymphoma; however, pulses of exposure to more labile mixtures may contribute to developmental effects without leaving a residue record. More broadly based criteria are suggested and harmonization of data collection and presentation are desirable. A more comprehensive list of PCB congeners is proposed that would provide more adequate data upon which to base associations with adverse outcomes. PMID:9539012

21 CFR 522.1940 - Progesterone and estradiol benzoate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Progesterone and estradiol benzoate. 522.1940 Section 522.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...: (1) Suckling beef calves—(i) Amount—(A) 100 milligrams (mg) progesterone and 10 mg estradiol benzoate...

21 CFR 522.1940 - Progesterone and estradiol benzoate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Progesterone and estradiol benzoate. 522.1940 Section 522.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...: (1) Suckling beef calves—(i) Amount—(A) 100 milligrams (mg) progesterone and 10 mg estradiol benzoate...

21 CFR 522.1940 - Progesterone and estradiol benzoate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Progesterone and estradiol benzoate. 522.1940 Section 522.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...: (1) Suckling beef calves—(i) Amount—(A) 100 milligrams (mg) progesterone and 10 mg estradiol benzoate...

21 CFR 522.1940 - Progesterone and estradiol benzoate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Progesterone and estradiol benzoate. 522.1940 Section 522.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...: (1) Suckling beef calves—(i) Amount—(A) 100 milligrams (mg) progesterone and 10 mg estradiol benzoate...

21 CFR 522.1940 - Progesterone and estradiol benzoate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Progesterone and estradiol benzoate. 522.1940 Section 522.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...: (1) Suckling beef calves—(i) Amount—(A) 100 milligrams (mg) progesterone and 10 mg estradiol benzoate...

Blood Test: Estradiol

MedlinePlus

... for this test. On the day of the test, having your child wear a T-shirt or short-sleeved shirt can ... The blood sample will be processed by a machine. The results usually are available within a few days. Risks The estradiol blood test is considered a safe procedure. However, as with ...

Serum PCB levels and congener profiles among US construction workers

PubMed Central

Herrick, Robert F; Meeker, John D; Hauser, Russ; Altshul, Larisa; Weymouth, George A

2007-01-01

Background The presence of PCB in caulking (sealant) material found in masonry buildings has been well-documented in several countries. A recent investigation of 24 buildings in the greater Boston area found that 8 buildings had high PCB levels in caulking materials used around window frames and in joints between masonry blocks. Workers removing caulking material have been shown to have elevated serum PCB levels. Methods This project compared serum PCB levels among male workers who installed and/or removed PCB-containing caulking material from buildings in the greater Boston area with reference serum PCB levels from 358 men from the same area. Serum PCB levels were measured in the same laboratory by liquid-liquid extraction, column chromatography clean-up and dual capillary column GC/microECD analysis. Results When the congener profiles were compared between the reference population and the construction workers, the serum levels of the more volatile, lighter PCBs (di-, tri-and tetrachloro, sum of IUPAC# 6–74) were substantially higher among the construction workers. One of the youngest workers had the lowest total serum PCB levels (sum of 57 congeners) of all 6 workers, but the contribution of more volatile (less chlorinated) PCB congeners (#16, 26,28,33,74,66, and 60) was markedly higher than in other 5 workers and reference men. Only this worker was working on a job that involved removing PCB caulking at the time of the blood sampling. Conclusion While the results of this pilot study are based upon small numbers (6 construction workers who handled PCB caulking), the serum PCB levels among the construction workers exceed the referents. Comparison of the congener profiles suggests that there are substantial differences between the construction workers and the general population samples. These differences, and the similarities of profiles among the construction workers strongly suggest that occupational contact with caulking material can be a major source of PCB

Estradiol concentrations and working memory performance in women of reproductive age.

PubMed

Hampson, Elizabeth; Morley, Erin E

2013-12-01

Estrogen has been proposed to exert a regulatory influence on the working memory system via actions in the female prefrontal cortex. Tests of this hypothesis have been limited almost exclusively to postmenopausal women and pharmacological interventions. We explored whether estradiol discernibly influences working memory within the natural range of variation in concentrations characteristic of the menstrual cycle. The performance of healthy women (n=39) not using hormonal contraceptives, and a control group of age- and education-matched men (n=31), was compared on a spatial working memory task. Cognitive testing was done blind to ovarian status. Women were retrospectively classified into low- or high-estradiol groups based on the results of radioimmunoassays of saliva collected immediately before and after the cognitive testing. Women with higher levels of circulating estradiol made significantly fewer errors on the working memory task than women tested under low estradiol. Pearson's correlations showed that the level of salivary estradiol but not progesterone was correlated inversely with the number of working memory errors produced. Women tested at high levels of circulating estradiol tended to be more accurate than men. Superior performance by the high estradiol group was seen on the working memory task but not on two control tasks, indicating selectivity of the effects. Consistent with previous studies of postmenopausal women, higher levels of circulating estradiol were associated with better working memory performance. These results add further support to the hypothesis that the working memory system is modulated by estradiol in women, and show that the effects can be observed under non-pharmacological conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Habitual physical activity and estradiol levels in women of reproductive age.

PubMed

Jasienska, Grazyna; Ziomkiewicz, Anna; Thune, Inger; Lipson, Susan F; Ellison, Peter T

2006-10-01

Variation in the risk of breast cancer observed among women and among populations may be explained by variation in lifetime exposure to estrogens. The suppressive effect of exercise on estradiol levels in women is well documented, but it is unknown whether habitual (i.e. typical daily) physical activity has a similar effect. Epidemiological data suggest that physical activity is one of the few modifiable factors capable of reducing the risk of breast cancer in women. We investigated whether variation in the amount of habitual activity corresponds to variation in estradiol levels in women of reproductive age. One hundred and thirty-nine regularly menstruating women 24-37 years of age collected daily saliva samples for one complete menstrual cycle and kept a daily log of physical activity. Saliva samples were analyzed for concentration of estradiol. We observed a negative relationship between habitual physical activity and salivary levels of estradiol. Mean estradiol was 21.1 pmol/l in the low, 17.9 pmol/l in the moderate and 16.6 pmol/l in the high activity group (all pairwise differences were statistically significant at P<0.009). A strong association exists between physical activity and levels of estradiol among women of reproductive age. A modern lifestyle, characterized by reduced physical activity, may therefore contribute to a rise in the levels of estradiol produced during menstrual cycles and thus to higher cumulative lifetime exposure to estradiol, resulting in a higher risk of breast cancer.

Estradiol shows anti-skin cancer activities through decreasing MDM2 expression.

PubMed

Li, Li; Feng, Jianguo; Chen, Ying; Li, Shun; Ou, Mengting; Sun, Weichao; Tang, Liling

2017-01-31

Estradiol plays important roles in many biological responses inducing tumor genesis and cancer treatment. However, the effects of estradiol on tumors were inconsistent among a lot of researches and the mechanism is not fully understood. Our previous study indicated that splicing factor hnRNPA1 could bind to the human homologue of mouse double minute (MDM2), an oncogene which has been observed to be over-expressed in numerous types of cancers. In this research, we investigated whether and how estradiol correlate to cancer cell behaviors through heterogeneous nuclear ribonucleoprotein (hnRNPA1) and MDM2. Results showed that 10×10-13Mestradiol elevated the expression of hnRNPA1 regardless ER expression in cells, and then down-regulated the expression of MDM2. At the same time, estradiol inhibited cell proliferation, migration and epithelial-mesenchymal transition progression of A375 and GLL19 cells. While, knocking down hnRNPA1 through the transfection of hnRNPA1 siRNA led to the increase of MDM2 at both protein level and gene level In vivo experiment, subcutaneous injection with estradiol every two days near the tumor at doses of 2.5mg/kg/d suppressed tumor growth and reduced MDM2 expression. In a word, via increasing hnRNPA1 level and then reducing the expression of MDM2, estradiol prevented carcinogenesis in melanomas. We confirmed therapeutic effect of estradiol, as well as a new way for estradiol to resist skin cancer.

17β-Estradiol enhances sulforaphane cardioprotection against oxidative stress.

PubMed

Angeloni, Cristina; Teti, Gabriella; Barbalace, Maria Cristina; Malaguti, Marco; Falconi, Mirella; Hrelia, Silvana

2017-04-01

The lower incidence of ischemic heart disease in female with respect to male gender suggests the possibility that female sex hormones could have specific effects in cardiovascular protection. 17β-Estradiol is the predominant premenopausal circulating form of estrogen and has a protective role on the cardiovascular system. Recent evidences suggest that gender can influence the response to cardiovascular medications; therefore, we hypothesized that sex hormones could also modulate the cardioprotective effects of nutraceutical compounds, such as the isothiocyanate sulforaphane, present in Brassica vegetables. This study was designed to explore the protective effects of sulforaphane in the presence of 17β-estradiol against H 2 O 2 -induced oxidative stress in primary cultures of rat cardiomyocytes. Interestingly, 17β-estradiol enhanced sulforaphane protective activity against H 2 O 2 -induced cell death with respect to sulforaphane or 17β-estradiol alone as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl-tetrazolium bromide and lactate dehydrogenase assays. Moreover, 17β-estradiol boosted sulforaphane ability to counteract oxidative stress, reducing intracellular reactive oxygen species and 8-hydroxy-2'-deoxyguanosine levels and increasing the expression of phase II enzymes. Using specific antagonists of estrogen receptor α and β, we observed that these effects are not mediated by estrogen receptors. Otherwise, ERK1/2 and Akt signaling pathways seem to be involved, as the presence of specific inhibitors of these kinases reduced the protective effect of sulforaphane in the presence of 17β-estradiol. Sulforaphane and 17β-estradiol co-treatment counteracted cell morphology alterations induced by H 2 O 2 as evidenced by transmission electron microscopy. Our results demonstrated, for the first time, that estrogens could enhance sulforaphane protective effects, suggesting that nutraceutical efficacy might be modulated by sex hormones. Copyright © 2017 Elsevier

Estradiol targets T cell signaling pathways in human systemic lupus.

PubMed

Walters, Emily; Rider, Virginia; Abdou, Nabih I; Greenwell, Cindy; Svojanovsky, Stan; Smith, Peter; Kimler, Bruce F

2009-12-01

The major risk factor for developing systemic lupus erythematosus (SLE) is being female. The present study utilized gene profiles of activated T cells from females with SLE and healthy controls to identify signaling pathways uniquely regulated by estradiol that could contribute to SLE pathogenesis. Selected downstream pathway genes (+/- estradiol) were measured by real time polymerase chain amplification. Estradiol uniquely upregulated six pathways in SLE T cells that control T cell function including interferon-alpha signaling. Measurement of interferon-alpha pathway target gene expression revealed significant differences (p= 0.043) in DRIP150 (+/- estradiol) in SLE T cell samples while IFIT1 expression was bimodal and correlated moderately (r= 0.55) with disease activity. The results indicate that estradiol alters signaling pathways in activated SLE T cells that control T cell function. Differential expression of transcriptional coactivators could influence estrogen-dependent gene regulation in T cell signaling and contribute to SLE onset and disease pathogenesis.

Human Endometrial Adenocarcinoma Transplanted into Nude Mice: Growth Regulation by Estradiol

NASA Astrophysics Data System (ADS)

Satyaswaroop, P. G.; Zaino, R. J.; Mortel, R.

1983-01-01

A model for studying the growth of primary tumors of human endometrium and its regulation by 17β -estradiol has been developed in which ovariectomized nude mice are used as recipients. The receptors for sex steroids are maintained during serial transplantation of the tumor in this system. Although the rate of growth of receptor-negative endometrial tumors transplanted into ovariectomized nude mice is unaffected by the sustained presence or absence of estradiol, the growth of receptor-positive tumors is significantly increased by estradiol. Receptor-positive tumors treated with estradiol produced elevated concentrations of progesterone receptor. That the progesterone receptor is functional in this tumor is evident from the induction of estradiol 17β -dehydrogenase activity upon progestin administration. These findings are consistent with receptor-mediated regulation of growth of endometrial carcinoma.

Estradiol increases choice of cocaine over food in male rats.

PubMed

Bagley, Jared R; Adams, Julia; Bozadjian, Rachel V; Bubalo, Lana; Ploense, Kyle L; Kippin, Tod E

2017-10-19

Estradiol modulates the rewarding and reinforcing properties of cocaine in females, including an increase in selection of cocaine over alternative reinforcers. However, the effects of estradiol on male cocaine self-administration behavior are less studied despite equivalent levels of estradiol in the brains of adult males and females, estradiol effects on motivated behaviors in males that share underlying neural substrates with cocaine reinforcement as well as expression of estrogen receptors in the male brain. Therefore, we sought to characterize the effects of estradiol in males on choice between concurrently-available cocaine and food reinforcement as well as responding for cocaine or food in isolation. Male castrated rats (n=46) were treated daily with estradiol benzoate (EB) (5μg/0.1, S.C.) or vehicle (peanut oil) throughout operant acquisition of cocaine (1mg/kg, IV; FI20 sec) and food (3×45mg; FI20 sec) responding, choice during concurrent access and cocaine and food reinforcement under progressive ratio (PR) schedules. EB increased cocaine choice, both in terms of percent of trials on which cocaine was selected and the proportion of rats exhibiting a cocaine preference as well as increased cocaine, but not food, intake under PR. Additionally, within the EB treated group, cocaine-preferring rats exhibited enhanced acquisition of cocaine, but not food, reinforcement whereas no acquisition differences were observed across preferences in the vehicle treated group. These findings demonstrate that estradiol increases cocaine choice in males similarly to what is observed in females. Copyright © 2017 Elsevier Inc. All rights reserved.

Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel.

PubMed

Ahrendt, Hans-Joachim; Makalová, Dagmar; Parke, Susanne; Mellinger, Uwe; Mansour, Diana

2009-11-01

This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17beta-estradiol. This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years. Overall, 798 women were randomized and received allocated treatment (399 per group). There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [17.3+/-10.4 vs. 21.5+/-8.6, respectively, p<.0001, Reference Period 1 (Days 1-90); and 13.4+/-9.vs. 15.9+/-7.1, respectively, p<.0001, Reference Period 2 (Days 91-180)]. Through Cycles 1-7, the occurrence of scheduled withdrawal bleeding per cycle was 77.7-83.2% with E2V/DNG and 89.5-93.8% with EE/LNG (p<.0001 per cycle). The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5%-18.6%) and EE/LNG (9.9%-17.1%) (p>.05 per cycle). No unintended pregnancies occurred with E2V/DNG, but there was one unintended pregnancy with EE/LNG. Adverse drug reactions occurred in 10.0% and 8.5% of women taking E2V/DNG and EE/LNG, respectively. Overall, 79.4% of women were satisfied with E2V/DNG and 79.9% with EE/LNG. A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC.

Congener-specific extraction and separation of coplanar PCBs from soil using SPME and capillary GC/MS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woolley, C.L.; Mani, V.; Shirey, R.E.

1995-12-31

The persistence and widespread environmental occurrence of polychlorinated biphenyls (PCBs) in the air, waterways and industrial facilities has created a need for quantitative and qualitative analysis of Aroclor-like mixtures. Although there are 209 possible PCB concerns, only a limited number have shown toxic activity similar to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The World Health Organization recently released a list of the 13 most toxic PCB congeners. Each was rated by its Toxic Equivalency Factor relative to TCDD. These 13 PCB congeners belong to the class of toxic coplanar compounds. These congeners commonly contain chlorosubstitutions in the 3,3{prime},4,4{prime} or 3,4,4{prime} or 3{prime},4,4{prime} positions andmore » either 0, 1, or 2 chloro-substituents in the ortho positions. A new capillary column containing a bonded octylmethyl polysiloxane stationary phase (SPB-Octyl) was evaluated for its propensity to separate coplanar PCB congeners. Solid phase microextraction (SPME), a solvent-free method for extracting volatiles and semi-volatiles from drinking water, waste water, soil and sludge was used to extract PCBs from soil. GC-ECD and GC-MS separations of PCB ladened soils were examined via SPME on the SPB-Octyl column. An approach for selective extraction of coplanar PCB congeners by SPME will be described.« less

Levels and congener pattern of polychlorinated biphenyls in the blubber of the Mediterranean bottlenose dolphins Tursiops truncatus.

PubMed

Storelli, M M; Marcotrigiano, G O

2003-01-01

Isomer specific concentrations of individual polychlorinated biphenyls (PCBs) including toxic non-ortho (IUPAC 77, 126, 169) and mono-ortho (105, 118, 156) coplanar congeners were determined in the blubber of nine bottlenose dolphins (Tursiops truncatus) stranded along the Eastern Italian coast. The total PCB concentrations ranged from 3534 to 24375 ng/g wet wt. The PCB profile was dominated by congeners 138 and 153 collectively accounting for 55% of the total PCB concentrations. Among the most toxic congeners the order of abundance was 126>169>77. The mean total 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent of six coplanar PCBs in the blubber of bottlenose dolphins was 45596 pg/g. Non-ortho congeners contributed greater to the 2,3,7,8-TCDD toxic equivalents than mono-ortho members. Particularly, PCB 126 was the major contributor to the estimated toxic potency of PCBs in dolphins.

Estradiol selectively enhances auditory function in avian forebrain neurons

PubMed Central

Caras, Melissa L.; O’Brien, Matthew; Brenowitz, Eliot A.; Rubel, Edwin W

2012-01-01

Sex steroids modulate vertebrate sensory processing, but the impact of circulating hormone levels on forebrain function remains unclear. We tested the hypothesis that circulating sex steroids modulate single-unit responses in the avian telencephalic auditory nucleus, field L. We mimicked breeding or non-breeding conditions by manipulating plasma 17β-estradiol levels in wild-caught female Gambel’s white-crowned sparrows (Zonotrichia leucophrys gambelii). Extracellular responses of single neurons to tones and conspecific songs presented over a range of intensities revealed that estradiol selectively enhanced auditory function in cells that exhibited monotonic rate-level functions to pure tones. In these cells, estradiol treatment increased spontaneous and maximum evoked firing rates, increased pure tone response strengths and sensitivity, and expanded the range of intensities over which conspecific song stimuli elicited significant responses. Estradiol did not significantly alter the sensitivity or dynamic ranges of cells that exhibited non-monotonic rate-level functions. Notably, there was a robust correlation between plasma estradiol concentrations in individual birds and physiological response properties in monotonic, but not non-monotonic neurons. These findings demonstrate that functionally distinct classes of anatomically overlapping forebrain neurons are differentially regulated by sex steroid hormones in a dose-dependent manner. PMID:23223283

Dydrogesterone does not reverse the cardiovascular benefits of percutaneous estradiol.

PubMed

Kuba, V M; Teixeira, M A M; Meirelles, R M R; Assumpção, C R L; Costa, O S

2013-02-01

To evaluate the influence of dydrogesterone on estimated cardiovascular risk of users of hormone replacement therapy (HRT) (with percutaneous 17β-estradiol in monotherapy and in combination with dydrogesterone) and HRT non-users through the Framingham score tool for a period of 2 years. Framingham scores were calculated from the medical records of patients treated for at least 2 years with 17β-estradiol alone or in combination with dydrogesterone, along with HRT non-users, through the analysis of patient medical records, followed for at least 2 years at Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione. Improvements in lipid profile, glucose and blood pressure levels, which reduced the estimated cardiovascular risk, were observed in the 17β-estradiol group. Similar changes were observed in the users of 17β-estradiol + dydrogesterone, suggesting that this progestogen does not attenuate the effects caused by 17β-estradiol. Both HRT groups showed a reduction in their Framingham score. In contrast to data from other HRT investigations on cardiovascular risk, these formulations proved to be safe, even in the first year of use.

Stimulation of estradiol biosynthesis by tributyltin in rat hippocampal slices.

PubMed

Munetsuna, Eiji; Hattori, Minoru; Yamazaki, Takeshi

2014-01-01

Hippocampal functions are influenced by steroid hormones, such as testosterone and estradiol. It has been demonstrated that hippocampus-derived steroid hormones play important roles in neuronal protection and synapse formation. Our research groups have demonstrated that estradiol is de novo synthesized in the rat hippocampus. However, the mechanism(s) regulating this synthesis remains unclear. It has been reported that tributyltin, an environmental pollutant, binds to the retinoid X receptor (RXR) and modifies estrogen synthesis in human granulosa-like tumor cells. This compound can penetrate the blood brain barrier, and tends to accumulate in the brain. Based on these facts, we hypothesized that tributyltin could influence the hippocampal estradiol synthesis. A concentration of 0.1 μM tributyltin induced an increase in the mRNA content of P450(17α) and P450arom in hippocampal slices, as determined using real-time PCR. The transcript levels of other steroidogenic enzymes and a steroidogenic acute regulatory protein were not affected. The estradiol level in rat hippocampal slices was subsequently determined using a radioimmunoassay. We found that the estradiol synthesis was stimulated by ∼2-fold following a 48-h treatment with 0.1 μM tributyltin, and this was accompanied by transcriptional activation of P450(17α) and P450arom. Tributyltin stimulated de novo hippocampal estradiol synthesis by modifying the transcription of specific steroidogenic enzymes.

SEX, ESTRADIOL, AND SPATIAL MEMORY IN A FOOD-CACHING CORVID

PubMed Central

Rensel, Michelle A.; Ellis, Jesse M.S.; Harvey, Brigit; Schlinger, Barney A.

2015-01-01

Estrogens significantly impact spatial memory function in mammalian species. Songbirds express the estrogen synthetic enzyme aromatase at relatively high levels in the hippocampus and there is evidence from zebra finches that estrogens facilitate performance on spatial learning and/or memory tasks. It is unknown, however, whether estrogens influence hippocampal function in songbirds that naturally exhibit memory-intensive behaviors, such as cache recovery observed in many corvid species. To address this question, we examined the impact of estradiol on spatial memory in non-breeding Western scrub-jays, a species that routinely participates in food caching and retrieval in nature and in captivity. We also asked if there were sex differences in performance or responses to estradiol. Utilizing a combination of an aromatase inhibitor, fadrozole, with estradiol implants, we found that while overall cache recovery rates were unaffected by estradiol, several other indices of spatial memory, including searching efficiency and efficiency to retrieve the first item, were impaired in the presence of estradiol. In addition, males and females differed in some performance measures, although these differences appeared to be a consequence of the nature of the task as neither sex consistently out-performed the other. Overall, our data suggest that a sustained estradiol elevation in a food-caching bird impairs some, but not all, aspects of spatial memory on an innate behavioral task, at times in a sex-specific manner. PMID:26232613

Adsorption of Ten Microcystin Congeners to Common Laboratory-Ware Is Solvent and Surface Dependent.

PubMed

Altaner, Stefan; Puddick, Jonathan; Wood, Susanna A; Dietrich, Daniel R

2017-04-06

Cyanobacteria can produce heptapetides called microcystins (MC) which are harmful to humans due to their ability to inhibit cellular protein phosphatases. Quantitation of these toxins can be hampered by their adsorption to common laboratory-ware during sample processing and analysis. Because of their structural diversity (>100 congeners) and different physico-chemical properties, they vary in their adsorption to surfaces. In this study, the adsorption of ten different MC congeners (encompassing non-arginated to doubly-arginated congeners) to common laboratory-ware was assessed using different solvent combinations. Sample handling steps were mimicked with glass and polypropylene pipettes and vials with increasing methanol concentrations at two pH levels, before analysis by liquid chromatography-tandem mass spectrometry. We demonstrated that MC adsorb to polypropylene surfaces irrespective of pH. After eight successive pipet actions using polypropylene tips ca. 20% of the MC were lost to the surface material, which increased to 25%-40% when solutions were acidified. The observed loss was alleviated by changing the methanol (MeOH) concentration in the final solvent. The required MeOH concentration varied depending on which congener was present. Microcystins only adsorbed to glass pipettes (loss up to 30% after eight pipet actions) when in acidified aqueous solutions. The latter appeared largely dependent on the presence of ionizable groups, such as arginine residues.

Adsorption of Ten Microcystin Congeners to Common Laboratory-Ware Is Solvent and Surface Dependent

PubMed Central

Altaner, Stefan; Puddick, Jonathan; Wood, Susanna A.; Dietrich, Daniel R.

2017-01-01

Cyanobacteria can produce heptapetides called microcystins (MC) which are harmful to humans due to their ability to inhibit cellular protein phosphatases. Quantitation of these toxins can be hampered by their adsorption to common laboratory-ware during sample processing and analysis. Because of their structural diversity (>100 congeners) and different physico-chemical properties, they vary in their adsorption to surfaces. In this study, the adsorption of ten different MC congeners (encompassing non-arginated to doubly-arginated congeners) to common laboratory-ware was assessed using different solvent combinations. Sample handling steps were mimicked with glass and polypropylene pipettes and vials with increasing methanol concentrations at two pH levels, before analysis by liquid chromatography-tandem mass spectrometry. We demonstrated that MC adsorb to polypropylene surfaces irrespective of pH. After eight successive pipet actions using polypropylene tips ca. 20% of the MC were lost to the surface material, which increased to 25%–40% when solutions were acidified. The observed loss was alleviated by changing the methanol (MeOH) concentration in the final solvent. The required MeOH concentration varied depending on which congener was present. Microcystins only adsorbed to glass pipettes (loss up to 30% after eight pipet actions) when in acidified aqueous solutions. The latter appeared largely dependent on the presence of ionizable groups, such as arginine residues. PMID:28383495

Polychlorinated biphenyls in Great Lakes lake trout and their eggs: relations to survival and congener composition 1979-1988

USGS Publications Warehouse

Mac, Michael J.; Schwartz, Ted R.; Edsall, Carol C.; Frank, Anthony M.

1993-01-01

Eggs taken from lake trout (Salvelinus namaycush) captured from various Great Lakes between 1979 and 1988 were analyzed for individual polychlorinated biphenyl (PCB) congeners. Eggs from the same fish had been previously reared through hatching and early fry development to ascertain egg quality. Tissues from a subsample of the adult females that provided eggs were similarly analyzed. Significant relations were found between embryonic mortality (eggs dying between fertilization and hatch) and the concentrations of total PCBs in both the eggs and adults. PCB concentrations were also negatively correlated with the percentage of normal fry that successfully hatched, but no relation was found between PCB residues and fry mortality. Pattern recognition analysis indicated that the PCB congener fingerprint for eggs from Lake Superior was different than that of eggs from Lakes Michigan, Huron, and Ontario. A difference between PCB residue patterns was also identified between eggs and the parent fish. While this difference indicated some preferential deposition of congeners in the eggs, the difference was not attributed to the toxic AHH-active congeners. No difference in the PCB pattern was observed over the 10 years of sample collection, demonstrating that concentrations of individual congeners are declining at similar rates.

CONGENER-SPECIFIC DETECTION OF DIOXINS USING JET-REMPI. (R827927)

EPA Science Inventory

Although 210 chemically different polychlorinated dibenzo-p-dioxin and dibenzofuran congeners can be produced during combustion, it is currently believed that fewer than 20 are toxic enough to warrant monitoring. SRI is developing a continuous emissions monitor to study...

Dissipation of 17B-estradiol in composted poultry litter

USDA-ARS?s Scientific Manuscript database

The effects of heated composting and ambient temperature poultry waste decomposition on the fate of 17ß-estradiol and testosterone were determined in separate experiments. A mixture of poultry litter, wood chips and straw was amended with [14C]17ß-estradiol or [14C]testosterone and allowed to under...

Hepatocyte transplantation for enzyme deficiency disease in congenic rats.

PubMed

Vroemen, J P; Buurman, W A; Heirwegh, K P; van der Linden, C J; Kootstra, G

1986-08-01

Long-term effects of hepatocyte transplantation (HTX) in the treatment of enzyme deficiency disease were studied. Congenic enzyme-deficient (R/APfd-j/j) and non-enzyme-deficient (R/APfd) rats were used as recipients and donors, respectively. The R/APfd-j/j rat strain is congenitally deficient of bilirubin uridyldiphosphate (UDP)-glucuronyl transferase. R/APfd-j/j rats underwent HTX by intrasplenic injection of 10(7) isolated R/APfd hepatocytes (group 1A). Another group of R/APfd-j/j rats was treated similarly, but underwent splenectomy after 11 weeks (group 1B). Controls consisted of R/APfd-j/j rats grafted with 10(7) R/APfd-j/j hepatocytes (group 2), and R/APfd-j/j rats that underwent a sham operation (group 3). Total plasma bilirubin (TB) levels were significantly reduced in groups 1A and 1B during the experiment (both P less than 0.01). In the control groups TB reduction was not observed. Bile analyses at 30 weeks after HTX showed that in group 1A 13.7 +/- 2.7% of total biliary bilirubin was conjugated. In group 1B a significantly lower fraction was conjugated: 6.6 +/- 1.1% (P less than 0.05). Conjugated bilirubin was not found in bile of groups 2 and 3. Histology showed survival of hepatocytes in all spleens of rats of groups 1A, 1B and 2. It is concluded that congenic hepatocytes from R/APfd donors are not rejected after transplantation into the R/APfd-j/j rat, and maintain long-term function. Splenectomy does not abolish, but does reduce, the therapeutic effect significantly, indicating that part of the transplanted hepatocytes maintains function in the enzyme-deficient host liver. The congenic R/APfd-j/j and R/APfd rat strains represent a new animal model for research in metabolic deficiency disease.

Sex, estradiol, and spatial memory in a food-caching corvid.

PubMed

Rensel, Michelle A; Ellis, Jesse M S; Harvey, Brigit; Schlinger, Barney A

2015-09-01

Estrogens significantly impact spatial memory function in mammalian species. Songbirds express the estrogen synthetic enzyme aromatase at relatively high levels in the hippocampus and there is evidence from zebra finches that estrogens facilitate performance on spatial learning and/or memory tasks. It is unknown, however, whether estrogens influence hippocampal function in songbirds that naturally exhibit memory-intensive behaviors, such as cache recovery observed in many corvid species. To address this question, we examined the impact of estradiol on spatial memory in non-breeding Western scrub-jays, a species that routinely participates in food caching and retrieval in nature and in captivity. We also asked if there were sex differences in performance or responses to estradiol. Utilizing a combination of an aromatase inhibitor, fadrozole, with estradiol implants, we found that while overall cache recovery rates were unaffected by estradiol, several other indices of spatial memory, including searching efficiency and efficiency to retrieve the first item, were impaired in the presence of estradiol. In addition, males and females differed in some performance measures, although these differences appeared to be a consequence of the nature of the task as neither sex consistently out-performed the other. Overall, our data suggest that a sustained estradiol elevation in a food-caching bird impairs some, but not all, aspects of spatial memory on an innate behavioral task, at times in a sex-specific manner. Copyright © 2015 Elsevier Inc. All rights reserved.

Disposition of toxic PCB congeners in snapping turtle eggs: expressed as toxic equivalents of TCDD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bryan, A.M.; Stone, W.B.; Olafsson, P.G.

1987-11-01

Studies of snapping turtles, taken from the region of the Upper Hudson River, in New York State, revealed exceedingly high levels of PCBs in the adipose tissue. There is evidence to suggest that large reserves of fat provide protection against chlorinated hydrocarbon toxicity. Such storage may protect snapping turtle eggs from disposition of toxic PCB congeners and account for the apparent absence of reports regarding detrimental effects on the hatchability of eggs from turtles living in the vicinity of the upper Hudson River. The present study was undertaken to determine if indeed these eggs are protected against disposition of toxicmore » PCB congeners by the presence of large reserves of fat. Although tissue volumes play an important role in determining the initial site of disposition, the major factor controlling the elimination of these compounds involves metabolism. For simple halogenated benzenes as well as for more complex halogenated biphenyls, oxidative metabolism catalyzed by P-448, occurs primarily at the site of two adjacent unsubstituted carbon atoms via arene oxide formation leading to the formation of water soluble metabolites. Toxicological studies have demonstrated that the most toxic PCB congeners, isosteriomers of tetrachlorodibenzo-p-dioxin (TCDD), require no metabolic activation. These compounds have chlorine atoms in the meta and para positions of both rings. It may be concluded that the structures of PCB congeners and isomers which favor induction of cytochrome P-448 are also those which are toxic and resist metabolism. It is the objective of the present study to determine if the heavy fat bodies of the female turtle provide a sufficiently large sink to retain the toxic congeners and prevent their incorporation into the eggs.« less

Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women

NASA Technical Reports Server (NTRS)

Ettinger, B.; Genant, H. K.; Steiger, P.; Madvig, P.

1992-01-01

With the use of a double-blind, randomized, dose-ranging design, we tested during an 18-month period the degree of protection against postmenopausal bone loss afforded by micronized 17 beta-estradiol in dosages of 0.5, 1.0, and 2.0 mg. All subjects received supplementation to ensure a minimum of 1500 mg calcium daily. Fifty-one subjects completed at least 1 year of follow-up bone density measurements by quantitative computed tomography and by single- and dual-photon absorptiometry. In the placebo group spinal trabecular bone density decreased 4.9% annually (p less than 0.001), whereas in those taking micronized 17 beta-estradiol bone density tended to increase (annual increases of 0.3% in the 0.5 mg micronized 17 beta-estradiol group, 1.8% in the 1.0 mg micronized 17 beta-estradiol group, and 2.5% in the 2.0 mg micronized 17 beta-estradiol group). After completing the double-blind phase, 41 subjects completed an additional 18 months of follow-up while taking 1.0 mg micronized 17 beta-estradiol. During this time one third of the subjects were randomly assigned to discontinue calcium supplements. Among those who previously received placebo, trabecular bone density increased 4.3% annually, whereas among those who had used micronized 17 beta-estradiol, trabecular bone density response was inversely related to the dosage previously used. Additionally and independently, the level of calcium intake showed a statistically significant correlation with the change in spinal trabecular bone density (r = 0.37, p = 0.02). We conclude that micronized 17 beta-estradiol has a continuous skeletal dose-response effect in the range of 0.5 to 2.0 mg and that calcium intake positively modifies the skeletal response to 1.0 mg micronized 17 beta-estradiol.

Laser spectroscopic study of β-estradiol and its monohydrated clusters in a supersonic jet.

PubMed

Morishima, Fumiya; Inokuchi, Yoshiya; Ebata, Takayuki

2012-08-09

The structures of 17β-estradiol (estradiol) and its 1:1 cluster with water have been investigated in supersonic jets. The S(1)-S(0) electronic spectrum of estradiol monomer shows four strong sharp bands in the 35050-35200 cm(-1) region. Ultraviolet-ultraviolet hole-burning (UV-UV HB) and infrared-ultraviolet double-resonance (IR-UV DR) spectra of these bands indicate that they are due to four different conformers of estradiol originating from the different orientation of the OH groups in the A- and D-rings. The addition of water vapor to the sample gas generates four new bands in the 34700-34800 cm(-1) region, which are assigned to the estradiol-H(2)O 1:1 cluster with the A-ring (phenyl ring) OH acting as a hydrogen(H)-bond donor. In addition, we found very weak bands near the origin bands of bare estradiol upon the addition of water vapor. These bands are assigned to the isomers of estradiol-H(2)O 1:1 cluster having an H-bond at the D-ring OH. We determine the conformation of bare estradiol and the structures of its monohydrated clusters with the aid of density functional theory calculation and discuss the relationship between the stability of hydrated clusters and the conformation of estradiol.

Geographic variation of PCB congeners in polar bears (Ursus maritimus) from Svalbard east to the Chukchi Sea

USGS Publications Warehouse

Andersen, M.; Lie, E.; Derocher, A.E.; Belikov, S.E.; Bernhoft, A.; Boltunov, Andrei N.; Garner, G.W.; Skaare, J.U.; Wiig, Øystein

2001-01-01

We present data on geographic variation in polychlorinated biphenyl (PCB) congeners in adult female polar bears (Ursus maritimus) from Svalbard eastward to the Chukchi Sea. Blood samples from 90 free-living polar bears were collected in 1987–1995. Six PCB congeners, penta to octa chlorinated (PCB-99, -118, -153, -156, -180, -194), were selected for this study. Differences between areas were found in PCB levels and congener patterns. Bears from Franz Josef Land (11,194 ng/g lipid weight) and the Kara Sea (9,412 ng/g lw) had similar ΣPCB levels and were higher than all other populations (Svalbard 5,043 ng/g lw, East Siberian Sea 3,564 ng/g lw, Chukchi Sea 2,465 ng/g lw). Svalbard PCB levels were higher than those from the Chukchi Sea. Our results, combined with earlier findings, indicate that polar bears from Franz Josef Land and the Kara Sea have the highest PCB levels in the Arctic. Decreasing trends were seen eastwards and westwards from this region. Of the congeners investigated in the present study, the lower chlorinated PCBs are increasing and the high chlorinated PCBs are decreasing from Svalbard eastward to the Chukchi Sea. Different pollution sources, compound transport patterns and regional prey differences could explain the variation in PCB congener levels and patterns between regions.

The Effect of Estradiol on the Growth Plate Chondrocytes of Limb and Spine from Postnatal Mice in vitro: The Role of Estrogen-Receptor and Estradiol Concentration.

PubMed

Shi, Sheng; Zheng, Shuang; Li, Xin-Feng; Liu, Zu-De

2017-01-01

Objectives: Skeletal development is a complex process. Little is known about the different response of limb or spine growth plate chondrocytes (LGP or SGP) to the estrogen level and the role of estrogen receptor (ER) during postnatal stage. Methods: LGP and SGP chondrocytes were isolated from 50 one-week mice and treated with different concentrations of 17β-estradiol. Cell viability was measured by cell counting kit-8 (CCK-8). The expression of collagen II and X were evaluated by real-time PCR and Western blotting. Then, the response of LGP or SGP chondrocyte after with or without estradiol and specific ER antagonists to block the effect of ERs were also measured by Western blotting and immunofluorescence. Results: Estradiol promoted the chondrogensis of the chondrocytes in vitro and achieved the maximal expression of type II collagen at the dose of 10 -7 M. Additionally, the regulatory effect of estradiol on the chondrogenesis can be mainly relied on ERα. The LGP chondrocytes were more sensitive to the estradiol treatment than SGP in the expression of type II collagen. Conclusions: Estrogen at a pharmacological concentration (10 -7 M) could stimulate the maximal production of type II collagen in the growth plate chondrocytes in vitro, which exerts its activity mainly through ERα in the chondrogenesis. Furthermore, the LGP chondrocytes were more sensitive to the estradiol treatment than SGP in the chondrogenesis.

PCB congener patterns in rats consuming diets containing Great Lakes salmon: Analysis of fish, diets, and adipose tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jordan, S.A.; Feeley, M.M.

1999-02-01

As part of a multidisciplinary toxicological investigation into Great Lakes contaminants, chinook salmon were collected from lake Huron (LH) and Lake Ontario (LO) and incorporated into standard rat diets as 20 or 100% of the protein complement. Final PCB concentrations in the experiment ranged from 3.15 ng/g in the control diet to 1,080 ngg in the high-dose LO diet, with maximal estimated daily consumption by the rats of 82 {micro}g PCBs/kg body wt in the LO20 dietary group. Seventeen PCB congeners, PCB 85, 99, 101, 105, 110, 118, 128, 129, 132, 138, 149, 153, 170, 177, 180, 187, and 199,more » occurred at > 3.0% of the total PCBs in the fish with no major site differences. Cumulatively, these 17 congeners accounted for up to 75% of the total PCBs in the fish compared to 44 and 54% in two commercial Aroclors, 1254 and 1260, respectively. PCB 77 was the major dioxin-like congener in the fish, followed by PCB 126 and then PCB 169. All major dietary congeners bioaccumulated in the adipose tissue of the rats with the exception of PCB congeners 101, 110, 132, and 149.« less

Quantifying Short-Chain Chlorinated Paraffin Congener Groups.

PubMed

Yuan, Bo; Bogdal, Christian; Berger, Urs; MacLeod, Matthew; Gebbink, Wouter A; Alsberg, Tomas; de Wit, Cynthia A

2017-09-19

Accurate quantification of short-chain chlorinated paraffins (SCCPs) poses an exceptional challenge to analytical chemists. SCCPs are complex mixtures of chlorinated alkanes with variable chain length and chlorination level; congeners with a fixed chain length (n) and number of chlorines (m) are referred to as a "congener group" C n Cl m . Recently, we resolved individual C n Cl m by mathematically deconvolving soft ionization high-resolution mass spectra of SCCP mixtures. Here we extend the method to quantifying C n Cl m by introducing C n Cl m specific response factors (RFs) that are calculated from 17 SCCP chain-length standards with a single carbon chain length and variable chlorination level. The signal pattern of each standard is measured on APCI-QTOF-MS. RFs of each C n Cl m are obtained by pairwise optimization of the normal distribution's fit to the signal patterns of the 17 chain-length standards. The method was verified by quantifying SCCP technical mixtures and spiked environmental samples with accuracies of 82-123% and 76-109%, respectively. The absolute differences between calculated and manufacturer-reported chlorination degrees were -0.9 to 1.0%Cl for SCCP mixtures of 49-71%Cl. The quantification method has been replicated with ECNI magnetic sector MS and ECNI-Q-Orbitrap-MS. C n Cl m concentrations determined with the three instruments were highly correlated (R 2 > 0.90) with each other.

Rcan2 and estradiol independently regulate body weight in female mice

PubMed Central

Ding, Ling-Cui; Gong, Qian-Qian; Li, Shi-Wei; Fu, Xiao-Long; Jin, Ye-Cheng; Zhang, Jian; Gao, Jian-Gang; Sun, Xiao-Yang

2017-01-01

Rcan2 increases food intake and plays an important role in the development of age- and diet- induced obesity in male mice. However, in females, wild-type mice grow almost at a similar rate as Rcan2−/− mice on normal chow diet from 6 weeks of age. Here we showed that the ability of Rcan2 to promote weight gain was attenuated by energy expenditure mediated by 17β-estradiol in female mice. Using ovariectomy-operated models, we found that 17β-estradiol deprivation did not alter food intake, but induced more weight gain in wild-type mice than Rcan2−/− mice. If wild-type mice ingested equally as Rcan2−/− mice, in the same ovarian state they exhibited similar weight changes, but the mice in ovariectomized groups were significantly heavier than the ovarian-intact mice, suggesting that body weight is not only regulated by Rcan2, but also by 17β-estradiol. Furthermore, we demonstrated that Rcan2 and 17β-estradiol independently regulated body weight even on high-fat diets. Therefore, our findings indicate that Rcan2 and 17β-estradiol regulate body weight through different mechanisms. Rcan2 increases food intake, whereas 17β-estradiol promotes energy expenditure. These findings provide novel insights into the sexual dimorphism of body weight regulation. PMID:28624805

Association Between Preovulatory Concentrations of Estradiol and Expression of Uterine Milk Protein Precursor, Inhibin Beta A, Period 1, Proenkephalin, and Receptors for Oxytocin, Progesterone, and Estradiol

USDA-ARS?s Scientific Manuscript database

Eliminating the preovulatory surge of estradiol decreased uterine weight, uterine protein, RNA to DNA ratio, rate of protein synthesis, and embryo survival following embryo transfer in sheep. Furthermore, cows that did not exhibit standing estrus (decreased preovulatory concentrations of estradiol) ...

New estradiol-linked nitrosoureas: can the pharmacokinetic properties help to explain the pharmacodynamic activities?

PubMed

Betsch, B; Berger, M R; Spiegelhalder, B; Eisenbrand, G; Schmähl, D

1989-01-01

The pharmacokinetics of 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine-estradiol-17-ester (CNC-alanine-estradiol-17-ester) a new estradiol-linked anticancer drug and the unlinked DNA-crosslinking agent 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine (CNC-alanine) have been studied in methylnitrosourea-induced female Sprague-Dawley rats after equimolar intravenous and oral administration. In comparison with the unlinked single agent, the CNC-alanine-estradiol-17-ester showed a 3-fold longer halflife in plasma and a three times larger volume of distribution. The distribution after intravenous administration was nearly three times faster. The absorption after peroral administration was likewise two times faster. The bioavailability of the estradiol-linked drug was determined to be 52%. After application of CNC-alanine-estradiol-17-ester the cytostatic metabolite CNC-alanine was found, indicating the cleavage of the ester bond. CNC-alanine generated from CNC-alanine-estradiol-17-ester showed a 50% longer halflife than when applied directly. The results indicate that linking 2-chloroethyl-nitrosoureas to estradiol can result in new anticancer agents with modified properties in comparison to the unlinked single agent. The higher antineoplastic activity of the hormone-linked drug can mainly be attributed to differences in the pharmacokinetic behaviour.

Estradiol and progesterone influence on influenza infection and immune response in a mouse model.

PubMed

Davis, Sarah M; Sweet, Leigh M; Oppenheimer, Karen H; Suratt, Benjamin T; Phillippe, Mark

2017-10-01

Influenza infection severity may be mediated by estradiol and/or progesterone. An exploratory study was designed to evaluate 17-β-estradiol and progesterone on influenza infection and examine immune-mediated response in a mouse model. Inoculation with placebo or mouse-adapted H1N1 influenza virus occurred. Treatment groups included 17-β-estradiol, progesterone, ovariectomy, and pregnancy. Mice were assessed for morbidity and mortality. Toll-like receptor gene studies and airspace cell differentials were performed. Onset of morbidity was earlier and morbidity duration greater for progesterone. Absence of morbidity/mortality and overall survival was greater for 17-β-estradiol. Airspace cell differentials suggest improved immune cell recruitment for 17-β-estradiol. Pregnant mouse data demonstrate significant mortality during the period of increased progesterone. Select immune cell markers demonstrate patterns of regulation that may promote proper immune response to influenza infection for 17-β-estradiol. Estradiol may play a protective and progesterone a detrimental role in the pathophysiology of influenza infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of estradiol and FSH on leptin levels in women with suppressed pituitary.

PubMed

Geber, Selmo; Brandão, Augusto H F; Sampaio, Marcos

2012-06-15

Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student's t-test and Pearson's correlation test. We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH.

Leptin Signaling Is Not Required for Anorexigenic Estradiol Effects in Female Mice.

PubMed

Kim, Joon S; Rizwan, Mohammed Z; Clegg, Deborah J; Anderson, Greg M

2016-05-01

Estradiol and leptin are critical hormones in the regulation of body weight. The aim of this study was to determine whether this cross talk between leptin receptor (LepRb) and estrogen receptor-α (ERα) signaling is critical for estradiol's anorexigenic effects. Leprb-Cre mice were crossed with Cre-dependent Tau-green fluorescent protein (GFP) reporter, Stat3-flox or Erα-flox mice to generate female mice with GFP expression, signal transducer and activator of transcription 3 (STAT3) knockout (KO), or ERα KO, specifically in LepRb-expressing cells. The proportion of Leprb-GFP cells colocalizing ERα was high (∼80%) in the preoptic area but low (∼10%) in the mediobasal hypothalamus, suggesting that intracellular cross talk between these receptors is minimal for metabolic regulation. To test whether estradiol enhanced arcuate leptin sensitivity, ovarectomized mice received varying levels of estradiol replacement. Increasing estrogenic states did not increase the degree of leptin-induced STAT3 phosphorylation. LepRb-specific STAT3 KO mice and controls were ovarectomized and given either chronic estradiol or vehicle treatment to test whether STAT3 is required for estrogen-induced body weight suppression. Both groups of estradiol-treated mice showed an equivalent reduction in body weight and fat content compared with vehicle controls. Finally, mice lacking ERα specifically in LepRb-expressing neurons also showed no increase in body weight or impairments in metabolic function compared with controls, indicating that estradiol acts independently of leptin-responsive cells to regulate body weight. However, fecundity was impaired in in Leprb-ERα KO females. Contrary to the current dogma, we report that estradiol has minimal direct actions on LepRb cells in the mediodasal hypothalamus and that its anorexigenic effects can occur entirely independently of LepRb-STAT3 signaling in female mice.

A metabolomics study of the inhibitory effect of 17-beta-estradiol on osteoclast proliferation and differentiation.

PubMed

Liu, Xiaoyan; Liu, Yanqiu; Cheng, Mengchun; Zhang, Xiaozhe; Xiao, Hongbin

2015-02-01

Estradiol is a major drug used clinically to alleviate osteoporosis, partly through inhibition of the activity of osteoclasts, which play a crucial role in bone resorption. So far, little is known about the effects of estradiol on osteoclast metabolism. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC/MS)-based metabolomics strategy was used to investigate the metabolite response to 17β-estradiol in mouse osteoclast RAW264.7, a commonly used cell model for studying osteoporosis. Our results showed that the application of estradiol altered the levels of 27 intracellular metabolites, including lysophosphatidylcholines (LysoPCs), other lipids and amino acid derivants. The changes of all the 27 metabolites were observed in the study of estradiol induced osteoclast proliferation inhibition (1 μM estradiol applied), while the changes of only 18 metabolites were observed in the study of differentiation inhibition (0.1 μM estradiol applied). Further pathway impact analysis determined glycerophospholipid metabolism as the main potential target pathway of estradiol, which was further confirmed by LCAT (phosphatidylcholine-sterol acyltransferase) activity changes and lipid peroxidative product (MDA, methane dicarboxylic aldehyde) changes caused by estradiol. Additionally, we found that estradiol significantly decreased intracellular oxidative stress during cell proliferation but not during cell differentiation. Our study suggested that estradiol generated a highly condition-dependent influence on osteoclast metabolism.

Estradiol or fluoxetine alters depressive behavior and tryptophan hydroxylase in rat raphe.

PubMed

Yang, Fu-Zhong; Wu, Yan; Zhang, Wei-Guo; Cai, Yi-Yun; Shi, Shen-Xun

2010-03-10

The effects of 17beta-estradiol and fluoxetine on behavior of ovariectomized rats subjected to the forced swimming test and the expression of tryptophan hydroxylase (TPH) in dorsal and median raphe were investigated, respectively through time sampling technique of behavior scoring and immunohistochemistry. Both estradiol and fluoxetine increased swimming and decreased immobility in the forced swimming test. The forced swimming stress decreased integrated optical density of TPH-positive regions in dorsal and median raphe. Both estradiol and fluoxetine administration prevented integrated optical density of TPH-positive regions from being decreased by forced swimming stress. These observations suggest that both estradiol and fluoxetine have protective bearing on ovariectomized rats enduring forced swimming stress.

ANALYSIS OF CHIRAL PESTICIDES AND POLYCHLORINATED BIPHENYL CONGENERS IN ENVIRONMENTAL SAMPLES

EPA Science Inventory

Over 25 % of pesticides and other toxic organic pollutants are chiral, as are 19 of the 209 polychlorinated biphenyl (PCB) congeners; that is, they exist as two mirror image species called enantiomers (PCB enantiomers are called atropisomers). The enantiomers of a chiral compound...

Endothelial function across an oral contraceptive cycle in women using levonorgestrel and ethinyl estradiol.

PubMed

Torgrimson, Britta N; Meendering, Jessica R; Kaplan, Paul F; Minson, Christopher T

2007-06-01

Oral contraceptive pills (OCPs) are a popular contraception method. Currently, lower-dose ethinyl estradiol formulations are most commonly prescribed, although they have been linked to increased arterial vascular risk. The aim of this study was to investigate endothelial function in healthy young women using lower-dose ethinyl estradiol OCPs. We examined flow-mediated, endothelium-dependent and nitroglycerin-mediated, endothelium-independent vasodilation of the brachial artery, comparing two doses of ethinyl estradiol/levonorgestrel OCPs in 15 healthy young women on two study days: once during the active phase and once during the placebo phase of an OCP cycle. Group low dose (LD) (n=7) active pills contained 150 microg levonorgestrel/30 microg ethinyl estradiol versus Group very low dose (VLD) (n=8) with 100 microg levonorgestrel/20 microg ethinyl estradiol. Endothelium-dependent vasodilation was lower during the active phase in Group VLD (5.33 +/- 1.77% vs. 7.23 +/- 2.60%; P=0.024). This phase difference was not observed in Group LD (8.00 +/- 0.970% vs. 7.61 +/- 1.07%; P=0.647). Endothelium-independent vasodilation did not differ between phases in either group. Finally, we measured endothelium-dependent vasodilation in two additional women who received 10 microg of unopposed ethinyl estradiol. Endothelium-dependent vasodilation was increased by unopposed ethinyl estradiol compared with the placebo phase (10.88 +/- 2.34% vs. 6.97 +/- 1.83%). These results suggest that levonorgestrel may antagonize the activity of ethinyl estradiol. Thus both the progestin type and estradiol dose need to be considered when assessing arterial vascular risk of OCP use in women.

A multicenter randomized comparison of cycle control and laboratory findings with oral contraceptive agents containing 100 microg levonorgestrel with 20 microg ethinyl estradiol or triphasic norethindrone with ethinyl estradiol.

PubMed

Reisman, H; Martin, D; Gast, M J

1999-11-01

This study was undertaken to compare the effects of 2 oral contraceptive regimens on menstrual cycle control and laboratory findings. In a multicenter randomized study 100 microg levonorgestrel with 20 microg ethinyl estradiol (Alesse or Loette) was given to 155 healthy women. A triphasic preparation of 500, 750, and 1000 microg norethindrone with 35 microg ethinyl estradiol (Ortho-Novum 7/7/7 or TriNovum) was given to 167 women for 1 to 4 cycles of treatment. Overall, the percentages of normal menstrual cycles and the percentages of cycles with intermenstrual and withdrawal bleeding were similar between the 2 treatment groups. In the levonorgestrel with ethinyl estradiol group, there was a statistically significantly longer latent period and a statistically significantly shorter withdrawal bleeding episode. Adverse events were similar between treatment groups, and none were serious. Most mean changes from baseline laboratory values were comparable between groups, although the mean increase in cholesterol concentration was statistically significantly lower in the levonorgestrel with ethinyl estradiol group. Changes in triglyceride and glucose concentrations were not statistically significantly different between groups. Levonorgestrel (100 microg) with ethinyl estradiol (20 microg) provides menstrual cycle control equivalent to that obtained with triphasic norethindrone with ethinyl estradiol (75% higher estrogen dose) with similar safety and tolerability.

Trait responses of invasive aquatic macrophyte congeners: colonizing diploid outperforms polyploid

USDA-ARS?s Scientific Manuscript database

Understanding traits underlying colonization and niche breadth of invasive plants is key to developing sustainable management solutions to curtail invasions at the establishment phase, when efforts are often most effective. The aim of this study was to evaluate how two invasive congeners differing i...

L-Type Calcium Channels Modulation by Estradiol.

PubMed

Vega-Vela, Nelson E; Osorio, Daniel; Avila-Rodriguez, Marco; Gonzalez, Janneth; García-Segura, Luis Miguel; Echeverria, Valentina; Barreto, George E

2017-09-01

Voltage-gated calcium channels are key regulators of brain function, and their dysfunction has been associated with multiple conditions and neurodegenerative diseases because they couple membrane depolarization to the influx of calcium-and other processes such as gene expression-in excitable cells. L-type calcium channels, one of the three major classes and probably the best characterized of the voltage-gated calcium channels, act as an essential calcium binding proteins with a significant biological relevance. It is well known that estradiol can activate rapidly brain signaling pathways and modulatory/regulatory proteins through non-genomic (or non-transcriptional) mechanisms, which lead to an increase of intracellular calcium that activate multiple kinases and signaling cascades, in the same way as L-type calcium channels responses. In this context, estrogens-L-type calcium channels signaling raises intracellular calcium levels and activates the same signaling cascades in the brain probably through estrogen receptor-independent modulatory mechanisms. In this review, we discuss the available literature on this area, which seems to suggest that estradiol exerts dual effects/modulation on these channels in a concentration-dependent manner (as a potentiator of these channels in pM concentrations and as an inhibitor in nM concentrations). Indeed, estradiol may orchestrate multiple neurotrophic responses, which open a new avenue for the development of novel estrogen-based therapies to alleviate different neuropathologies. We also highlight that it is essential to determine through computational and/or experimental approaches the interaction between estradiol and L-type calcium channels to assist these developments, which is an interesting area of research that deserves a closer look in future biomedical research.

Effects of estradiol and FSH on leptin levels in women with suppressed pituitary

PubMed Central

2012-01-01

Background Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. Methods A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student’s t-test and Pearson’s correlation test. Results We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. Conclusions This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH. PMID:22703959

Influence of estradiol and androstenedione on ACTH and cortisol secretion in the ovine fetus.

PubMed

Wood, C E; Saoud, C J

1997-01-01

To test the hypothesis that physiologic increases in fetal plasma 17 beta-estradiol and androstenedione modulate the activity of the fetal hypothalamic-pituitary-adrenal (HPA) axis. Seventeen pregnant ewes and their fetuses were chronically catheterized. At the time of surgery, the fetuses received implants that released 17 beta-estradiol (n = 5) alone or 17 beta-estradiol and androstenedione (n = 6), each at a rate of approximately 250 micrograms/day for each steroid. The control group (n = 6) received either no pellet (n = 2) or a "placebo" pellet, which contained no steroid (n = 4). Fetal blood samples were drawn for hormone and blood gas analysis at 1-3-day intervals until the time of spontaneous parturition. Fetal plasma ACTH and cortisol concentrations were fit to semilogarithmic equations and analyzed by stepwise multiple linear regression analysis for statistically significant effects of 17 beta-estradiol and androstenedione. Estradiol significantly increased and androstenedione significantly decreased the ACTH and cortisol concentrations. Treatment with both 17 beta-estradiol and androstenedione resulted in parturition approximately 4 days earlier than in the other groups (P < .05). Physiologic increases in fetal plasma estradiol and androstenedione modify the activity of the HPA axis.

Role of an estradiol regulatory factor-hydroxysteroid dehydrogenase (HSD) in Toxoplasma gondii infection and pathogenicity.

PubMed

Zhang, Xiao; Liu, Jing; Li, Muzi; Fu, Yong; Zhang, Taotao; Han, Qian; Liu, Qun

2017-11-01

Toxoplasma gondii is an apicomplexan parasite that infects most species of warm-blooded animals, including humans, and causes abortions and severe damage to the fetal central nervous system. During pregnancy, the prevalence of toxoplasmosis increases throughout the second and third quarter of gestation, while the hormones progesterone and estradiol simultaneously increase. Thus, it has been suggested that these hormones could affect parasite reproduction. This study was mainly focused on an estradiol regulatory factor-Hydroxysteroid dehydrogenase (HSD) gene in T. gondii. Our data showed that estradiol promoted Pru (Type II) and VEG (Type III) infection and thus significantly contributed to the pathogenicity of T. gondii in mice. Subsequently, we found that this phenomenon may relate to the interplay of T. gondii and estradiol. We reported that estradiol can enter T. gondii tachyzoites. Bioinformatics analysis showed that T. gondii may have a residual estradiol metabolism-related gene HSD. To verify the gene function, HEK293T cells were transiently transfected with Tg-HSD and gene expression was induced. Then, HPLC (high-performance liquid chromatography) analysis showed that Tg-HSD can efficiently transform estrone into estradiol. Moreover, Tg-HSD -overexpressing parasites showed significantly enhanced pathogenicity and upregulation of estradiol levels in mice. In conclusion, estradiol can promote T. gondii infection in vitro and in vivo, and this may be related to its Tg- HSD gene. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relationship between ovarian reserve and preovulatory estradiol during a fixed-time AI protocol in beef heifers

USDA-ARS?s Scientific Manuscript database

Estradiol production is essential for reproductive efficiency. This study compared numbers of follicles in beef cows that did or did not have elevated preovulatory estradiol during a fixed-time AI (FTAI) protocol. In experiment 1, 5 low estradiol (LowE2) and 5 high estradiol (HighE2) cows were slaug...

ESTIMATING SYSTEMIC EXPOSURE TO ETHINYL ESTRADIOL FROM AN ORAL CONTRACEPTIVE

PubMed Central

WESTHOFF, Carolyn L.; PIKE, Malcolm C.; TANG, Rosalind; DINAPOLI, Marianne N.; SULL, Monica; CREMERS, Serge

2015-01-01

Objectives This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive to steady-state values, and to assess whether any simpler measures could provide an adequate proxy of the ‘gold standard’ 24-hour steady-state area-under-the-curve. Identifying a simple, less expensive, measure of systemic ethinyl estradiol exposure would be useful for larger studies designed to assess the relationship between an individual’s ethinyl estradiol exposure and her side effects. Study Design We conducted a 13 samples over 24 hours pharmacokinetic analysis on day 1 and day 21 of the first cycle of a monophasic oral contraceptive containing 30 mcg ethinyl estradiol and 150 mcg levonorgestrel in 17 non-obese healthy white women. We also conducted an abbreviated single dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of full 13-sample steady-state pharmacokinetic analysis with results calculated using fewer samples (9 or 5) and following the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. Results The area-under-the-curve, maximum (Cmax), and 24-hour (C24) values were similar following the two single oral contraceptive doses (area-under-the-curve, r = 0.92). The steady-state 13-sample 24-hour area-under-the-curve was highly correlated with the average 9-sample area-under-the-curve after the two single doses (r = 0.81, p = 0.0002). This correlation remained the same if the number of samples was reduced to 4, taken at time 1, 2.5, 4 and 24 hours. The C24 at steady-state was highly correlated with the 24-hour steady-state area-under-the-curve (r = 0.92, p < 0.0001). The average of the C24 values following the two single doses was also quite highly correlated with the steady-state area-under-the-curve (r = 0.72, p = 0

Estimating systemic exposure to ethinyl estradiol from an oral contraceptive.

PubMed

Westhoff, Carolyn L; Pike, Malcolm C; Tang, Rosalind; DiNapoli, Marianne N; Sull, Monica; Cremers, Serge

2015-05-01

This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive with steady-state values and to assess whether any simpler measures could provide an adequate proxy of the "gold standard" 24-hour steady-state area under the curve (AUC) value. Identification of a simple, less expensive measure of systemic ethinyl estradiol exposure would be useful for larger studies that are designed to assess the relationship between an individual's ethinyl estradiol exposure and side-effects. We collected 13 samples over 24 hours for pharmacokinetic analysis on days 1 and 21 of the first cycle of a monophasic oral contraceptive that contained 30 μg ethinyl estradiol and 150 μg levonorgestrel in 17 nonobese healthy white women. We also conducted an abbreviated single-dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of a full 13-sample steady-state pharmacokinetic analysis with results that had been calculated with the use of fewer samples (9 or 5) and after the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. The AUC, maximum, and 24-hour values were similar after the 2 single oral contraceptive doses (AUC; r=0.92). The steady-state 13-sample 24-hour AUC value was correlated highly with the average 9-sample AUC value after the 2 single doses (r=0.81; P=.0002). This correlation remained the same if the number of single-dose samples was reduced to 4, taken at time 1, 2.5, 4, and 24 hours. The 24-hour value at steady-state was correlated highly with the 24-hour steady-state AUC value (r=0.92; P<.0001). The average of the 24-hour values after the 2 single doses was also correlated quite highly with the steady-state AUC value (r=0.72; P=.0026). Limited blood sampling, including results from 2 single doses, gave highly

17β-estradiol in runoff as affected by various poultry litter application strategies.

PubMed

Delaune, P B; Moore, P A

2013-02-01

Steroidal hormones, which are excreted by all mammalian species, have received increasing attention in recent years due to potential environmental implications. The objective of this study was to evaluate 17β-estradiol concentrations in runoff water from plots receiving poultry litter applications using various management strategies. Treatments included the effects of 1) aluminum sulfate (alum) application rates to poultry litter; 2) time until the first runoff event occurs after poultry litter application; 3) poultry litter application rate; 4) fertilizer type; and 5) litter from birds fed modified diets. Rainfall simulators were used to cause continuous runoff from fertilized plots. Runoff samples were collected and analyzed for 17β-estradiol concentrations. Results showed that increasing alum additions to poultry litter decreased 17β-estradiol concentrations in runoff water. A significant exponential decline in 17β-estradiol runoff was also observed with increasing time until the first runoff event after litter application. Concentrations of 17β-estradiol in runoff water increased with increasing litter application rate and remained above background concentrations after three runoff events at higher application rates. Management practices such as diet modification and selection of fertilizer type were also shown to affect 17β-estradiol concentrations in runoff water. Although results from these experiments typically represented a worst case scenario since runoff events generally occurred immediately after litter application, the contaminant loss from pastures fertilized with poultry litter can be expected to be much lower than continual estradiol loadings observed from waste water treatment plants. Management practices such as alum amendment and application timing can significantly reduce the risk of 17β-estradiol losses in the environment. Copyright © 2012 Elsevier B.V. All rights reserved.

Congener Patterns of Persistent Organic Pollutants Establish the Extent of Contaminant Biotransport by Pacific Salmon in the Great Lakes.

PubMed

Gerig, Brandon S; Chaloner, Dominic T; Janetski, David J; Rediske, Richard R; O'Keefe, James P; Moerke, Ashley H; Lamberti, Gary A

2016-01-19

In the Great Lakes, introduced Pacific salmon (Oncorhynchus spp.) can transport persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), to new environments during their spawning migrations. To explore the nature and extent of POP biotransport by salmon, we compared 58 PCB and 6 PBDE congeners found in spawning salmon directly to those in resident stream fish. We hypothesized that stream fish exposed to salmon spawners would have congener patterns similar to those of salmon, the presumed contaminant source. Using permutational multivariate analysis of variance (PERMANOVA) and nonmetric multidimensional scaling (NMDS), we found that POP congener patterns of Pacific salmon varied among regions in the Great Lakes basin (i.e., Lake Huron, Lake Michigan, or Lake Superior), tissue type (whole fish or eggs), and contaminant type (PCB or PBDE). For stream-resident fish, POP congener pattern was influenced by the presence of salmon, location (i.e., Great Lakes Basin), and species identity (i.e., brook trout [Salvelinus fontinalis] or mottled sculpin [Cottus bairdii]). Similarity in congener patterns indicated that salmon are a source of POPs to brook trout in stream reaches receiving salmon spawners from Lake Michigan and Lake Huron but not from Lake Superior. Congener patterns of mottled sculpin differed from those of brook trout and salmon, suggesting that brook trout and mottled sculpin either use salmon tissue to differing degrees, acquire POPs from different dietary sources, or bioaccumulate or metabolize POPs differently. Overall, our analyses identified the important role of salmon in contaminant biotransport but also demonstrated that the extent of salmon-mediated POP transfer and uptake in Great Lakes tributaries is location- and species-specific.

THE PATHOBIOLOGY OF 17B-ESTRADIOL IN SUMMER FLOUNDER, PARALICHTYS DENTATUS

EPA Science Inventory

Estradiol has been shown to cause increased vitellogenin (VtG) concentrations in male fish. The intent of this study was to evaluate the pathobiology associated with exposure to 17 -estradiol (E2) on liver, gonad, and kidney tissues of summer flounder, Paralichthys dentatus. Juve...

SW-846 Test Method 8276: Toxaphene and Toxaphene Congeners By Gas Chromatography/Negative Ion Chemical Ionization Mass Spectrometry (GC-NICI/MS)

EPA Pesticide Factsheets

determine the concentrations of various toxaphene congeners and technical toxaphene (with other toxaphene congeners and compounds from Method 8081) in extracts from solidliquid matrices, using fused-silica, open-tubular capillary columns with (NICI/MS).

Short-chain chlorinated paraffins (SCCPs) in surface soil from a background area in China: occurrence, distribution, and congener profiles.

PubMed

Wang, Xue-Tong; Zhang, Yuan; Miao, Yi; Ma, Ling-Ling; Li, Yuan-Cheng; Chang, Yue-Ya; Wu, Ming-Hong

2013-07-01

Short-chain chlorinated paraffins (SCCPs) are extremely complex technical mixtures of polychlorinated n-alkanes with carbon chain lengths from C10 to C13 and chlorine content between 49 and 70%. SCCPs are under consideration for inclusion in the Stockholm Convention on persistent organic pollutants. SCCPs have been used extensively in industrial production, but little is known about the pollution level in soil environment in China. In this study, levels and distribution of SCCPs in soil samples from Chongming Island were analyzed. Concentrations of total SCCPs in soil samples ranged from 0.42 to 420 ng g(-1), with a median of 9.6 ng g(-1). The ubiquitous occurrence of SCCPs in Chongming Island implied that long-range atmospheric transport and soil-air exchange may be the most important pathways for SCCP contamination in the background area. The localized SCCP contamination could be derived from an unidentified source. Hierarchical cluster analysis indicated that C13- and C11-congeners were predominant in most soils and C10- and C12-congeners dominated in the remaining soils. Cl7- and Cl8-congeners were on the average the most dominant chlorine congeners in nearly all soils. Principal component analysis suggested that the separation of even and odd carbon chain congeners occurred during long-range atmospheric transport and aging in soil in the study area.

High estradiol levels improve false memory rates and meta-memory in highly schizotypal women.

PubMed

Hodgetts, Sophie; Hausmann, Markus; Weis, Susanne

2015-10-30

Overconfidence in false memories is often found in patients with schizophrenia and healthy participants with high levels of schizotypy, indicating an impairment of meta-cognition within the memory domain. In general, cognitive control is suggested to be modulated by natural fluctuations in oestrogen. However, whether oestrogen exerts beneficial effects on meta-memory has not yet been investigated. The present study sought to provide evidence that high levels of schizotypy are associated with increased false memory rates and overconfidence in false memories, and that these processes may be modulated by natural differences in estradiol levels. Using the Deese-Roediger-McDermott paradigm, it was found that highly schizotypal participants with high estradiol produced significantly fewer false memories than those with low estradiol. No such difference was found within the low schizotypy participants. Highly schizotypal participants with high estradiol were also less confident in their false memories than those with low estradiol; low schizotypy participants with high estradiol were more confident. However, these differences only approached significance. These findings suggest that the beneficial effect of estradiol on memory and meta-memory observed in healthy participants is specific to highly schizotypal individuals and might be related to individual differences in baseline dopaminergic activity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effect of diet on oxidation of 17 beta-estradiol in vivo.

PubMed

Musey, P I; Collins, D C; Bradlow, H L; Gould, K G; Preedy, J R

1987-10-01

The effect of a high fat, low carbohydrate, low protein diet on the in vivo oxidation of 17 beta-estradiol was studied using radiometric methods. Five male chimpanzees were fed a normal (13%) fat diet or a high (65%) fat diet for 8 weeks. After a 4-week rest period, the animals were fed the alternative diet. The mean percent oxidation of 16 alpha-[3H]estradiol-17 beta 24 h after injection was 3.8 +/- 1.3% (+/- SD) on the normal diet vs. 18.4 +/- 4.7% on the high fat diet (P less than 0.01). In contrast, the mean percent oxidation of 2-[3H]estradiol 24 h after injection was 31.6 +/- 3.8% (+/- SD) on the normal diet vs. 20.0 +/- 3.5% on the high fat diet (P less than 0.05). These results suggest that the oxidation of 17 beta-estradiol to estriols relative to that to catechol estrogens is increased by a high fat diet.

Concentration of polychlorinated biphenyl (PCB) congeners in the muscle of Clarias gariepinus and sediment from inland rivers of southwestern Nigeria and estimated potential human health consequences.

PubMed

Adeogun, Aina O; Chukwuka, Azubuike V; Okoli, Chukwunonso P; Arukwe, Augustine

2016-01-01

The distributions of polychlorinated biphenyl (PCB) congeners were determined in sediment and muscle of the African sharptooth catfish (Clarias gariepinus) from the Ogun and Ona rivers, southwest Nigeria. In addition, the effect of PCB congeners on condition factor (CF) and associated human health risk was assessed using muscle levels for a noncarcinogenic hazard quotient (HQ) calculation. Elevated concentrations of high-molecular-weight (HMW) PCB congeners were detected in sediment and fish downstream of discharge points of both rivers. A significant reduction in fish body weight and CF was observed to correlate with high PCB congener concentrations in the Ona River. A principal component (PC) biplot revealed significant site-related PCB congener distribution patterns for HMW PCB in samples from the Ogun River (71.3%), while the Ona River (42.6%) showed significant PCB congener patterns for low-molecular-weight (LMW) congeners. Biota-sediment accumulation factor (BSAF) was higher downstream for both rivers, presenting PCB congener-specific accumulation patterns in the Ona River. Significant decreases in fish body weight, length and CF were observed downstream compared to upstream in the Ona River. The non-carcinogenic HQ of dioxin-like congener 189 downstream in both rivers exceeded the HQ = 1 threshold for children and adults for both the Ogun and Ona rivers. Overall, our results suggest that industrial discharges contribute significantly to PCB inputs into these rivers, with potential for significant health implications for neighboring communities that utilize these rivers for fishing and other domestic purposes.

De Novo Synthesized Estradiol Protects against Methylmercury-Induced Neurotoxicity in Cultured Rat Hippocampal Slices

PubMed Central

Ishihara, Yasuhiro; Komatsu, Shota; Munetsuna, Eiji; Onizaki, Masahiro; Ishida, Atsuhiko; Kawato, Suguru; Mukuda, Takao

2013-01-01

Background Estrogen, a class of female sex steroids, is neuroprotective. Estrogen is synthesized in specific areas of the brain. There is a possibility that the de novo synthesized estrogen exerts protective effect in brain, although direct evidence for the neuroprotective function of brain-synthesized estrogen has not been clearly demonstrated. Methylmercury (MeHg) is a neurotoxin that induces neuronal degeneration in the central nervous system. The neurotoxicity of MeHg is region-specific, and the molecular mechanisms for the selective neurotoxicity are not well defined. In this study, the protective effect of de novo synthesized 17β-estradiol on MeHg-induced neurotoxicity in rat hippocampus was examined. Methodology/Principal Findings Neurotoxic effect of MeHg on hippocampal organotypic slice culture was quantified by propidium iodide fluorescence imaging. Twenty-four-hour treatment of the slices with MeHg caused cell death in a dose-dependent manner. The toxicity of MeHg was attenuated by pre-treatment with exogenously added estradiol. The slices de novo synthesized estradiol. The estradiol synthesis was not affected by treatment with 1 µM MeHg. The toxicity of MeHg was enhanced by inhibition of de novo estradiol synthesis, and the enhancement of toxicity was recovered by the addition of exogenous estradiol. The neuroprotective effect of estradiol was inhibited by an estrogen receptor (ER) antagonist, and mimicked by pre-treatment of the slices with agonists for ERα and ERβ, indicating the neuroprotective effect was mediated by ERs. Conclusions/Significance Hippocampus de novo synthesized estradiol protected hippocampal cells from MeHg-induced neurotoxicity via ERα- and ERβ-mediated pathways. The self-protective function of de novo synthesized estradiol might be one of the possible mechanisms for the selective sensitivity of the brain to MeHg toxicity. PMID:23405170

The daidzein- and estradiol- induced anorectic action in CCK or leptin receptor deficiency rats.

PubMed

Fujitani, Mina; Mizushige, Takafumi; Bhattarai, Keshab; Iwahara, Asami; Aida, Ryojiro; Kishida, Taro

2015-01-01

We investigated the effect of daidzein feeding and estradiol treatment on food intake in cholecystokinin-1 receptor (CCK1R) deficiency, leptin receptor (ObRb) deficiency rats and their wild-type rats. These rats underwent an ovariectomy or a sham operation. For the 5 week experiment, each rat was divided in three groups: control, daidzein (150 mg/kg diet), and estradiol (4.2 μg/rat/day) groups. In both CCK1R+ and CCK1R- rats, daidzein feeding and estradiol treatment significantly decreased food intake. Daidzein feeding significantly reduced food intake in ovariectomized ObRb- rats, although not in ObRb+ rats. Estradiol treatment significantly lowered food intake in ovariectomized ObRb+ and ObRb- rats. In the ovariectomized rats, estradiol treatment significantly increases uterine weight, while daidzein feeding did not change it, suggesting that daidzein might have no or weak estrogenic effect in our experiment. These results suggest that CCK1R and ObRb signalings were not essential for the daidzein- and estradiol-induced anorectic action.

Estradiol inhibits hepatic stellate cell area and collagen synthesis in the chicken liver.

PubMed

Nishimura, Shotaro; Teshima, Akifumi; Kawabata, Fuminori; Tabata, Shoji

2017-11-01

Hepatic stellate cells (HSCs) are the main collagen-producing cells in the liver. The HSC area and amount of collagen fibers are different between male and female chickens. This study was performed to confirm the effect of estradiol on collagen synthesis in the growing chicken liver. Blood estradiol levels in chicks were compared at 4 and 8 weeks of age, and the collagen fibril network in liver tissue was observed at 8 weeks by scanning electron microscopy. Intraperitoneal administrations of estradiol and tamoxifen to male and female chicks, respectively, were performed daily from 5 to 8 weeks of age. The areas of HSCs and collagen contents were measured in the liver tissue. The blood estradiol level was higher in females than in males, and the collagen fibril network was denser in males than in females at 8 weeks of age. Estradiol administration in males induced decreases in the HSC area and collagen content of the liver. Conversely, tamoxifen administration in females induced an increase in the HSC area but did not facilitate collagen synthesis. Based on these results, estradiol inhibits the area and collagen synthesis of HSCs in the growing chicken liver under normal physiological conditions. © 2017 Japanese Society of Animal Science.

A Mouse Model of Hypospadias Induced by Estradiol Benzoate.

PubMed

He, Hou-Guang; Han, Cong-Hui; Zhang, Wei

2015-12-01

We wished to establish a mouse model of hypospadias using injections of estradiol benzoate for investigating the molecular mechanisms of hypospadias. Fifty timed pregnant mice were randomly divided into five study groups: A, B, C, D, and E. These groups were injected subcutaneously with estradiol benzoate mixed with sesame oil at, respectively, the doses of 0, 0.1, 0.5, 2.5, or 12.5 mg kg(-1) days(-1) from gestation day (GD) 12 to GD 16. The pups' mortality was recorded on the day of delivery. Urethras and positions of testes were examined on postnatal day 28. The numbers of live pups were significantly lower in the study groups D and E compared to study group A (p < 0.01). Hypospadias was seen in groups C (3.3 %; 1/30), D (18.2 %; 4/22), and E (21.4 %; 3/14), while cryptorchidism was observed in groups C (10 %; 3/30), D (31.8 %; 7/22), and E (57.1 %; 8/14) on postnatal day 28. The experimental model of hypospadias induced by estradiol benzoate in the group D (2.5 mg kg(-1) days(-1)) was more reliable considering high mortality of the study group E. The dose of estradiol benzoate used in the group D is suitable for establishing mouse model of hypospadias.

MODELLING OF POLYCHLORINATED-DIOXIN AND -FURAN CONGENER PROFILES FROM MUNICIPAL WASTE COMBUSTION

EPA Science Inventory

The paper discusses a model, based on experimental data, that was developed to describe the profile of polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) congeners formed in the duct region of a pilot-scale combustor simulating large-scale municipal w...

Comparative Biological Effects and Potency of 17a- and 17ß-Estradiol In Fathead Minnows

USDA-ARS?s Scientific Manuscript database

17ß-estradiol is the most potent natural estrogen commonly found in anthropogenically altered environments and has been the focus of many toxicological laboratory studies. However, fewer aquatic toxicological data on the effects of 17a-estradiol, a diastereoisomer of 17ß-estradiol, exists in the li...

Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol.

PubMed

Hodis, Howard N; Mack, Wendy J; Henderson, Victor W; Shoupe, Donna; Budoff, Matthew J; Hwang-Levine, Juliana; Li, Yanjie; Feng, Mei; Dustin, Laurie; Kono, Naoko; Stanczyk, Frank Z; Selzer, Robert H; Azen, Stanley P

2016-03-31

Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested. A total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima-media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen. After a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P=0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum. Oral estradiol

Estradiol enhances the acquisition of lithium chloride-induced conditioned taste aversion in castrated male rats

NASA Astrophysics Data System (ADS)

Lin, Shih-Fan; Tsai, Yuan-Feen; Tai, Mei-Yun; Yeh, Kuei-Ying

2015-10-01

The present study examined the effects of short-term treatment with ovarian hormones on the acquisition of conditioned taste aversion (CTA). Adult male rats were castrated and randomly divided into LiCl- and saline-treated groups. Nineteen days after castration, all of the animals were subjected to 23.5-h daily water deprivation for seven successive days (day 1 to day 7). On the conditioning day (day 8), the rats received either a 4 ml/kg of 0.15 M LiCl or the same dose of saline injection immediately after administration of a 2 % sucrose solution during the 30-min water session. Starting from day 6, rats in both groups received one of the following treatments: daily subcutaneous injection of (1) estradiol alone (30 μg/kg; estradiol benzoate (E) group), (2) estradiol plus progesterone (500 μg; E + progesterone (P) group), or (3) olive oil. From day 9 to day 11, all of the rats were given daily two-bottle preference tests during the 30-min fluid session. The estradiol and estradiol plus progesterone treatments in the LiCl groups resulted in significantly lower preference scores for the sucrose solution compared with the olive oil treatment groups, but no difference in preference score was seen between these two groups. These results indicate that both the estradiol and estradiol plus progesterone treatments in the LiCl groups enhanced the acquisition of CTA learning and suggest that estradiol affects the acquisition of CTA mediated by an activational effect in male rats, whereas progesterone treatment does not influence the effects of estradiol on the acquisition of CTA.

Regulation of preovulatory estradiol and its impacts throughout the bovine estrous cycle

USDA-ARS?s Scientific Manuscript database

Preovulatory estradiol has been reported to play a critical role in follicular cell growth, initiation of estrus, oocyte maturation, sperm transport, uterine environment, and embryo survival. Furthermore, cattle with elevated preovulatory estradiol (HighE2) concentrations prior to fixed time AI had...

An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate/dienogest

PubMed Central

Fruzzetti, Franca; Trémollieres, Florence; Bitzer, Johannes

2012-01-01

Natural estrogens such as estradiol (E2) or its valerate ester (E2V) offer an alternative to ethinyl estradiol (EE). E2-containing combined oral contraceptives (COCs) have demonstrated sufficient ovulation inhibition and acceptable contraceptive efficacy. However, earlier formulations were generally associated with unacceptable bleeding profiles. Two E2V-containing preparations have been approved to date for contraceptive use: E2V/cypro-terone acetate (CPA) (Femilar®; only approved in Finland and only in women >40 years or women aged 35–40 years in whom a COC containing EE is not appropriate) and E2V/dienogest (DNG; Qlaira®/Natazia®). The objective of the current review is to provide an overview of the development of COCs containing natural estrogen, highlighting past issues and challenges faced by earlier formulations, as well as the current status and future directions. The majority of information to date pertains to the development of E2V/DNG. PMID:22468839

Mesencephalic neuron death induced by congeners of nitrogen monoxide is prevented by the lazaroid U-83836E.

PubMed

Grasbon-Frodl, E M; Brundin, P

1997-01-01

We explored the effects of congeners of nitrogen monoxide (NO) on cultured mesencephalic neurons. Sodium nitroprusside (SNP) was used as a donor of NO, the congeners of which have been found to exert either neurotoxic or neuroprotective effects depending on the surrounding redox milieu. In contrast to a previous report that suggests that the nitrosonium ion (NO+) is neuroprotective to cultured cortical neurons, we found that the nitrosonium ion reduces the survival of cultured dopamine neurons to 32% of control. There was a trend for further impairment of dopamine neuron survival, to only 7% of untreated control, when the cultures were treated with SNP plus ascorbate, i.e. when the nitric oxide radical (NO.) had presumably been formed. We also evaluated the effects of an inhibitor of lipid peroxidation, the lazaroid U-83836E, against SNP toxicity. U-83836E exerted marked neuroprotective effects in both insult models. More than twice as many dopamine neurons (75% of control) survived when the lazaroid was added to SNP-treated cultures and the survival was increased eight-fold (to 55% of control) when U-83836E was added to cultures treated with SNP plus ascorbate. We conclude that the congeners of NO released by SNP are toxic to mesencephalic neurons in vitro and that the lazaroid U-83836E significantly increases the survival of dopamine neurons in situations where congeners of NO are generated.

Towards a global historical emission inventory for selected PCB congeners--a mass balance approach 3. An update.

PubMed

Breivik, Knut; Sweetman, Andy; Pacyna, Jozef M; Jones, Kevin C

2007-05-15

Previously published estimates of the global production, consumption and atmospheric emissions of 22 individual PCB congeners [Breivik K, Sweetman A, Pacyna JM, Jones KC. Towards a global historical emission inventory for selected PCB congeners - a mass balance approach. 1. Global production and consumption. Sci Total Environ 2002a; 290: 181-198.; Breivik K, Sweetman A, Pacyna JM, Jones KC. Towards a global historical emission inventory for selected PCB congeners--a mass balance approach. 2. Emissions. Sci Total Environ 2002b; 290: 181-198.] have provided useful information for later studies attempting to interpret contaminant levels in remote areas as well as in the global environment. As a result of the need for more contemporary emission data (following the year 2000), an update of this emission database is presented. This exercise takes into account new information on PCB production in Poland, as well as new data on the chemical composition of various technical mixtures for which less information had been available. The methodology to estimate temporal trends of PCB emissions associated with various types of PCB usage is improved. Projected emissions up to year 2100 are presented to facilitate predictions of future environmental exposure. The national emission data for each of the 114 countries considered is spatially resolved on a 1 degrees x1 degrees grid for each congener and year, using population density as a surrogate.

17β-Estradiol administration promotes delayed cutaneous wound healing in 40-week ovariectomised female mice.

PubMed

Mukai, Kanae; Nakajima, Yukari; Urai, Tamae; Komatsu, Emi; Nasruddin; Sugama, Junko; Nakatani, Toshio

2016-10-01

This study investigated the effect of 17β-estradiol on wound healing in 40-week ovariectomised female mice. Thirty-six-week-old female mice were divided into three groups: medication with 17β-estradiol after ovariectomy (OVX + 17β-estradiol), ovariectomy (OVX) and sham (SHAM). The mice received two full-thickness wounds, and the OVX + 17β-estradiol group was administered 17β-estradiol at 0·01 g/day until healing. In the OVX + 17β-estradiol group, the ratio of wound area was significantly smaller than those of the OVX and SHAM groups on days 1-3, 5, 6, 8-12 and 9-12, respectively, the numbers of neutrophils and macrophages were significantly smaller than those on days 3 and 7, the ratio of re-epithelialisation was significantly higher than those on days 3 and 11, the ratio of myofibroblasts was significantly higher than those on day 11 and smaller on day 14, and the ratio of collagen fibres was significantly larger than that of the OVX group on days 7-14. We found that 17β-estradiol administration promotes cutaneous wound healing in 40-week female mice by reducing wound area, shortening inflammatory response, and promoting re-epithelialisation, collagen deposition and wound contraction. Our results suggest that cutaneous wound healing that is delayed because of ageing is promoted by exogenous and continuous 17β-estradiol administration. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Profiles of polychlorinated biphenyl congeners, organochlorine pesticides and butlyns in southern sea otters and their prey

USGS Publications Warehouse

Kannan, K.; Kajiwara, N.; Watanabe, M. E.; Nakata, H.; Thomas, N.J.; Stephenson, M.; Jessup, David A.; Tanabe, S.

2004-01-01

Concentrations of organochlorine pesticides, polychlorinated biphenyl (PCB) congeners, and butyltins were measured in sea otters and selected prey species (invertebrates) collected from the California (USA) coast. Polychlorinated biphenyls, DDTs (sum of p,pa??-dichlorodiphenyldichloroethylene [p,pa??-DDE], p,pa??-dichlorodiphenyldichloroethane [p,pa??-DDD], and p,pa??-DDT), and butyltins were the major contaminants found in sea otters and their prey. Lipid-normalized concentrations of PCBs and DDT in sea otter livers were 60- and 240-fold greater than those found in the prey. Great biomagnification of PCBs and DDT in sea otters is suggested to result from their high per-capita intake of diet compared with those of other marine mammals. Profiles of PCB congeners in sea otters and prey species suggest a great capacity of sea otters to biotransform lower-chlorinated congeners. Sea otters seem to possess a greater ability than cetaceans to metabolize PCBs. The 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents of non- and mono-ortho PCBs in sea otters and certain prey species were at or above the theoretical threshold for toxic effects.

Estradiol causes the rapid accumulation of cAMP in human prostate.

PubMed Central

Nakhla, A M; Khan, M S; Romas, N P; Rosner, W

1994-01-01

Androgens are widely acknowledged to be central to the pathogenesis of benign prostatic hypertrophy (BPH). However, BPH increases in prevalence as men age, at precisely the stage of life when plasma androgens are decreasing. The decrease in total plasma androgens is amplified by an age-related increase in plasma sex hormone-binding globulin (SHBG) that results in a relatively greater decrease in free androgens than in total androgens. In addition, estrogens have long been suspected to be important in BPH, but a direct effect on the human prostate has never been demonstrated. We present data that are consistent with a role for estradiol, and for a decrease in androgens and an increase in SHBG, in the pathogenesis of BPH. We show that estradiol, but not dihydrotestosterone, acts in concert with SHBG to produce an 8-fold increase in intracellular cAMP in human BPH tissue. This increase is not blocked by an antiestrogen and is not provoked by an estrogen (diethylstilbestrol) that does not bind to SHBG, thus excluding the classic estrogen receptor as being operative in these events. Conversely, dihydrotestosterone, which blocks the binding of estradiol to SHBG, completely negates the effect of estradiol. Finally, we demonstrate that the SHBG-steroid-responsive second-messenger system is primarily localized to the prostatic stromal cells and not to the prostatic epithelial cells. Thus, we have shown a cell-specific, powerful, nontranscriptional effect of estradiol on the human prostate. PMID:7515502

PCB congener analysis with Hall electrolytic conductivity detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edstrom, R.D.

1989-01-01

This work reports the development of an analytical methodology for the analysis of PCB congeners based on integrating relative retention data provided by other researchers. The retention data were transposed into a multiple retention marker system which provided good precision in the calculation of relative retention indices for PCB congener analysis. Analytical run times for the developed methodology were approximately one hour using a commercially available GC capillary column. A Tracor Model 700A Hall Electrolytic Conductivity Detector (HECD) was employed in the GC detection of Aroclor standards and environmental samples. Responses by the HECD provided good sensitivity and were reasonablymore » predictable. Ten response factors were calculated based on the molar chlorine content of each homolog group. Homolog distributions were determined for Aroclors 1016, 1221, 1232, 1242, 1248, 1254, 1260, 1262 along with binary and ternary mixtures of the same. These distributions were compared with distributions reported by other researchers using electron capture detection as well as chemical ionization mass spectrometric methodologies. Homolog distributions acquired by the HECD methodology showed good correlation with the previously mentioned methodologies. The developed analytical methodology was used in the analysis of bluefish (Pomatomas saltatrix) and weakfish (Cynoscion regalis) collected from the York River, lower James River and lower Chesapeake Bay in Virginia. Total PCB concentrations were calculated and homolog distributions were constructed from the acquired data. Increases in total PCB concentrations were found in the analyzed fish samples during the fall of 1985 collected from the lower James River and lower Chesapeake Bay.« less

Altered functional brain asymmetry for mental rotation: effect of estradiol changes across the menstrual cycle.

PubMed

Zhu, Xun; Kelly, Thomas H; Curry, Thomas E; Lal, Chitra; Joseph, Jane E

2015-09-30

Mental rotation is a visuospatial task associated with pronounced sex differences. Performance is also affected by gonadal hormones such as testosterone and estradiol. To better understand hormonal modulation of the neural substrates of mental rotation, the present study examined the influence of estradiol using functional MRI. Ten premenopausal women were tested on a 3D mental rotation task during the early follicular and late follicular phases of the menstrual cycle. Change in estradiol between the two phases was confirmed by hormone assays. Brain activation patterns were similar across the two phases, but the change in estradiol had different associations with the two hemispheres. Better performance in the late follicular than the early follicular phase was associated with a pattern of reduced recruitment of the right hemisphere and increased recruitment of the left hemisphere. The increased recruitment of the left hemisphere was directly associated with greater changes in estradiol. Given that the right hemisphere is the dominant hemisphere in visuospatial processing, our results suggest that estradiol is associated with reduced functional asymmetry, consistent with recent accounts of hormonal modulation of neurocognitive function.

Peri-pubertal high caffeine exposure increases ovarian estradiol production in immature rats.

PubMed

Kwak, Yoojin; Choi, Hyeonhae; Bae, Jaeman; Choi, Yun-Young; Roh, Jaesook

2017-04-01

Chronic caffeine consumption exerts a negligible effect on the reproductive organs of normal adult females, but it is not known whether this is also true for children and adolescents. Here, we investigated the effects of high caffeine exposure on sexual maturation and ovarian estradiol production in immature female rats. Immature female SD rats were divided into controls and caffeine groups fed 120 and 180mg/kg/day for 4 or 8 weeks. There was a significant delay in vaginal opening in the caffeine-fed groups. In addition, serum estradiol levels were elevated in the caffeine-fed animals after 2 and 4 weeks of exposure. Estradiol secretion as well as aromatase expression also increased significantly in the ovarian cells in response to caffeine. These results demonstrate that peripubertal exposure to high caffeine increases estradiol production in the ovary; this may disturb the coordinated regulation of the hypothalamo-pituitary-ovarian axis, thereby interfering with sexual maturation. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanism of the Rapid Effect of 17β -Estradiol on Medial Amygdala Neurons

NASA Astrophysics Data System (ADS)

Nabekura, Junichi; Oomura, Yutaka; Minami, Taketsugu; Mizuno, Yuji; Fukuda, Atsuo

1986-07-01

The mechanism by which sex steroids rapidly modulate the excitability of neurons was investigated by intracellular recording of neurons in rat medial amygdala brain slices. Brief hyperpolarization and increased potassium conductance were produced by 17β - estradiol. This effect persisted after elimination of synaptic input and after suppression of protein synthesis. Thus, 17β -estradiol directly changes the ionic conductance of the postsynaptic membrane of medial amygdala neurons. In addition, a greater proportion of the neurons from females than from males responded to 17β -estradiol.

Levels of toxaphene congeners in white whales (Delphinapterus leucas) from Svalbard, Norway.

PubMed

Andersen, G; Føreid, S; Skaare, J U; Jenssen, B M; Lydersen, C; Kovacs, K M

2006-03-15

This study reports concentrations of three pesticide toxaphene congeners (CHBs; CHB-26, -50 and -62) from the blubber of ten adult, male white whales (Delphinapterus leucas) from Svalbard, Norway. The CHB congeners that occurred at the highest levels in the blubber of the white whales were, as expected, CHB-26 (4636+/-1992 (SD) ng/g l.w.) and CHB-50 (6579+/-2214 ng/g l.w.); CHB-62 (232+/-231 ng/g l.w.) was also present, but at much lower concentrations. The mean level of the sum of the three CHBs (SigmaCHBs = 11,447+/-4208 ng/g l.w.) in this study is more than twice the mean concentrations of the well-known organochlorine (OC) pollutants SigmaDDTs (sum of pp'-DDT, pp'-DDE, pp'-DDD) and SigmaPCBs (sum of 27 PCB congeners) previously reported from the same individual white whales. The concentrations of CHBs in white whales from Svalbard are at the high end of the range for concentrations of these compounds compared to other Arctic white whale populations. Additionally, the contribution of CHBs to the overall OC burden is larger in white whales from Svalbard compared with their counterparts from other areas in the Arctic. Male white whales from Svalbard have several orders of magnitude higher concentrations of SigmaCHBs compared to seals and polar bears (Ursus maritimus) from the same area. The high levels of CHBs in these whales, and their dominance in the OC pattern, suggests that white whales in Svalbard are exposed to high levels of this group of contaminants. Further studies are needed to investigate possible effects of CHBs and other OC contaminants on the white whale population in Svalbard.

Estradiol therapy in adulthood reverses glial and neuronal alterations caused by perinatal asphyxia.

PubMed

Saraceno, Gustavo Ezequiel; Bertolino, María Laura Aón; Galeano, Pablo; Romero, Juan Ignacio; Garcia-Segura, Luis Miguel; Capani, Francisco

2010-06-01

The capacity of the ovarian hormone 17beta-estradiol to prevent neurodegeneration has been characterized in several animal models of brain and spinal cord pathology. However, the potential reparative activity of the hormone under chronic neurodegenerative conditions has received less attention. In this study we have assessed the effect of estradiol therapy in adulthood on chronic glial and neuronal alterations caused by perinatal asphyxia (PA) in rats. Four-month-old male Sprague-Dawley rats submitted to PA just after delivery, and their control littermates, were injected for 3 consecutive days with 17beta estradiol or vehicle. Animals subjected to PA and treated with vehicle showed an increased astrogliosis, focal swelling and fragmented appearance of MAP-2 immunoreactive dendrites, decreased MAP-2 immunoreactivity and decreased phosphorylation of high and medium molecular weight neurofilaments in the hippocampus, compared to control animals. Estradiol therapy reversed these alterations. These findings indicate that estradiol is able to reduce, in adult animals, chronic reactive astrogliosis and neuronal alterations caused by an early developmental neurodegenerative event, suggesting that the hormone might induce reparative actions in the Central Nervous System (CNS). Copyright (c) 2009 Elsevier Inc. All rights reserved.

Coplanar polychlorinated biphenyl congeners in shark livers from the north-western African Atlantic ocean

DOE Office of Scientific and Technical Information (OSTI.GOV)

Serrano, R.; Fernandez, M.A.; Hernandez, L.M.

1997-01-01

Polychlorinated biphenyls have been widely used by industry throughout the world since 1930. Although their use has been banned in many countries since the late 1970s, they still represent an important class of priority pollutants due to their persistence. Most open uses of these chemicals have been severely curtailed in industrialized nations, but a considerable fraction of past productions is probably still cycling in the ecosphere. In recent years, attention has been focused on the toxicity of PCBs, especially of those congeners showing similar toxicity as the polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDFs). It has been shown that PCB congeners`more » toxicity largely depends on the chlorine substitution pattern. The most toxic PCB cogeners are those with two para chlorines, at least two meta chlorines and 0-2 ortho chlorines. These so-called {open_quotes}coplanar{close_quotes} (non- mono- and di-ortho) PCB cogeners are able to obtain planar conformation. Recently, toxic equivalence factors have been assigned to coplanar PCBs. Thus determination of individual PCB cogeners is important for evaluating the toxic potentials of PCB residues in, for example, wildlife. This paper presents preliminary results of a study looking at levels of PCB congeners, including coplanar ones, in the liver of six shark species, collected in the North African Atlantic Ocean. 15 refs., 2 figs., 2 tabs.« less

Selectivity of coronaridine congeners at nicotinic acetylcholine receptors and inhibitory activity on mouse medial habenula.

PubMed

Arias, Hugo R; Jin, Xiaotao; Feuerbach, Dominik; Drenan, Ryan M

2017-11-01

The inhibitory activity of coronaridine congeners on human (h) α4β2 and α7 nicotinic acetylcholine receptors (AChRs) is determined by Ca 2+ influx assays, whereas their effects on neurons in the ventral inferior (VI) aspect of the mouse medial habenula (MHb) are determined by patch-clamp recordings. The Ca 2+ influx results clearly establish that coronaridine congeners inhibit hα3β4 AChRs with higher selectivity compared to hα4β2 and hα7 subtypes, and with the following potency sequence, for hα4β2: (±)-18-methoxycoronaridine [(±)-18-MC]>(+)-catharanthine>(±)-18-methylaminocoronaridine [(±)-18-MAC] ∼ (±)-18-hydroxycoronaridine [(±)-18-HC]; and for hα7: (+)-catharanthine>(±)-18-MC>(±)-18-HC>(±)-18-MAC. Interestingly, the inhibitory potency of (+)-catharanthine (27±4μM) and (±)-18-MC (28±6μM) on MHb (VI) neurons was lower than that observed on hα3β4 AChRs, suggesting that these compounds inhibit a variety of endogenous α3β4* AChRs. In addition, the interaction of bupropion with (-)-ibogaine sites on hα3β4 AChRs is tested by [ 3 H]ibogaine competition binding experiments. The results indicate that bupropion binds to ibogaine sites at desensitized hα3β4 AChRs with 2-fold higher affinity than at resting receptors, suggesting that these compounds share the same binding sites. In conclusion, coronaridine congeners inhibit hα3β4 AChRs with higher selectivity compared to other AChRs, by interacting with the bupropion (luminal) site. Coronaridine congeners also inhibit α3β4*AChRs expressed in MHb (VI) neurons, supporting the notion that these receptors are important endogenous targets for their anti-addictive activities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selectivity of coronaridine congeners at nicotinic acetylcholine receptors and inhibitory activity on mouse medial habenula

PubMed Central

Arias, Hugo R.; Jin, Xiaotao; Feuerbach, Dominik; Drenan, Ryan M.

2018-01-01

The inhibitory activity of coronaridine congeners on human (h) α4β2 and α7 nicotinic acetylcholine receptors (AChRs) is determined by Ca2+ influx assays, whereas their effects on neurons in the ventral inferior (VI) aspect of the mouse medial habenula (MHb) are determined by patch-clamp recordings. The Ca2+ influx results clearly establish that coronaridine congeners inhibit hα3β4 AChRs with higher selectivity compared to hα4β2 and hα7 subtypes, and with the following potency sequence, for hα4β2: (±)-18-methoxycoronaridine [(±)-18-MC] > (+)-catharanthine > (±)-18-methylaminocoronaridine [(±)-18-MAC] ∼ (±)-18-hydroxycoronaridine [(±)-18-HC]; and for hα7: (+)-catharanthine > (±)-18-MC > (±)-18-HC > (±)-18-MAC. Interestingly, the inhibitory potency of (+)-catharanthine (27 ± 4 μM) and (±)-18-MC (28 ± 6 μM) on MHb (VI) neurons was lower than that observed on hα3β4 AChRs, suggesting that these compounds inhibit a variety of endogenous α3β4* AChRs. In addition, the interaction of bupropion with (−)-ibogaine sites on hα3β4 AChRs is tested by [3H]ibogaine competition binding experiments. The results indicate that bupropion binds to ibogaine sites at desensitized hα3β4 AChRs with 2-fold higher affinity than at resting receptors, suggesting that these compounds share the same binding sites. In conclusion, coronaridine congeners inhibit hα3β4 AChRs with higher selectivity compared to other AChRs, by interacting with the bupropion (luminal) site. Coronaridine congeners also inhibit α3β4*AChRs expressed in MHb (VI) neurons, supporting the notion that these receptors are important endogenous targets for their anti-addictive activities. PMID:29042244

Preparation and characterization of marine sponge collagen nanoparticles and employment for the transdermal delivery of 17beta-estradiol-hemihydrate.

PubMed

Nicklas, Martina; Schatton, Wolfgang; Heinemann, Sascha; Hanke, Thomas; Kreuter, Jörg

2009-09-01

Transdermal administration of estradiol offers advantages over oral estrogens for hormone replacement therapy regarding side effects by bypassing the hepatic presystemic metabolism. The objective of this study was to develop nanoparticles of Chondrosia reniformis sponge collagen as penetration enhancers for the transdermal drug delivery of 17beta-estradiol-hemihydrate in hormone replacement therapy. Collagen nanoparticles were prepared by controlled alkaline hydrolysis and characterized using atomic force microscopy and photon correlation spectroscopy. Estradiol-hemihydrate was loaded to the nanoparticles by adsorption to their surface, whereupon a drug loading up to 13.1% of sponge collagen particle mass was found. After incorporation of drug-loaded nanoparticles in a hydrogel, the estradiol transdermal delivery from the gel was compared with that from a commercial gel that did not contain nanoparticles. Saliva samples in postmenopausal patients showed significantly higher estradiol levels after application of the gel with nanoparticles. The area under the curve (AUC) for estradiol time-concentration curves over 24 hours was 2.3- to 3.4-fold higher and estradiol levels 24 hours after administration of estradiol were at least twofold higher with the nanoparticle gel. The hydrogel with estradiol-loaded collagen nanoparticles enabled a prolonged estradiol release compared to a commercial gel and yielded a considerably enhanced estradiol absorption. Consequently, sponge collagen nanoparticles represent promising carriers for transdermal drug delivery.

Addition of Estradiol to Cross-Sex Testosterone Therapy Reduces Atherosclerosis Plaque Formation in Female ApoE-/- Mice.

PubMed

Goetz, Laura G; Mamillapalli, Ramanaiah; Sahin, Cagdas; Majidi-Zolbin, Masoumeh; Ge, Guanghao; Mani, Arya; Taylor, Hugh S

2018-02-01

The contributions of estradiol and testosterone to atherosclerotic lesion progression are not entirely understood. Cross-sex hormone therapy (XHT) for transgender individuals dramatically alters estrogen and testosterone levels and consequently could have widespread consequences for cardiovascular health. Yet, no preclinical research has assessed atherosclerosis risk after XHT. We examined the effects of testosterone XHT after ovariectomy on atherosclerosis plaque formation in female mice and evaluated whether adding low-dose estradiol to cross-sex testosterone treatments after ovariectomy reduced lesion formation. Six-week-old female ApoE-/- C57BL/6 mice underwent ovariectomy and began treatments with testosterone, estradiol, testosterone with low-dose estradiol, or vehicle alone until euthanized at 23 weeks of age. Atherosclerosis lesion progression was measured by Oil Red O stain and confirmed histologically. We found reduced atherosclerosis in the estradiol- and combined testosterone/estradiol-treated mice compared with those treated with testosterone or vehicle only in the whole aorta (-75%), aortic arch (-80%), and thoracic aorta (-80%). Plaque size was similarly reduced in the aortic sinus. These reductions in lesion size after combined testosterone/estradiol treatment were comparable to those obtained with estrogen alone. Testosterone/estradiol combined therapy resulted in less atherosclerosis plaque formation than either vehicle or testosterone alone after ovariectomy. Testosterone/estradiol therapy was comparable to estradiol replacement alone, whereas mice treated with testosterone only fared no better than untreated controls after ovariectomy. Adding low-dose estrogen to cross-sex testosterone therapy after oophorectomy could improve cardiovascular outcomes for transgender patients. Additionally, these results contribute to understanding of the effects of estrogen and testosterone on atherosclerosis progression. Copyright © 2018 Endocrine Society.

Voluntary Exercise Impairs Initial Delayed Spatial Alternation Performance in Estradiol Treated Ovariectomized Middle-Aged Rats

PubMed Central

Neese, Steven L.; Korol, Donna L.; Schantz, Susan L.

2013-01-01

Estrogens differentially modulate behavior in the adult female rodent. Voluntary exercise can also impact behavior, often reversing age associated decrements in memory processes. Our research group has published a series of papers reporting a deficit in the acquisition of an operant working memory task, delayed spatial alternation (DSA), following 17β-estradiol treatment to middle-aged ovariectomized (OVX) rats. The current study examined if voluntary exercise could attenuate the 17β-estradiol induced deficits on DSA performance. OVX 12-month old Long- Evans rats were implanted with a Silastic capsule containing 17β-estradiol (10% in cholesterol: low physiological range) or with a blank capsule. A subset of the 17β-estradiol and OVX untreated rats were given free access to a running wheel in their home cage. All rats were tested for 40 sessions on the DSA task. Surprisingly, we found running wheel access to impair initial acquisition of the DSA task in 17β-estradiol treated rats, an effect not seen in OVX untreated rats given running wheel access. This deficit was driven by an increase in perseverative responding on a lever no longer associated with reinforcement. We also report for the first time a 17β-estradiol induced impairment on the DSA task following a long intertrial delay (18-sec), an effect revealed following more extended testing than in our previous studies (15 additional sessions). Overall, running wheel access increased initial error rate on the DSA task in 17β-estradiol treated middle-aged OVX rats, and failed to prevent the 17β-estradiol induced deficits in performance of the operant DSA task in later testing sessions. PMID:24013039

GPER expressed on microglia mediates the anti-inflammatory effect of estradiol in ischemic stroke.

PubMed

Zhao, Tian-Zhi; Ding, Qian; Hu, Jun; He, Shi-Ming; Shi, Fei; Ma, Lian-Ting

2016-04-01

Stroke could lead to serious morbidity, of which ischemic stroke counts for majority of the cases. Inflammation plays an important role in the pathogenesis of ischemic stroke, thus drugs targeting inflammation could be potentially neuroprotective. Estradiol was shown to be neuroprotective as well as anti-inflammatory in animal models of ischemic stroke with unclear mechanism. We hypothesize that the anti-inflammatory and neuroprotective effect of estradiol is mediated by the estradiol receptor G protein-coupled estrogen receptor 1 (GPER) expressed on microglia. We have generated the rat global cerebral ischemic model and the primary microglia culture to study the neuroprotective and anti-inflammatory effect of estradiol. We have further used pharmacological methods and siRNA knockdown approach to study the underlying mechanism. We found that estradiol reduced the level of proinflammatory cytokines including IL-1β and TNF-α, both in vivo and in vitro. We also found that the specific GPER agonist G1 could reduce the level of IL-1β (P = 0 P = 0.0017, one-way ANOVA and post hoc test) and TNF-α (P < 0.0001) in the primary microglia culture. Moreover, the specific GPER antagonist G15 was able to abolish the anti-inflammatory effect of estradiol. Estradiol failed to reduce the level of IL-1β (P = 0.4973, unpaired Student's t-test) and TNF-α (P = 0.1627) when GPER was knocked down. Our studies have suggested that GPER expressed on microglia mediated the anti-inflammatory effect of estradiol after ischemic stroke. Our studies could potentially help to develop more specific drugs to manage inflammation postischemic stroke.

Interactions between estradiol and haloperidol on perseveration and reversal learning in amphetamine-sensitized female rats.

PubMed

Almey, Anne; Arena, Lauren; Oliel, Joshua; Shams, Waqqas M; Hafez, Nada; Mancinelli, Cynthia; Henning, Lukas; Tsanev, Aleks; Brake, Wayne G

2017-03-01

There are sex differences associated with schizophrenia, as women exhibit later onset of the disorder, less severe symptomatology, and better response to antipsychotic medications. Estrogens are thought to play a role in these sex differences; estrogens facilitate the effects of antipsychotic medications to reduce the positive symptoms of schizophrenia, but it remains unclear whether estrogens protect against the cognitive symptoms of this disorder. Amphetamine sensitization is used to model some symptoms of schizophrenia in rats, including cognitive deficits like excessive perseveration and slower reversal learning. In this experiment female rats were administered a sensitizing regimen of amphetamine to mimic these cognitive symptoms. They were ovariectomized and administered either low or high estradiol replacement as well as chronic administration of the antipsychotic haloperidol, and were assessed in tests of perseveration and reversal learning. Results of these experiments demonstrated that, in amphetamine-sensitized rats, estradiol alone does not affect perseveration or reversal learning. However, low estradiol facilitates a 0.25mg/day dose of haloperidol to reduce perseveration and improve reversal learning. Combined high estradiol and 0.25mg/day haloperidol has no effect on perseveration or reversal learning, but high estradiol facilitates the effects of 0.13mg/day haloperidol to reduce perseveration and improve reversal learning. Thus, in amphetamine-sensitized female rats, 0.25mg/day haloperidol only improved perseveration and reversal learning when estradiol was low, while 0.13mg/day haloperidol only improved these cognitive processes when estradiol was high. These findings suggest that estradiol facilitates the effects of haloperidol to improve perseveration and reversal learning in a dose-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

A rapid enhancement of locomotor sensitization to amphetamine by estradiol in female rats.

PubMed

Zovkic, Iva B; McCormick, Cheryl M

2017-11-14

Estradiol moderates the effects of drugs of abuse in both humans and rodents. Estradiol's enhancement of behavioral effects resulting from high (>2.5mg/kg) doses of amphetamine is established in rats; there is less evidence for the role of estradiol in locomotor effects elicited by lower doses, which are less aversive, increase incentive motivation, involve different neural mechanisms than higher doses, and often more readily reveal group differences than do higher doses. Further, the extent to which estradiol is required for the induction versus the expression of sensitization is unknown. To establish a protocol, we replicated the effects of estradiol on locomotor sensitization to amphetamine reported in a previous study that involved a high locomotor-activating dose (1.5mg/kg) of amphetamine, but with a lower dose. Ovariectomized female rats received 5μg of estradiol benzoate (EB) or OIL 30min before each of 5 treatments of 1.0mg/kg amphetamine or saline; all received a 0.5mg/kg challenge dose three days later. Compared with results for OIL, EB enhanced the locomotor-activating effects of repeated 1.0mg/kg amphetamine across treatment days. In contrast, on challenge day, there was no difference between EB-saline and EB-amphetamine to the lower dose (i.e., no sensitization). Experiments 2 and 3 involved a shorter induction (2days) and a lengthier withdrawal (9days) before the challenge test for the expression of sensitization to better differentiate the induction phase from the expression phase. In Expt2, EB-, and not OIL-, treated rats showed sensitization to 0.5mg/kg amphetamine; neither group showed sensitization to 1.5mg/kg amphetamine (ceiling effect?). In Expt3, rats were treated with EB either in both the induction and expression phases, in one of the phases only, or in neither phase. There was an effect of hormone treatment on challenge day and not on induction day; rats given EB on Challenge day showed sensitization to 0.5mg/kg amphetamine; OIL rats did

The lowest-dose, extended-cycle combined oral contraceptive pill with continuous ethinyl estradiol in the United States: a review of the literature on ethinyl estradiol 20 μg/levonorgestrel 100 μg + ethinyl estradiol 10 μg.

PubMed

Krishnan, Sheila; Kiley, Jessica

2010-08-10

Extended-cycle oral contraceptives (OCs) are increasing in popularity in the United States. A new extended-cycle OC that contains the lowest doses of ethinyl estradiol (EE) and levonorgestrel (LNG) + continuous EE throughout the cycle is now available. It provides 84 days of a low-dose, combined active pill containing levonorgestrel 100 μg and ethinyl estradiol 20 μg. Instead of 7 days of placebo following the active pills, the regimen delivers 7 days of ethinyl estradiol 10 μg. Existing studies reveal a similar efficacy and adverse effect profile compared with other extended-regimen OCs. Specifically, the unscheduled bleeding profile is similar to other extended-cycle OCs and improves with the increase in the duration of use. Although lower daily doses of hormonal exposure have potential benefit, to our knowledge, there are no published studies indicating that this specific regimen offers a lower incidence of hormone-related side effects or adverse events. In summary, this new extended-cycle OC provides patients a low-dose, extended-regimen OC option without sacrificing efficacy or tolerability.

Effects of preovulatory estradiol on embryo survival and pregnancy establishment in beef cows

USDA-ARS?s Scientific Manuscript database

The role of preovulatory estradiol on embryo survival and pregnancy establishment has not been well characterized in beef cows. We hypothesized that preovulatory estradiol is important for embryo survival and pregnancy establishment in beef cows. Twenty-four ovariectomized multiparous cows were use...

Estradiol to testosterone ratio in metabolic syndrome men aged started 40 years above

NASA Astrophysics Data System (ADS)

Kusuma, R.; Siregar, Y.; Mardianto

2018-03-01

Disruption of adipose tissue, an endocrine organ, could turn out into the so-called metabolic syndrome. Aging men with lowering testosterone were related to metabolic syndrome and excessive aromatase activity in adipose tissue would increase estradiol level. This study hypothesized that estradiol to testosterone ratio is increasedin aging, metabolic syndrome men. A total of 52 men were randomly recruited for this study. A blood samplewas drawn before 11.00 AM after 10 hoursof overnight fasting, then aliquot serum kept in -20°C pending the research. Subjects were divided evenly into the metabolic syndrome and nonmetabolicsyndrome group. The hormonal assaywas measured on the day of research. Then examined with student t-test. Estradiol level in metabolic syndrome group was increased, but insignificant differ to the other group. Testosterone level decreased and significantly different between groups. In conclusion, estradiol to testosterone ratio was increased in themetabolic syndrome group but insignificant.

Bioaccumulation profiles of polychlorinated biphenyl congeners and organochlorine pesticides in Ganges River dolphins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Senthilkumar, K.; Kannan, K.; Sinha, R.K.

1999-07-01

Isomer-specific concentrations of polychlorinated biphenyls (PCBs) including non-, mono-, and di-ortho-substituted congeners, DDT and its metabolites, hexachlorocyclohexane (HCH) isomers, chlordane compounds, and hexachlorobenzene (HCB) were determined in river dolphin blubber and prey fishes collected during 1993 through 1996 from the River Ganges in India. Concentrations of organochlorines were also measured in the milk and liver of dolphins, benthic invertebrates, and sediments. The DDTs and PCBs were the predominant compounds found in dolphin tissues and fish that comprise the diet of dolphins. Concentrations of DDTs and PCBs in the blubber of dolphins were in the range of 30 to 120 andmore » 1.5 to 25 {micro}g/g, lipid weight, respectively. Penta- and hexachlorobiphenyls collectively accounted for 68 to 80% of the total PCB concentrations in river dolphins. Hexachlorobiphenyl congener 138 (2.2{prime}, 3,4,4{prime},5{prime}-) was the most abundant in dolphin blubber and prey fishes. The isomer/congener pattern of PCBs and organchlorine pesticides suggested that there is less metabolism due to cytochrome P450 enzymes in Ganges river dolphins than in marine or terrestrial mammals. The mean 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) estimated in river dolphin blubber was greater than those that can cause adverse effects in mink. Comparison of organochlorine concentrations in river dolphins with those of the values reported for samples analyzed during 1988 through 1992 suggested that the contamination by these compounds has increased in the River Ganges.« less

Changes in salivary estradiol predict changes in women's preferences for vocal masculinity.

PubMed

Pisanski, Katarzyna; Hahn, Amanda C; Fisher, Claire I; DeBruine, Lisa M; Feinberg, David R; Jones, Benedict C

2014-08-01

Although many studies have reported that women's preferences for masculine physical characteristics in men change systematically during the menstrual cycle, the hormonal mechanisms underpinning these changes are currently poorly understood. Previous studies investigating the relationships between measured hormone levels and women's masculinity preferences tested only judgments of men's facial attractiveness. Results of these studies suggested that preferences for masculine characteristics in men's faces were related to either women's estradiol or testosterone levels. To investigate the hormonal correlates of within-woman variation in masculinity preferences further, here we measured 62 women's salivary estradiol, progesterone, and testosterone levels and their preferences for masculine characteristics in men's voices in five weekly test sessions. Multilevel modeling of these data showed that changes in salivary estradiol were the best predictor of changes in women's preferences for vocal masculinity. These results complement other recent research implicating estradiol in women's mate preferences, attention to courtship signals, sexual motivation, and sexual strategies, and are the first to link women's voice preferences directly to measured hormone levels. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative effects of estradiol, methyl-piperidino-pyrazole, raloxifene, and ICI 182 780 on gene expression in the murine uterus.

PubMed

Davis, Angela M; Mao, Jiude; Naz, Bushra; Kohl, Jessica A; Rosenfeld, Cheryl S

2008-10-01

Selective estrogen receptor modulators (SERMs) are potentially useful in treating various endometrial disorders, including endometrial cancer, as they block some of the detrimental effects of estrogen. It remains unclear whether each SERM regulates a unique subset of genes and, if so, whether the combination of a SERM and 17beta-estradiol has an additive or synergistic effect on gene expression. We performed microarray analysis with Affymetrix Mouse Genome 430 2.0 short oligomer arrays to determine gene expression changes in uteri of ovariectomized mice treated with estradiol (low and high dose), methyl-piperidino-pyrazole (MPP), ICI 182 780, raloxifene, and combinations of high dose of estradiol with one of the SERM and dimethyl sulfoxide (DMSO) vehicle control. The nine treatments clustered into two groups, with MPP, raloxifene, and high dose of estradiol in one, and low dose of estradiol, ICI + estradiol, ICI, MPP + estradiol, and raloxifene + estradiol in the second group. Surprisingly, combining a high dose of estradiol with a SERM markedly increased (P<0.02) the number of regulated genes compared with each individual treatment. Analysis of expression for selected genes in uteri of estradiol and SERM-treated mice by quantitative (Q)RT-PCR generally supported the microarray results. For some cancer-associated genes, including Klk1, Ihh, Cdc45l, and Cdca8, administration of MPP or raloxifene with estradiol resulted in greater expression than estradiol alone (P<0.05). By contrast, ICI 182 780 suppressed more genes governing DNA replication compared with MPP and raloxifene treatments. Therefore, ICI 182 780 might be superior to MPP and raloxifene to treat estrogen-induced endometrial cancer in women.

Identification of indicator congeners and evaluation of emission pattern of polychlorinated naphthalenes in industrial stack gas emissions by statistical analyses.

PubMed

Liu, Guorui; Cai, Zongwei; Zheng, Minghui; Jiang, Xiaoxu; Nie, Zhiqiang; Wang, Mei

2015-01-01

Identifying marker congeners of unintentionally produced polychlorinated naphthalenes (PCNs) from industrial thermal sources might be useful for predicting total PCN (∑2-8PCN) emissions by the determination of only indicator congeners. In this study, potential indicator congeners were identified based on the PCN data in 122 stack gas samples from over 60 plants involved in more than ten industrial thermal sources reported in our previous case studies. Linear regression analyses identified that the concentrations of CN27/30, CN52/60, and CN66/67 correlated significantly with ∑2-8PCN (R(2)=0.77, 0.80, and 0.58, respectively; n=122, p<0.05), which might be good candidates for indicator congeners. Equations describing relationships between indicators and ∑2-8PCN were established. The linear regression analyses involving 122 samples showed that the relationships between the indicator congeners and ∑2-8PCN were not significantly affected by factors such as industry types, raw materials used, or operating conditions. Hierarchical cluster analysis and similarity calculations for the 122 stack gas samples were adopted to group those samples and evaluating their similarity and difference based on the PCN homolog distributions from different industrial thermal sources. Generally, the fractions of less chlorinated homologs comprised of di-, tri-, and tetra-homologs were much higher than that of more chlorinated homologs for up to 111 stack gas samples contained in group 1 and 2, which indicating the dominance of lower chlorinated homologs in stack gas from industrial thermal sources. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemometric comparison of polychlorinated biphenyl residues and toxicologically active polychlorinated biphenyl congeners in the eggs of Forster's Terns (Sterna fosteri)

USGS Publications Warehouse

Schwartz, Ted R.; Stalling, David L.

1991-01-01

The separation and characterization of complex mixtures of polychlorinated biphenyls (PCBs) is approached from the perspective of a problem in chemometrics. A technique for quantitative determination of PCB congeners is described as well as an enrichment technique designed to isolate only those congener residues which induce mixed aryl hydrocarbon hydroxylase enzyme activity. A congener-specific procedure is utilized for the determination of PCBs in whichn-alkyl trichloroacetates are used as retention index marker compounds. Retention indices are reproducible in the range of ±0.05 to ±0.7 depending on the specific congener. A laboratory data base system developed to aid in the editing and quantitation of data generated from capillary gas chromatography was employed to quantitate chromatographic data. Data base management was provided by computer programs written in VAX-DSM (Digital Standard MUMPS) for the VAX-DEC (Digital Equipment Corp.) family of computers.In the chemometric evaluation of these complex chromatographic profiles, data are viewed from a single analysis as a point in multi-dimensional space. Principal Components Analysis was used to obtain a representation of the data in a lower dimensional space. Two-and three-dimensional proections based on sample scores from the principal components models were used to visualize the behavior of Aroclor® mixtures. These models can be used to determine if new sample profiles may be represented by Aroclor profiles. Concentrations of individual congeners of a given chlorine substitution may be summed to form homologue concentration. However, the use of homologue concentrations in classification studies with environmental samples can lead to erroneous conclusions about sample similarity. Chemometric applications are discussed for evaluation of Aroclor mixture analysis and compositional description of environmental residues of PCBs in eggs of Forster's terns (Sterna fosteri) collected from colonies near Lake Poygan

Estradiol induces endothelial cell migration and proliferation through estrogen receptor-enhanced RhoA/ROCK pathway.

PubMed

Oviedo, Pilar J; Sobrino, Agua; Laguna-Fernandez, Andrés; Novella, Susana; Tarín, Juan J; García-Pérez, Miguel-Angel; Sanchís, Juan; Cano, Antonio; Hermenegildo, Carlos

2011-03-30

Migration and proliferation of endothelial cells are involved in re-endothelialization and angiogenesis, two important cardiovascular processes that are increased in response to estrogens. RhoA, a small GTPase which controls multiple cellular processes, is involved in the control of cell migration and proliferation. Our aim was to study the role of RhoA on estradiol-induced migration and proliferation and its dependence on estrogen receptors activity. Human umbilical vein endothelial cells were stimulated with estradiol, in the presence or absence of ICI 182780 (estrogen receptors antagonist) and Y-27632 (Rho kinase inhibitor). Estradiol increased Rho GEF-1 gene expression and RhoA (gene and protein expression and activity) in an estrogen receptor-dependent manner. Cell migration, stress fiber formation and cell proliferation were increased in response to estradiol and were also dependent on the estrogen receptors and RhoA activation. Estradiol decreased p27 levels, and significantly raised the expression of cyclins and CDK. These effects were counteracted by the use of either ICI 182780 or Y-27632. In conclusion, estradiol enhances the RhoA/ROCK pathway and increases cell cycle-related protein expression by acting through estrogen receptors. This results in an enhanced migration and proliferation of endothelial cells. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Congener-specific determination of ultratrace levels of chlorinated and brominated polycyclic aromatic hydrocarbons in atmosphere and industrial stack gas by isotopic dilution gas chromatography/high resolution mass spectrometry method.

PubMed

Jin, Rong; Liu, Guorui; Zheng, Minghui; Fiedler, Heidelore; Jiang, Xiaoxu; Yang, Lili; Wu, Xiaolin; Xu, Yang

2017-08-04

Isotopic dilution gas chromatography combined with high resolution mass spectrometry (GC/HRMS) has overwhelming advantages with respect to the accuracy of congener-specific ultratrace analysis of complex persistent organic pollutants (POPs) in environmental matrices. However, an isotopic dilution GC/HRMS method for analysis of chlorinated and brominated polycyclic aromatic hydrocarbons (Cl-PAHs and Br-PAHs) using 13 C-labelled congeners as internal standards has not been established. In this study, a method for identification and quantification of 38 congeners of Cl-PAHs and Br-PAHs in atmosphere and stack gas samples from waste incinerators was developed using the isotopic dilution GC/HRMS technique. The instrumental detection limits of the GC/HRMS method ranged from 0.2pg to 1.8pg for Cl-PAH congeners, and 0.7pg to 2.7pg for Br-PAH congeners, which were about three orders of magnitude lower than those of the GC/quadrupole MS method. This new method developed was also the first to enable determination of Cl-PAH and Br-PAH homologs comprising congeners with the same molecular skeleton and chlorine or bromine substitution numbers. Among the detected congeners, seven Cl-PAH congeners and thirteen Br-PAH congeners that were abundant in the atmosphere and stack gases released from waste incinerators were firstly detected in real samples and reported using the established isotopic dilution GC/HRMS method. The developed isotopic dilution GC/HRMS is significant and needed for better studying the environmental behavior and health risk of Cl-PAHs and Br-PAHs. Copyright © 2017 Elsevier B.V. All rights reserved.

An invasive plant alters phenotypic selection on the vegetative growth of a native congener.

PubMed

Beans, Carolyn M; Roach, Deborah A

2015-02-01

The ecological consequences of plant competition have frequently been tested, but the evolutionary outcomes of these interactions have gone largely unexplored. The study of species invasions can make an important contribution to this field of research by allowing us to watch ecological and evolutionary processes unfold as a novel species is integrated into a plant community. We explored the ecological and evolutionary impact of an invasive jewelweed, Impatiens glandulifera, on a closely related native congener, I. capensis and asked: (1) Does the presence of the invasive jewelweed alter the fitness of native jewelweed populations? (2) Does the invasive jewelweed affect the vegetative growth of the native congener? and (3) Does the invasive jewelweed alter phenotypic selection on the vegetative traits of the native congener? We used a greenhouse competition experiment, an invasive species removal field experiment, and a survey of natural populations. We show that when the invasive jewelweed is present, phenotypic selection favors native jewelweed individuals investing less in rapid upward growth and more in branching and fruiting potential through the production of nodes. This research demonstrates that invasive plants have the potential to greatly alter natural selection on native competitors. Studies investigating altered selection in invaded communities can reveal the potential evolutionary impact of invasive competitors, while deepening our understanding of the more general role of competition in driving plant evolution and permitting species coexistence. © 2015 Botanical Society of America, Inc.

The crystallogenesis of a human estradiol dehydrogenase-substrate complex

NASA Astrophysics Data System (ADS)

Zhu, Dao-Wei; Azzi, Arezki; Rehse, Peter; Lin, Sheng-Xiang

1996-10-01

Human 17β-hydroxysteroid dehydrogenase type 1 is an important steroidogenic enzyme catalyzing the synthesis of the most active estrogen: estradiol. The enzyme is formed by two identical subunits (34.5 kDa). In this paper, we report the preparation of a stoichiometric 17β-HSD1-estradiol complex sample at a much higher concentration than the solubility of the free substrate, using a gradual concentration of the enzyme-substrate mixture starting at low concentration. The complex is successfully crystallized by vapor diffusion at pH 7.5 with polyethyleneglycol 4000 as the precipitating agent. The space group is C2 with a = 123.56 Å, b = 45.21 Å, c = 61.30 Å and β = 99.06°. There is one monomer in the asymmetric unit and two molecules of the enzyme in a unit cell. A diffraction data set to 2.5 Å has been collected to 86% completeness on native crystals. The high quality of the electronic density map of estradiol supports the full occupancy of the binding site, thus confirming the efficiency of the complex preparation. This method will also be useful in crystallizing other steroid-dehydrogenase complexes.

Fractionation and current time trends of PCB congeners: evolvement of distributions 1950-2010 studied using a global atmosphere-ocean general circulation model

NASA Astrophysics Data System (ADS)

Lammel, G.; Stemmler, I.

2012-08-01

PCBs are ubiquitous environmental pollutants expected to decline in abiotic environmental media in response to decreasing primary emissions since the 1970s. A coupled atmosphere-ocean general circulation model with embedded dynamic sub-models for atmospheric aerosols and the marine biogeochemistry and air-surface exchange processes with soils, vegetation and the cryosphere is used to study the transport and fate of four PCB congeners covering a range of 3-7 chlorine atoms. The change of the geographic distribution of the PCB mixture reflects the sources and sinks' evolvement over time. Globally, secondary emissions (re-volatilisation from surfaces) are on the long term increasingly gaining importance over primary emissions. Secondary emissions are most important for the congeners with 5-6 chlorine atoms. Correspondingly, the levels of these congeners are predicted to decrease slowest. Changes in congener mixture composition (fractionation) are characterized both geographically and temporally. In high latitudes enrichment of the lighter, less persistent congeners and more delayed decreasing levels in response to decreasing emissions are found. The delivery of the contaminants to high latitudes is predicted to be more efficient than previously suggested. The results suggest furthermore that the effectiveness of emission control measures may significantly vary among substances. The trends of decline of organic contaminant levels in the abiotic environmental media do not only vary with latitude (slow in high latitudes), but do also show longitudinal gradients.

[Influence of the high peak serum estradiol on the outcome of in vitro fertilization cycles].

PubMed

Carmona-Ruiz, Israel Obed; Galache-Vega, Pedro; Santos-Haliscak, Roberto; Díaz-Spíndola, Pablo; Batiza-Reséndiz, Víctor Alfonso; Hernández-Ayup, Samuel

2010-10-01

For the use of assisted reproductive technologies of high complexity (IVF-ET and ICSI) is essential to proper ovarian stimulation with recombinant FSH drugs menotropins, as well as the use of GnRH analogues. To correlate serum estradiol level on day 10th with the outcome of in vitro fertilization cycles. Retrospective study of 523 IVF cycles, selected and analyzed from 2005 to 2009. Patients underwent individualized stimulation protocols with gonadotropins and agonist (late luteal phase). The patients were divided into three groups according with the serum level of estradiol on day 10th of stimulation: Group I, patients with serum level of Estradiol below 1,000 pg/mL; Group II, with levels between 1,000-4,000 pg/mL; and Group III, with levels above 4,000 pg/mL. Peak serum estradiol levels, oocyte number, fertilization rates, implantation rates, and pregnancy rates were compared among groups. The fertilization rate was 62.8 in Group I; 60.6% in Group II, and 54.2% in Group III. The pregnancy rate in Group I was 29.8%; in Group II, 37.3%; and 24% for Group III. The implantation rates were 14, 22 and 14% for each group respectively (I, II and III). There is an inverse relationship between high peak serum estradiol levels and pregnancy rate; the implantation rate seems affected by the extreme levels of serum estradiol. The percent of total mature oocytes and fertilization rate improve with serum levels of estradiol at physiologic values.

Higher than expected estradiol levels in aromatase inhibitor-treated, postmenopausal breast cancer patients.

PubMed

Kunovac Kallak, T; Baumgart, J; Stavreus Evers, A; Sundström Poromaa, I; Moby, L; Kask, K; Norjavaara, E; Kushnir, M M; Bergquist, J; Nilsson, K

2012-10-01

Vaginal estradiol is considered contraindicated in aromatase inhibitor (AI)-treated patients because of the risk of elevated estrogen levels. This leaves limited treatment options for patients experiencing gynecological symptoms. However, in clinical practice, no precise estimation has been performed of circulating estrogens and aromatase index in postmenopausal breast cancer patients on long-lasting AI or tamoxifen treatment. Steroid hormones were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) and extraction radioimmunoassay (RIA). Postmenopausal AI-treated patients (n =33) were compared with tamoxifen-treated patients (n =34) and controls without vaginal treatment (n =56), with vaginal estradiol (n =25), or with estriol (n =11) treatment. By use of LC-MS/MS, median (range) estradiol plasma concentrations were 16.7 (2.4-162.6), 31.0 (13.4-77.1), 27.2 (7.8-115.8) and 33.3 (20.3-340.1) pmol/l in AI-treated breast cancer patients, tamoxifen-treated breast cancer patients, postmenopausal controls and postmenopausal controls on vaginal estradiol, respectively. The AI-treated group and subgroups had significantly lower estradiol and estrone concentrations than all other groups (p <0.05). There was extensive interindividual variation in estradiol concentration within the AI-treated group, measured using both LC-MS/MS (2.3-182.0 pmol/l) and extraction RIA (2.4-162.6 pmol/l). The AI-treated group had lower aromatase index compared to all other groups (p <0.05-0.001). Circulating estrogen levels may have been underestimated in previous longitudinal studies of AI-treated breast cancer patients. Additional studies are required to further evaluate the role of circulating estrogens in breast cancer patients suffering from gynecological symptoms.

Relation among cytochrome P450, AH-active PCB congeners and dioxin equivalents in pipping black-crowned night-heron embryos

USGS Publications Warehouse

Rattner, B.A.; Hatfield, J.S.; Melancon, M.J.; Custer, T.W.; Tillitt, D.E.

1994-01-01

Pipping black-crowned night-heron (Nycticorax nycticorax) embryos were collected from a relatively uncontaminated site (next to Chincoteague National Wildlife Refuge, VA) and three polluted sites (Cat Island, Green Bay, Lake Michigan, WI; Bair Island, San Francisco Bay, CA; West Marin Island, San Francisco Bay, CA). Hepatic cytochrome P-450-associated monooxygenases and cytochrome P-450 proteins, induced up to 85-fold relative to the reference site, were associated with concentrations of total polychlorinated biphenyls (PCBs) and 11 PCB congeners that are presumed to express toxicity through the arylhydrocarbon (Ah) receptor. Multiple regression revealed that up to 86% of the variation of cytochrome P450 measurements was accounted for by variation in the concentration of these PCB congeners. Toxic equivalents (TEQs) of sample extracts, predicted mathematically (summed product of PCB congener concentrations and toxic equivalency factors), and dioxin equivalents (TCDD-EQs), derived by bioassay (ethoxyresorufin-O-dealkylase activity of treated H4IIE rat hepatoma cells), were greatest in Cat Island samples. Cytochrome P450-associated monooxygenases and cytochrome P450 proteins were related to TEQs and TCDD-EQs; adjusted r-2 often exceeded 0.5 for the relation among mathematically predicted TEQs and cytochrome P450 measurements. These data extend previous observations in heron embryos of an association between P450 and total PCB burdens to include Ah-active PCB congeners, and presumably other compounds, which interact similarly with the Ah receptor. Benzyloxyresorufin O-dealkylase, ethoxyresorufin O-dealkylase, and cytochrome P450 1A appear to be the most reliable measures of exposure to Ah-active PCB congeners in black-crowned night-heron embryos. These findings provide further evidence that cytochrome P450-associated parameters have considerable value as a biomarker for assessing environmental contamination of wetlands.

Determination of estradiol valerate in pharmaceutical preparations and human serum by flow injection chemiluminescence.

PubMed

Liu, Wenwen; Xie, Liangxiao; Liu, Hongshuang; Xu, Shichao; Hu, Bingcheng; Cao, Wei

2013-01-01

A novel method for the detection of trace estradiol valerate (EV) in pharmaceutical preparations and human serum was developed by inhibition of luminol chemiluminescence (CL) by estradiol valerate on the zinc deuteroporphyrin (ZnDP)-enhanced luminol-K3 Fe(CN)6 chemiluminescence system. Under optimized experimental conditions, CL intensity and concentration of estradiol valerate had a good linear relationship in the ranges of 8.0 × 10(-8) to 1.0 × 10(-5) g/mL. Detection limit (3σ) was estimated to be 3.5 × 10(-8) g/mL. The proposed method was applied successfully for the determination of estradiol valerate in pharmaceutical preparations and human serum and recoveries were 97.0-105.0% and 95.5-106.0%, respectively. The possible mechanism of the CL system is discussed. Copyright © 2012 John Wiley & Sons, Ltd.

Ovariectomy and 17β-estradiol replacement in rats and mice: a visual demonstration.

PubMed

Ström, Jakob O; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

2012-06-07

Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures.

Evolution of body shape in differently coloured sympatric congeners and allopatric populations of Lake Malawi's rock-dwelling cichlids.

PubMed

Husemann, M; Tobler, M; McCauley, C; Ding, B; Danley, P D

2014-05-01

The cichlid fishes of Lake Malawi represent one of the most diverse adaptive radiations of vertebrates known. Among the rock-dwelling cichlids (mbuna), closely related sympatric congeners possess similar trophic morphologies (i.e. cranial and jaw structures), defend overlapping or adjacent territories, but can be easily distinguished based on male nuptial coloration. The apparent morphological similarity of congeners, however, leads to an ecological conundrum: theory predicts that ecological competition should lead to competitive exclusion. Hence, we hypothesized that slight, yet significant, ecological differences accompanied the divergence in sexual signals and that the divergence of ecological and sexual traits is correlated. To evaluate this hypothesis, we quantified body shape, a trait of known ecological importance, in populations of Maylandia zebra, a barred, widespread mbuna, and several sympatric nonbarred congeners. We found that the barred populations differ in body shape from their nonbarred sympatric congeners and that the direction of shape differences was consistent across all barred vs. nonbarred comparisons. Barred populations are generally deeper bodied which may be an adaptation to the structurally complex habitat they prefer, whereas the nonbarred species have a more fusiform body shape, which may be adaptive in their more open microhabitat. Furthermore, M. zebra populations sympatric with nonbarred congeners differ from populations where the nonbarred phenotype is absent and occupy less morphospace, indicating potential ecological character displacement. Mitochondrial DNA as well as published AFLP data indicated that the nonbarred populations are not monophyletic and therefore may have evolved multiple times independently. Overall our data suggest that the evolution of coloration and body shape may be coupled as a result of correlational selection. We hypothesize that correlated evolution of sexually selected and ecological traits may have

DIFFERENTIAL EFFECTS OF TWO LOTS OF AROCLOR 1254R: CONGENER ANALYSIS AND NEUROCHEMICAL ENDPOINTS.

EPA Science Inventory

Introduction
Polychlorinated biphenyls (PCBs) are widely used in industry as heat transfer and dielectric fluids for transformers and capacitors1. PCBs were commercially produced as AroclorR mixtures in USA by the chlorination of biphenyl. Although all 209 congeners can be syn...

Effects of oral exposure to naturally-occurring and synthetic deoxynivalenol congeners on proinflammatory cytokine and chemokine mRNA expression in the mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Wenda; Dept. of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824; He, Kaiyu

The foodborne mycotoxin deoxynivalenol (DON) induces a ribotoxic stress response in mononuclear phagocytes that mediate aberrant multi-organ upregulation of TNF-α, interleukins and chemokines in experimental animals. While other DON congeners also exist as food contaminants or pharmacologically-active derivatives, it is not known how these compounds affect expression of these cytokine genes in vivo. To address this gap, we compared in mice the acute effects of oral DON exposure to that of seven relevant congeners on splenic expression of representative cytokine mRNAs after 2 and 6 h. Congeners included the 8-ketotrichothecenes 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), nivalenol (NIV), themore » plant metabolite DON-3-glucoside (D3G) and two synthetic DON derivatives with novel satiety-inducing properties (EN139528 and EN139544). DON markedly induced transient upregulation of TNF-α IL-1β, IL-6, CXCL-2, CCL-2 and CCL-7 mRNA expressions. The two ADONs also evoked mRNA expression of these genes but to a relatively lesser extent. FX induced more persistent responses than the other DON congeners and, compared to DON, was: 1) more potent in inducing IL-1β mRNA, 2) approximately equipotent in the induction of TNF-α and CCL-2 mRNAs, and 3) less potent at upregulating IL-6, CXCL-2, and CCL-2 mRNAs. EN139528's effects were similar to NIV, the least potent 8-ketotrichothecene, while D3G and EN139544 were largely incapable of eliciting cytokine or chemokine mRNA responses. Taken together, the results presented herein provide important new insights into the potential of naturally-occurring and synthetic DON congeners to elicit aberrant mRNA upregulation of cytokines associated with acute and chronic trichothecene toxicity. - Highlights: • We compared effects of DON congeners on biomarker proinflammatory genes in mice. • Oral DON induced splenic IL-1β, IL-6, TNF-α,CXCL-2, CCL-2 and CCL-7 mRNAs. • 8-Ketotrichothecene

Precipitation scavenging of polychlorinated biphenyl congeners in the great lakes region

NASA Astrophysics Data System (ADS)

Murray, Michael W.; Andren, Anders W.

Ten precipitation events were sampled in the fall of 1986 in Madison, WI and analyzed for individual congener and total polychlorinated biphenyl (PCB) levels in both the dissolved and particulate phases. Total PCB concentrations were generally at the lower end of ranges recently reported for precipitation. Operationally defined dissolved and particulate phase congener distribution patterns for the two events of highest concentration were qualitatively similar to gas-phase and particle-bound patterns for northern Wisconsin air samples. Higher than predicted dissolved-phase concentrations may indicate non-equilibrium processes during scavenging and/or sample processing, the presence of colloids and micro-particulates, and/or more efficient gas-phase transfer to hydrometeors with organic coatings. Observed organic carbon-normalized distribution coefficients increased slightly with increasing octanol-water partition coefficient, giving the relationship log Koc = 0.22 log Kow + 4.64. The data indicate that a third organic-rich colloidal phase could be influencing partitioning, and could explain the higher than expected apparent gas scavenging efficiency for PCBs from the atmosphere. Precipitation-weighted mean fluxes of PCBs in the dissolved and particulate phases were 1.2 and 1.4 μg m -2 year -1, respectively, indicating that precipitation remains a significant source of PCBs to the upper Great Lakes.

Estradiol treatment in preadolescent females enhances adolescent spatial memory and differentially modulates hippocampal region-specific phosphorylated ERK labeling.

PubMed

Wartman, Brianne C; Keeley, Robin J; Holahan, Matthew R

2012-10-24

Estrogen levels in rats are positively correlated with enhanced memory function and hippocampal dendritic spine density. There is much less work on the long-term effects of estradiol manipulation in preadolescent rats. The present work examined how injections of estradiol during postnatal days 19-22 (p19-22; preadolescence) affected water maze performance and hippocampal phosphorylated ERK labeling. To investigate this, half of the estradiol- and vehicle-treated female rats were trained on a water maze task 24h after the end of estradiol treatment (p23-27) while the other half was not trained. All female rats were tested on the water maze from p40 to p44 (adolescence) and hippocampal pERK1/2 labeling was assessed as a putative marker of neuronal plasticity. During adolescence, preadolescent-trained groups showed lower latencies than groups without preadolescent training. Retention data revealed lower latencies in both estradiol groups, whether preadolescent trained or not. Immunohistochemical detection of hippocampal pERK1/2 revealed elevations in granule cell labeling associated with the preadolescent trained groups and reductions in CA1 labeling associated with estradiol treatment. These results show a latent beneficial effect of preadolescent estradiol treatment on adolescent spatial performance and suggest an organizational effect of prepubescent exogenously applied estradiol. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Metabolic clearance and blood production rates of estradiol in hyperthyroidism.

PubMed

Ridgway, E C; Longcope, C; Maloof, F

1975-09-01

The metabolic clearance rate of 17beta-estradiol (MCR2), the plasma levels of 17beta-estradiol (E2)1, sex-steroid binding globulin (SSBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in 10 hyperthyroid subjects (7 men and 3 women). The blood production rate of 17beta-estradiol (PB2) was calculated for all subjects. Nine of the 10 hyperthyroid subjects had a decreased MCR2 which returned towards normal in 5 of the 6 subjects restudied following therapy. In all 10 subjects the levels of SSBG were increased when they were hyperthyroid and returned toward normal with therapy. It is concluded that the decrease in MCR2 is largely due to the increased binding of 17beta-estradiol to SSBG. In 7 of the 10 hyperthyroid the plasma E2 concentrations were normal whereas 3 had slightly elevated levels. In 8 of the 10 hyperthyroid the PB2 was within the normal range. Only 2 hyperthyroid subjects had slightly elevated PB2. In the 6 subjects who were restudied after therapy, there was no consistent change in PB2 which remained in the normal range in all cases. It is concluded that the MCR2 is decreased in most subjects with hyperthyroidism in association with an increase of SSBG. Despite this change in MCR2 there is no significant change in PB2. The increase in SSBG levels in hyperthyroidism appears to be a direct effect of the elevation of thyroid hormone activity and is not mediated through estrogen.

Effects of preovulatory estradiol concentration on embryo survival and pregnancy establishment in beef cows

USDA-ARS?s Scientific Manuscript database

The role of estradiol during the preovulatory period on embryo survival and pregnancy establishment has not been characterized in beef cows. We hypothesized that preovulatory estradiol is important for embryo survival and pregnancy establishment in beef cows. In order to establish the importance o...

Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies.

PubMed

Wise, P M; Dubal, D B; Wilson, M E; Rau, S W; Böttner, M; Rosewell, K L

2001-11-01

We have shown that 17beta-estradiol exerts profound protective effects against stroke-like ischemic injury in female rats. These effects are evident using physiological levels of estradiol replacement in ovariectomized rats and require hormone treatment prior to the time of injury. The protective actions of estradiol appear to be most prominent in the cerebral cortex, where cell death is not apparent until at least 4 h after the initiation of ischemic injury and where cell death is thought to be apoptotic in nature. Middle-aged rats remain equally responsive to the protective actions of estradiol. The maintenance of responsiveness of the cerebral cortex to the neuroprotective actions of estradiol was unexpected since responsiveness of the hypothalamus to estradiol decreases dramatically by the time animals are middle-aged. We believe that the protective actions of estradiol require the estrogen receptor-alpha, since estradiol does not protect in estrogen receptor-alpha knockout mice. We have also implemented a method of culturing cerebral cortical explants to assess the protective effects of estradiol in vitro. This model exhibits remarkable parallelisms with our in vivo model of brain injury. We have found that 17beta-estradiol decreases the extent of cell death and that this protective effect requires hormone pretreatment. Finally, 17alpha-estradiol, which does not interact effectively with the estrogen receptor, does not protect; and addition of ICI 182,780, an estrogen receptor antagonist, blocks the protective actions of estradiol. We have begun to explore the molecular and cellular mechanisms of estradiol-mediated protection. In summary, our findings demonstrate that estradiol exerts powerful protective effects both in vivo and in vitro and suggest that these actions are mediated by estrogen receptors.

Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection

NASA Astrophysics Data System (ADS)

Xu, Yun; Zhang, Wenri; Klaus, Judith; Young, Jennifer; Koerner, Ines; Sheldahl, Laird C.; Hurn, Patricia D.; Martínez-Murillo, Francisco; Alkayed, Nabil J.

2006-09-01

Estrogen reduces brain injury after experimental cerebral ischemia in part through a genomic mechanism of action. Using DNA microarrays, we analyzed the genomic response of the brain to estradiol, and we identified a transcript, cocaine- and amphetamine-regulated transcript (CART), that is highly induced in the cerebral cortex by estradiol under ischemic conditions. Using in vitro and in vivo models of neural injury, we confirmed and characterized CART mRNA and protein up-regulation by estradiol in surviving neurons, and we demonstrated that i.v. administration of a rat CART peptide is protective against ischemic brain injury in vivo. We further demonstrated binding of cAMP response element (CRE)-binding protein to a CART promoter CRE site in ischemic brain and rapid activation by CART of ERK in primary cultured cortical neurons. The findings suggest that CART is an important player in estrogen-mediated neuroprotection and a potential therapeutic agent for stroke and other neurodegenerative diseases. ischemia | stroke | estrogen

Maternal fructose intake disturbs ovarian estradiol synthesis in rats.

PubMed

Munetsuna, Eiji; Yamada, Hiroya; Yamazaki, Mirai; Ando, Yoshitaka; Mizuno, Genki; Ota, Takeru; Hattori, Yuji; Sadamoto, Nao; Suzuki, Koji; Ishikawa, Hiroaki; Hashimoto, Shuji; Ohashi, Koji

2018-06-01

Recent increases in fructose consumption have raised concerns regarding the potential adverse intergenerational effects, as maternal fructose intake may induce physiological dysfunction in offspring. However, no reports are available regarding the effect of excess maternal fructose on reproductive tissues such as the ovary. Notably, the maternal intrauterine environment has been demonstrated to affect ovarian development in the subsequent generation. Given the fructose is transferred to the fetus, excess fructose consumption may affect offspring ovarian development. As ovarian development and its function is maintained by 17β-estradiol, we therefore investigated whether excess maternal fructose intake influences offspring ovarian estradiol synthesis. Rats received a 20% fructose solution during gestation and lactation. After weaning, offspring ovaries were isolated. Offspring from fructose-fed dams showed reduced StAR and P450(17α) mRNA levels, along with decreased protein expression levels. Conversely, attenuated P450arom protein level was found in the absence of mRNA expression alteration. Consistent with these phenomena, decreased circulating levels of estradiol were observed. Furthermore, estrogen receptor α (ERα) protein levels were also down-regulated. In accordance, the mRNA for progesterone receptor, a transcriptional target of ERα, was decreased. These results suggest that maternal fructose might alter ovarian physiology in the subsequent generation. Copyright © 2018 Elsevier Inc. All rights reserved.

21 CFR 862.1260 - Estradiol test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... treatment of various hormonal sexual disorders and in assessing placental function in complicated pregnancy...

21 CFR 862.1260 - Estradiol test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

21 CFR 862.1260 - Estradiol test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

21 CFR 862.1260 - Estradiol test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

21 CFR 862.1260 - Estradiol test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

Physical activity and sex hormone levels in estradiol- and placebo-treated postmenopausal women.

PubMed

Choudhury, Farzana; Bernstein, Leslie; Hodis, Howard N; Stanczyk, Frank Z; Mack, Wendy J

2011-10-01

Postmenopausal changes in the hormonal milieu in women with or without hormone therapy are hypothesized to be the pathway for a number of menopause-associated modifications in physiology and disease risk. Physical activity may modify these changes in women's hormone profiles. The crucial yet complex relationship between physical activity and physiologic and pharmacologic sex hormone levels in postmenopausal women has not been investigated sufficiently. Using structured recall, physical activity was assessed longitudinally during a period of 2 years in 194 postmenopausal women (90 randomized to 1 mg 17β-estradiol treatment daily and 104 randomized to placebo) in the Estrogen in the Prevention of Atherosclerosis Trial. The levels of physical activity were correlated with the serum sex hormone and the serum hormone-binding globulin levels in each treatment group. Among the placebo-treated women, total energy expenditure was positively associated with sex hormone-binding globulin (SHBG; P < 0.001) and inversely associated with testosterones (total, bioavailable, or free) and androstenedione (P < 0.001 for all), as well as with estradiol (P = 0.02). In estradiol-treated women, estradiol levels were inversely associated with total energy expenditure (P = 0.002) and weekly hours spent in moderate or more vigorous physical activity (P = 0.001). Physical activity is associated with lower serum levels of estradiol in both hormone therapy-treated and untreated women. In placebo-treated women only, physical activity is associated with reduced androgen levels and elevated SHBG levels.

Editor's Highlight: Congener-Specific Disposition of Chiral Polychlorinated Biphenyls in Lactating Mice and Their Offspring: Implications for PCB Developmental Neurotoxicity.

PubMed

Kania-Korwel, Izabela; Lukasiewicz, Tracy; Barnhart, Christopher D; Stamou, Marianna; Chung, Haeun; Kelly, Kevin M; Bandiera, Stelvio; Lein, Pamela J; Lehmler, Hans-Joachim

2017-07-01

Chiral polychlorinated biphenyl (PCB) congeners have been implicated by laboratory and epidemiological studies in PCB developmental neurotoxicity. These congeners are metabolized by cytochrome P450 (P450) enzymes to potentially neurotoxic hydroxylated metabolites (OH-PCBs). The present study explores the enantioselective disposition and toxicity of 2 environmentally relevant, neurotoxic PCB congeners and their OH-PCB metabolites in lactating mice and their offspring following dietary exposure of the dam. Female C57BL/6N mice (8-weeks old) were fed daily, beginning 2 weeks prior to conception and continuing throughout gestation and lactation, with 3.1 µmol/kg bw/d of racemic 2,2',3,5',6-pentachlorobiphenyl (PCB 95) or 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in peanut butter; controls received vehicle (peanut oil) in peanut butter. PCB 95 levels were higher than PCB 136 levels in both dams and pups, consistent with the more rapid metabolism of PCB 136 compared with PCB 95. In pups and dams, both congeners were enriched for the enantiomer eluting second on enantioselective gas chromatography columns. OH-PCB profiles in lactating mice and their offspring were complex and varied according to congener, tissue and age. Developmental exposure to PCB 95 versus PCB 136 differentially affected the expression of P450 enzymes as well as neural plasticity (arc and ppp1r9b) and thyroid hormone-responsive genes (nrgn and mbp). The results suggest that the enantioselective metabolism of PCBs to OH-PCBs may influence neurotoxic outcomes following developmental exposures, a hypothesis that warrants further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats.

PubMed

Luine, V N

1985-08-01

Administration of estradiol to gonadectomized female, but not male rats, is associated with increased activity of choline acetyltransferase in the medial aspect of the horizontal diagonal band nucleus, the frontal cortex, and CA1 of the dorsal hippocampus. Four other basal forebrain cholinergic nuclei did not show changes in choline acetyltransferase activity after estradiol. These data have implications for possible benefits of estradiol administration to patients with senile dementia of the Alzheimer's type.

Estimation of uptake rate constants for PCB congeners accumulated by semipermeable membrane devices and brown treat (Salmo trutta)

USGS Publications Warehouse

Meadows, J.C.; Echols, K.R.; Huckins, J.N.; Borsuk, F.A.; Carline, R.F.; Tillitt, D.E.

1998-01-01

The triolein-filled semipermeable membrane device (SPMD) is a simple and effective method of assessing the presence of waterborne hydrophobic chemicals. Uptake rate constants for individual chemicals are needed to accurately relate the amounts of chemicals accumulated by the SPMD to dissolved water concentrations. Brown trout and SPMDs were exposed to PCB- contaminated groundwater in a spring for 28 days to calculate and compare uptake rates of specific PCB congeners by the two matrixes. Total PCB congener concentrations in water samples from the spring were assessed and corrected for estimated total organic carbon (TOC) sorption to estimate total dissolved concentrations. Whole and dissolved concentrations averaged 4.9 and 3.7 ??g/L, respectively, during the exposure. Total concentrations of PCBs in fish rose from 0.06 to 118.3 ??g/g during the 28-day exposure, while concentrations in the SPMD rose from 0.03 to 203.4 ??g/ g. Uptake rate constants (k1) estimated for SPMDs and brown trout were very similar, with k1 values for SPMDs ranging from one to two times those of the fish. The pattern of congener uptake by the fish and SPMDs was also similar. The rates of uptake generally increased or decreased with increasing K(ow), depending on the assumption of presence or absence of TOC.The triolein-filled semipermeable membrane device (SPMD) is a simple and effective method of assessing the presence of waterborne hydrophobic chemicals. Uptake rate constants for individual chemicals are needed to accurately relate the amounts of chemicals accumulated by the SPMB to dissolved water concentrations. Brown trout and SPMDs were exposed to PCB-contaminated groundwater in a spring for 28 days to calculate and compare uptake rates of specific PCB congeners by the two matrixes. Total PCB congener concentrations in water samples from the spring were assessed and corrected for estimated total organic carbon (TOC) sorption to estimate total dissolved concentrations. Whole and

17β-Estradiol reduces nitric oxide production in the Guinea pig cochlea.

PubMed

Heinrich, U-R; Brieger, J; Striedter, C; Fischer, I; Schmidtmann, I; Li, H; Mann, W J; Helling, K

2013-11-01

Intense noise exposure and the application of ototoxic substances result in increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO). In order to reduce the free NO concentration in the inner ear under pathological conditions, the use of natural cytoprotective substances such as 17β-estradiol is a promising therapeutic concept. In male guinea pigs the organ of Corti and the lateral wall were isolated from the cochlea and afterwards incubated for 6 h in cell-culture medium. 17β-Estradiol was adjusted in 2 concentrations to organ cultures of the right ears (12 animals per concentration). The left ears were used as controls. The NO production was quantified in the supernatant by chemiluminescence after incubation. Depending on the concentration, 17β-estradiol reduced NO in the organ of Corti by 43% (p=0.015) and 46% (p=0.026), respectively. In the lateral wall, the NO concentration was reduced by 24%, but without statistical significance (p=0.86). However, when analyzing the association between the 2 cochlear regions for each animal separately, the NO concentrations were lower in nearly all 17β-estradiol-treated ears compared to controls. In order to demonstrate the flexibility of the organ culture system, the NO donor DETA NONOate and the nitric oxide synthase inhibitors L-NAME and L-NMMA were applied. The electron microscopic analysis revealed a well-preserved cochlear cell morphology after incubation. The ability of 17β-estradiol to influence the NO production preferentially in the organ of Corti might offer new therapeutic perspectives for inner ear protection. © Georg Thieme Verlag KG Stuttgart · New York.

Changes in estradiol and testosterone levels in postmenopausal women after changes in body mass index.

PubMed

Jones, Michael E; Schoemaker, Minouk; Rae, Megan; Folkerd, Elizabeth J; Dowsett, Mitch; Ashworth, Alan; Swerdlow, Anthony J

2013-07-01

Endogenous sex hormones are risk factors for postmenopausal breast cancer. A potential route for favorable hormonal modification is weight loss. The objective of the study was to measure change in plasma estradiol and testosterone levels in postmenopausal women in relation to change in body mass index (BMI) and plasma leptin. The setting was a cohort study of over 100,000 female volunteers from the general population, United Kingdom. The participants were a sample of 177 postmenopausal women aged over 45 years who provided blood samples during 2004-2005 and again during 2010-2011. Outcomes were percentage change in plasma estradiol and testosterone levels per 1 kg/m² change in BMI and per 1 ng/mL change in plasma leptin. Among women with reduction in BMI, estradiol decreased 12.7% (95% confidence interval: [6.4%, 19.5%]; P < .0001) per kg/m² and among women with increased BMI estradiol increased 6.4% [0.2%, 12.9%] (P = .042). The corresponding figures for testosterone were 10.7% [3.0%, 19.0%] (P = .006) and 1.9% [-5.4%, 9.7%] (P = .61) per kg/m². For women with decreases and increases in leptin, estradiol decreased by 3.6% [1.3%, 6.0%] (P = .003) per ng/mL and increased by 1.7% [-0.3%, 3.6%] (P = .094), respectively. The corresponding figures for testosterone were 4.8% [2.0%, 7.8%] (P = .009) and 0.3% [-2.0%, 2.6%] (P = .82) per ng/mL. In postmenopausal women, changes in BMI and plasma leptin occurring over several years are associated with changes in estradiol and testosterone levels. The results suggest that fat loss by an individual can result in substantial decreases in postmenopausal estradiol and testosterone levels and provides support for weight management to lessen breast cancer risk.

Estradiol and Progesterone Modulate Spontaneous Sleep Patterns and Recovery from Sleep Deprivation in Ovariectomized Rats

PubMed Central

Deurveilher, Samüel; Rusak, Benjamin; Semba, Kazue

2009-01-01

Study Objectives: Women undergo hormonal changes both naturally during their lives and as a result of sex hormone treatments. The objective of this study was to gain more knowledge about how these hormones affect sleep and responses to sleep loss. Design: Rats were ovariectomized and implanted subcutaneously with Silastic capsules containing oil vehicle, 17β-estradiol and/or progesterone. After 2 weeks, sleep/wake states were recorded during a 24-h baseline period, 6 h of total sleep deprivation induced by gentle handling during the light phase, and an 18-h recovery period. Measurements and Results: At baseline and particularly in the dark phase, ovariectomized rats treated with estradiol or estradiol plus progesterone spent more time awake at the expense of non-rapid eye movement sleep (NREMS) and/or REMS, whereas those given progesterone alone spent less time in REMS than ovariectomized rats receiving no hormones. Following sleep deprivation, all rats showed rebound increases in NREMS and REMS, but the relative increase in REMS was larger in females receiving hormones, especially high estradiol. In contrast, the normal increase in NREMS EEG delta power (an index of NREMS intensity) during recovery was attenuated by all hormone treatments. Conclusions: Estradiol promotes arousal in the active phase in sleep-satiated rats, but after sleep loss, both estradiol and progesterone selectively facilitate REMS rebound while reducing NREMS intensity. These results indicate that effects of ovarian hormones on recovery sleep differ from those on spontaneous sleep. The hormonal modulation of recovery sleep architecture may affect recovery of sleep related functions after sleep loss. Citation: Deurveilher S; Rusak B; Semba K. Estradiol and progesterone modulate spontaneous sleep patterns and recovery from sleep deprivation in ovariectomized rats. SLEEP 2009;32(7):865-877. PMID:19639749

Sexual Function in Women on Estradiol or Venlafaxine for Hot Flushes: A Randomized Controlled Trial

PubMed Central

Reed, Susan D.; Mitchell, Caroline M.; Joffe, Hadine; Cohen, Lee; Shifren, Jan L.; Newton, Katherine M.; Freeman, Ellen W.; Larson, Joseph C.; Manson, JoAnn E.; LaCroix, Andrea Z.; Guthrie, Katherine A.

2014-01-01

Objective To evaluate sexual function in midlife women taking low-dose oral estradiol or venlafaxine for hot flushes. Methods In an 8-week randomized controlled trial among women aged 40-62 years, sexual function was compared between oral estradiol 0.5 mg/day or venlafaxine 75 mg/day (both compared with placebo). Measures included composite and 6 domain scores from the Female Sexual Function Index (FSFI) and sexually related personal distress. Results Participants were aged 54.6 (standard deviation [SD] 3.8) years, 59% Caucasian, with 8.1 (SD 5.3) daily hot flushes. Median composite baseline FSFI score was 16.3 (SD 11.9, n=256) for all women and 21.7 (SD 9.3, n=198) among sexually active women. Composite mean FSFI change from baseline to week-8 was 1.4 (95% Confidence Interval [CI] -0.4, 3.2) for estradiol, 1.1 (95% CI -0.5, 2.7) for venlafaxine and -0.3 (95% CI -1.6, 1.0) for placebo. Composite FSFI and sexually-related distress change from baseline did not differ between estradiol and placebo (p= 0.38, p=0.30) or venlafaxine and placebo (p=0.79, p=0.48). Among sexually active women, FSFI domain score change from baseline differences (active compared with placebo) in desire was 0.3 (95% CI 0.0, 0.6) for estradiol; -0.6 (95% CI -1.2, 0.0) in orgasm for venlafaxine, and 0.9 (95% CI 0.2, 1.6) in penetration pain for venlafaxine. No women reported adverse events related to sexual dysfunction. Conclusions Overall sexual function among nondepressed midlife women experiencing hot flushes did not change over 8-weeks with low-dose oral estradiol or venlafaxine (compared with placebo), although subtle increase in desire (estradiol), and decreases in orgasm and pain (venlafaxine) may exist. PMID:25004335

Developmental programming: contribution of prenatal androgen and estrogen to estradiol feedback systems and periovulatory hormonal dynamics in sheep.

PubMed

Veiga-Lopez, Almudena; Astapova, Olga I; Aizenberg, Esther F; Lee, James S; Padmanabhan, Vasantha

2009-04-01

Prenatal testosterone excess leads to neuroendocrine and periovulatory disruptions in the offspring culminating in progressive loss of cyclicity. It is unknown whether the mediary of these disruptions is androgen or estrogen, because testosterone can be aromatized to estrogen. Taking a reproductive life span approach of studying control, prenatal testosterone, and dihydrotestosterone-treated offspring, this study tested the hypothesis that disruptions in estradiol-negative but not -positive feedback effects are programmed by androgenic actions of testosterone and that these disruptions in turn will have an impact on the periovulatory hormonal dynamics. The approach was to test estradiol-negative and -positive feedback responses of all three groups of ovary-intact females during prepubertal age and then compare the periovulatory dynamics of luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone during the first breeding season. The findings show that estradiol-negative but not estradiol-positive feedback disruptions in prenatal testosterone-treated females are programmed by androgenic actions of prenatal testosterone excess and that follicular phase estradiol and gonadotropins surge disruptions during reproductive life are consistent with estrogenic programming. Additional studies carried out testing estradiol-positive feedback response over time found progressive deterioration of estradiol-positive feedback in prenatal testosterone-treated sheep until the time of puberty. Together, these findings provide insight into the mechanisms by which prenatal testosterone disrupts the reproductive axis. The findings may be of translational relevance since daughters of mothers with hyperandrogenism are at risk of increased exposure to androgens.

Novel chemistry of invasive plants: exotic species have more unique metabolomic profiles than native congeners.

PubMed

Macel, Mirka; de Vos, Ric C H; Jansen, Jeroen J; van der Putten, Wim H; van Dam, Nicole M

2014-07-01

It is often assumed that exotic plants can become invasive when they possess novel secondary chemistry compared with native plants in the introduced range. Using untargeted metabolomic fingerprinting, we compared a broad range of metabolites of six successful exotic plant species and their native congeners of the family Asteraceae. Our results showed that plant chemistry is highly species-specific and diverse among both exotic and native species. Nonetheless, the exotic species had on average a higher total number of metabolites and more species-unique metabolites compared with their native congeners. Herbivory led to an overall increase in metabolites in all plant species. Generalist herbivore performance was lower on most of the exotic species compared with the native species. We conclude that high chemical diversity and large phytochemical uniqueness of the exotic species could be indicative of biological invasion potential.

Estradiol and weight are covariates of paracetamol clearance in young women.

PubMed

Beleyn, B; Vermeersch, S; Kulo, A; Smits, A; Verbesselt, R; de Hoon, J N; Van Calsteren, K; Allegaert, K

2014-01-01

Paracetamol clearance differs between pregnant and non-pregnant women and between women with or without specific oral contraceptives (OCs). However, an association between female sex hormones and paracetamol clearance has never been explored. In total, 49 women at delivery, 8 female control subjects without OC use, historical data of 14 women taking OCs, and 15 postpartum observations with and without OCs were pooled to explore covariates of paracetamol clearance. All received a single intravenous 2-gram paracetamol dose, and blood samples were collected up to 6 h after dosing. High-performance liquid chromatography was used to quantify paracetamol. The area under the curve to time infinity (AUC0-∞) was determined and clearance (l/h·m(2)) was calculated by dose/ AUC0-∞. In addition, estradiol and progesterone were quantified by ELISA with electro-chemiluminescence. Median paracetamol clearance at delivery was significantly higher when compared to postpartum or non-pregnant women (11.9 vs. 6.42 and 8.4 l/h·m(2), at least p < 0.05), while an association between paracetamol clearance and estradiol was observed (R = 0.494, p < 0.0001). In non-pregnant subjects, there was no impact of OC exposure on paracetamol clearance. Multiple regression revealed a linear association (Radj = 0.41, p < 0.001) between paracetamol clearance and weight (p = 0.0462) and estradiol (p < 0.0001). Estradiol and weight in part explain the variation in paracetamol clearance in young women. © 2014 S. Karger AG, Basel.

Synchronization of follicular wave emergence in the seasonally anestrous ewe: the effects of estradiol with or without medroxyprogesterone acetate.

PubMed

Barrett, D M W; Bartlewski, P M; Duggavathi, R; Davies, K L; Huchkowsky, S L; Epp, T; Rawlings, N C

2008-04-15

Fertility is often lower in anestrous compared to cyclic ewes, after conventional estrus synchronization. We hypothesized that synchronization of ovarian follicular waves and ovulation could improve fertility at controlled breeding in anestrous ewes. Estradiol-17beta synchronizes follicular waves in cattle. The objectives of the present experiments were to study the effect of an estradiol injection, with or without a 12-d medroxyprogesterone acetate (MAP) sponge treatment, on synchronization of follicular waves and ovulation in anestrous ewes. Twenty ewes received sesame oil (n=8) or estradiol-17beta (350 microg; n=12). Eleven ewes received MAP sponges for 12d and were treated with oil (n=5) or estradiol-17beta (n=6) 6d before sponge removal. Saline (n=6) or eCG (n=6) was subsequently given to separate groups of ewes at sponge removal in the MAP/estradiol-17beta protocol. Estradiol treatment alone produced a peak in serum FSH concentrations (4.73+/-0.53 vs. 2.36+/-0.39 ng/mL for treatment vs. control; mean+/-S.E.M.) after a short-lived (6 h) suppression. Six of twelve ewes given estradiol missed a follicular wave around the time of estradiol injection. Medroxyprogesterone acetate-treated ewes given estradiol had more prolonged suppression of serum FSH concentrations (6-18 h) and a delay in the induced FSH peak (32.3+/-3.3 vs. 17.5+/-0.5 h). Wave emergence was delayed (5.7+/-0.3 vs. 1.4+/-0.7d from the time of estradiol injection), synchronized, and occurred at a predictable time (5-7 vs. 0-4d) compared to ewes given MAP alone. All ewes given eCG ovulated 3-4d after injection; this predictable time of ovulation may be efficacious for AI and embryo transfer.

Assessment of Estradiol Response after Depot Triptorelin Administration in Girls with Central Precocious Puberty.

PubMed

Freire, Analía Verónica; Gryngarten, Mirta Graciela; Ballerini, María Gabriela; Arcari, Andrea Josefina; Escobar, María Eugenia; Bergadá, Ignacio; Ropelato, María Gabriela

2016-01-01

Estradiol at baseline or after a classical gonadotropin-releasing hormone test did not reflect ovarian steroidogenesis in central precocious puberty (CPP) girls. To evaluate estradiol response to depot triptorelin, both at start and during therapy to determine how active ovarian steroidogenesis is at pubertal stage and under therapy. A prospective study was performed in 43 CPP girls. Serum luteinizing hormone and follicle-stimulating hormone at 3 h (LH-3h, FSH-3h) and estradiol at 24 h (E2-24h) after injection of depot triptorelin 3.75 mg were measured, at first dose and at 3, 6, 12, 18 and 24 months of treatment. E2-24h after depot triptorelin was >100 pg/ml after the first dose. Estradiol response (E2-24h) fell to levels <14 pg/ml in 78 out of 82 follow-up visits along 2 years of therapy. Concomitantly, LH-3h and FSH-3h were <4.0 and <6.3 IU/l, respectively. In 4 patients with inadequate treatment, E2-24h, LH-3h and FSH-3h rose to pubertal values similar to those observed at first dose. Estradiol (<14 pg/ml) assessment 24 h after depot triptorelin administration is a reliable and simple manner to confirm ovarian suppression in CPP girls during treatment. © 2015 S. Karger AG, Basel.

Estradiol worsens the syndrome of ischemia-reperfusion injury in an experimental lung transplantation model.

PubMed

Santana-Rodríguez, Norberto; Clavo, Bernardino; Llontop, Pedro; López, Ana; García-Castellano, José Manuel; Machín, Rubén P; Ponce, Miguel A; Fiuza, María D; García-Herrera, Ricardo; Brito, Yanira; Yordi, Nagib Atallah; Chirino, Ricardo

2011-06-01

Ischemia-reperfusion injury (IRI) is a common complication after lung transplantation. There is evidence that reactive oxygen species are involved in its pathogenesis. We designed an experimental study to evaluate whether the administration of antioxidants to lung transplantation recipients protects against IRI and early acute rejection (AR). Twenty-five rats received left lung transplants after 6 h of ischemia. Fifty minutes before the reperfusion, groups of five rats received a single dose of desferrioxamine (20 mg/kg), estradiol (25 mg/kg), or melatonin (10 mg/kg). The animals were killed 48 h after surgery and the postoperative outcome, IRI, and AR were evaluated. The frequency of severe injury and of moderate-to-severe edema was higher in animals treated with estradiol than in the control group (P = 0.022 and P = 0.026, respectively). No significant changes in the degree of IRI or AR were observed in the groups treated with desferrioxamine or melatonin. In our study, treatment with the antioxidants melatonin or desferrioxamine before reperfusion had no effects on IRI damage or on AR frequency or severity. However, treatment with estradiol resulted in a worse postoperative outcome and in severe edema. Therefore, despite the antioxidant capacity of estradiol, it is recommended that an evaluation of these adverse effects of estradiol in human lung transplant recipients be performed.

Arsenic and 17-β-estradiol bind to each other and neutralize each other’s signaling effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Sukhdeep; Mukherjee, Tapan K.; Guptasarma, Purnananda, E-mail: guptasarma@iisermohali.ac.in

We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other’s independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spectroscopy, chromatography-coupled voltammometry and 1-D {sup 1}H and {sup 13}C NMR spectroscopy. Binding leads to attenuation of E2’s hydroxyl {sup 1}H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other’s levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in agemore » of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas. - Highlights: • Difference absorption spectroscopy suggests that arsenic binds to estradiol. • Interaction with arsenic alters {sup 1}H and {sup 13}C NMR spectra of estradiol at positions C3 and C17. • Estradiol traps arsenic on C{sub 18} reverse-phase columns. • Estradiol and arsenic neutralize each other’s ability to stimulate scratch wound healing. • Arsenic appears to form pnictogen bonds with hydroxyls on estradiol.« less

Lack of effects of a "sobering" product, "Eezup!", on the blood ethanol and congener alcohol concentration.

PubMed

Wunder, Cora; Hain, Sarah; Koelzer, Sarah C; Paulke, Alexander; Verhoff, Marcel A; Toennes, Stefan W

2017-09-01

The lifestyle product 'Eezup!' appeared on the German market and promised to normalize energy metabolism. Among vitamins (B 1 , B 2 , B 6 , C, E and zinc), rice protein and fructose the addition of alcohol dehydrogenase and catalase enzymes is a novel approach. The product was advertised as capable of boosting the rate of alcohol elimination. Seventeen subjects (11 men, 6 women, 19-58 years old), participated in a two-way crossover drinking study. Unfiltered wheat beer (4.4g% alcohol content) was drank within one hour to reach blood alcohol concentrations of 1‰ (1g/kg whole blood). On one day "Eezup!" was taken according to the manufacturer's instructions before and after drinking which was substituted for a placebo on the second test day. Blood samples were taken during 9h and ethanol and congener alcohols were determined. A comparison of C max , t max , area under the curve (AUC) for ethanol and congener alcohols, and the hourly elimination rate of ethanol (β 60 ) was performed to investigate an effect of Eezup!. Ethanol concentrations (Cmax) were in the range of 0,63-1,00‰ (median 0,85‰) and 0.62-1.22‰ (median 0.84‰) in the placebo and "Eezup!" condition, respectively, and not statistically different. Also t max (1-2.5h) and AUCs did not differ. The ethanol elimination rates were 0.16‰/h (0.14-0.19‰/h) and 0.17‰/h (0.14-0.22 ‰/h) in the placebo and "Eezup!" condition without significant difference. The pharmacokinetic parameters of the congener alcohols (1-propanol, isobutanol, 3-methyl-1-butanol, 2-methyl-1-butanol) as well as of methanol did also not differ. The results of the present study failed to show any effect of the sobering product "Eezup!" on the amount of ethanol and congener alcohols absorbed (C max , t max, AUC) and on the ethanol elimination rate (β 60 ). Copyright © 2017 Elsevier B.V. All rights reserved.

Development and validation of in vitro-in vivo correlation (IVIVC) for estradiol transdermal drug delivery systems.

PubMed

Yang, Yang; Manda, Prashanth; Pavurala, Naresh; Khan, Mansoor A; Krishnaiah, Yellela S R

2015-07-28

The objective of this study was to develop a level A in vitro-in vivo correlation (IVIVC) for drug-in-adhesive (DIA) type estradiol transdermal drug delivery systems (TDDS). In vitro drug permeation studies across human skin were carried out to obtain the percent of estradiol permeation from marketed products. The in vivo time versus plasma concentration data of three estradiol TDDS at drug loadings of 2.0, 3.8 and 7.6mg (delivery rates of 25, 50 and 100μg/day, respectively) was deconvoluted using Wagner-Nelson method to obtain percent of in vivo drug absorption in postmenopausal women. The IVIVC between the in vitro percent of drug permeation (X) and in vivo percent of drug absorption (Y) for these three estradiol TDDS was constructed using GastroPlus® software. There was a high correlation (R(2)=1.0) with a polynomial regression of Y=-0.227X(2)+0.331X-0.001. These three estradiol TDDS were used for internal validation whereas another two products of the same formulation design (with delivery rates of 60 and 100μg/day) were used for external validation. The predicted estradiol serum concentrations (convoluted from in vitro skin permeation data) were compared with the observed serum concentrations for the respective products. The developed IVIVC model passed both the internal and external validations as the prediction errors (%PE) for Cmax and AUC were less than 15%. When another marketed estradiol TDDS with a delivery rate of 100μg/day but with a slight variation in formulation design was chosen, it did not pass external validation indicating the product-specific nature of IVIVC model. Results suggest that the IVIVC model developed in this study can be used to successfully predict the in vivo performance of the same estradiol TDDS with in vivo delivery rates ranging from 25 to 100μg/day. Published by Elsevier B.V.

Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns ▿

PubMed Central

Giannoni, Eric; Guignard, Laurence; Knaup Reymond, Marlies; Perreau, Matthieu; Roth-Kleiner, Matthias; Calandra, Thierry; Roger, Thierry

2011-01-01

Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period. PMID:21518785

Decrease in water-soluble 17beta-Estradiol and testosterone in composted poultry manure with time.

PubMed

Hakk, Heldur; Millner, Patricia; Larsen, Gerald

2005-01-01

Little attention has been paid to the environmental fate of the hormones 17beta-estradiol and testosterone excreted in animal waste. Land application of manure has a considerable potential to affect the environment with these endocrine disrupting compounds (EDCs). Composting is known to decompose organic matter to a stable, humus-like material. The goal of the present study was to quantitatively assess levels of water-soluble 17beta-estradiol and testosterone in composting chicken manure with time. Chicken layer manure was mixed with hay, straw, decomposed leaves, and starter compost, adjusted to approximately 60% moisture, and placed into a windrow. A clay-amended windrow was also prepared. Windrows were turned weekly, and temperature, oxygen, and CO(2) in the composting mass were monitored for either 133 or 139 d. Commercial enzyme immunoassay kits were used to quantitate the levels of 17beta-estradiol and testosterone in aqueous sample extracts. Water-soluble quantities of both hormones diminished during composting. The decrease in 17beta-estradiol followed first-order kinetics, with a rate constant k = -0.010/d. Testosterone levels declined at a slightly higher rate than 17beta-estradiol (i.e., k = -0.015/d). Both hormones could still be measured in aqueous extracts of compost sampled at the conclusion of composting. The decline in water-soluble 17beta-estradiol and testosterone in extracts of clay-amended compost was not statistically different from normal compost. These data suggest that composting may be an environmentally friendly technology suitable for reducing, but not eliminating, the concentrations of these endocrine disrupting hormones at concentrated animal operation facilities.

Estradiol Variability, Stressful Life Events and the Emergence of Depressive Symptomatology during the Menopause Transition

PubMed Central

Gordon, Jennifer L.; Rubinow, David R.; Eisenlohr-Moul, Tory A; Leserman, Jane; Girdler, Susan S.

2015-01-01

Objective To examine the role of estradiol fluctuation in triggering depressive symptoms in the menopause transition and assess the role of recent very stressful life events (VSLEs) as a moderating factor in this relationship. Methods 52 euthymic women in the menopause transition or early postmenopause (age 45–60) who were assigned to the placebo arm of a randomized controlled trial of hormone therapy provided the data for this report. At enrollment, women’s experience of recent VSLEs, depressive symptoms, serum estradiol and progesterone were assessed. At months 1, 8 and 14, depressive symptoms and hormones were re-assessed and participants underwent a stressor battery involving a speech and a mental arithmetic task. Participants rated their feelings of anxiety, fear, anger and rejection. The standard deviation of estradiol provided an index of hormone variability over the entire 14 months. Results Greater estradiol variability across the 14 months predicted greater depressive symptoms at month 14, though only in women reporting a higher number of VSLEs at baseline (39% of women reported ≤1 recent event). Greater estradiol variability also predicted greater feelings of rejection to the laboratory stressor at months 8 and 14. Furthermore, among women reporting higher VSLEs at baseline, feelings of rejection in response to the laboratory stressor at month 8 predicted depressive symptoms at month 14. Conclusion These data suggest estradiol variability may enhance emotional sensitivity to psychosocial stress, particularly sensitivity to social rejection. Combined with VSLEs proximate to the menopause transition, this increased sensitivity may contribute to the development of depressed mood. PMID:26529616

In vitro bioactivity of 17alpha-estradiol.

PubMed

Sievernich, André; Wildt, Ludwig; Lichtenberg-Fraté, Hella

2004-12-01

A miniaturised short-term in vitro assay based on the activation of the human estrogen receptor alpha and genetically modified yeast (Saccharomyces cerevisiae) cells was performed to explore the capacity of this system to monitor the bioactivity of estrogenic compounds, particularly 17alpha- and 17beta-estradiol. Together with the human estrogen receptor (hER)-alpha plasmid, the reporter plasmid containing a yeast-optimised version of the green fluorescent protein (yEGFP) linked to three repeats of the cis-acting estrogen hormone-responsive element (ERE) were expressed in a strain being deleted in the pleiotropic drug resistance transporters Pdr5, Snq2 and Yor1, known to facilitate efflux of organic compounds including steroids and chemotherapeutics. Agonists that bind to hER in vitro trigger estrogen receptor-mediated transcriptional activation of the GFP reporter gene monitored by fluorescence emission at 535 nm. The sensitivity of the assay was tested with various 17alpha- and 17beta-estradiol concentrations, yielding a detection limit of 5 pg/ml (0.018 nM) for the agonist 17beta-E2 in solvent and in human charcoal-stripped serum using a S. cerevisiae pdr5, snq2 and yor1 mutant strain. For 17alpha-estradiol only, at approximately 1500 pg/ml a similar fluorescence response compared to 100 pg/ml 17beta-E2 was observed implicating a much weaker potency of this stereoisomer. The specificity of the system was tested by expression of a truncated hER lacking the ligand-binding domain E and by administration of the androgen, 4-androsten 3,17 dione. Both controls did not yield an increase in fluorescence emission. This fluorescence emission assay enables detection of estrogenic biological activity induced by direct agonists, such as 17beta-E2 at concentrations similar to those found in human sera or by estrogen-like chemicals.

Why use of dienogest for the first contraceptive pill with estradiol?

PubMed

Mueck, Alfred O; Seeger, Harald; Bühling, Kai J

2010-02-01

Dienogest (DNG) has the essential properties of an effective progestogen for use in a new contraceptive pill using estradiol valerate as estrogenic component -- it inhibits ovulation and protects against endometrial proliferation. DNG is a derivative of norethisterone (NET), but has a cyanomethyl- instead of an ethinyl-group in C17 position which may offer a variety of benefits regarding hepatic effects. The similarity to NET is reflected in the high endometriotropy and in similar pharmacokinetics like short plasma half-live and high bioavailability. However, DNG also elicits properties of progesterone derivatives like neutrality in metabolic and cardiovascular system and considerable antiandrogenic activity, the latter increased by lack of binding to SHBG as specific property of DNG. It has no glucocorticoid and antimineralocorticoid activity and has no antiestrogenic activity with the consequence that possible beneficial estradiol effects should not be antagonized. This may be of special importance for the tolerability and safety of the first pill with estradiol valerate instead of ethinylestradiol, although well-designed postmarketing studies are still ongoing to demonstrate what can be expected on the basis of pharmacology.

Developmental Programming: Contribution of Prenatal Androgen and Estrogen to Estradiol Feedback Systems and Periovulatory Hormonal Dynamics in Sheep1

PubMed Central

Veiga-Lopez, Almudena; Astapova, Olga I.; Aizenberg, Esther F.; Lee, James S.; Padmanabhan, Vasantha

2009-01-01

Prenatal testosterone excess leads to neuroendocrine and periovulatory disruptions in the offspring culminating in progressive loss of cyclicity. It is unknown whether the mediary of these disruptions is androgen or estrogen, because testosterone can be aromatized to estrogen. Taking a reproductive life span approach of studying control, prenatal testosterone, and dihydrotestosterone-treated offspring, this study tested the hypothesis that disruptions in estradiol-negative but not -positive feedback effects are programmed by androgenic actions of testosterone and that these disruptions in turn will have an impact on the periovulatory hormonal dynamics. The approach was to test estradiol-negative and -positive feedback responses of all three groups of ovary-intact females during prepubertal age and then compare the periovulatory dynamics of luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone during the first breeding season. The findings show that estradiol-negative but not estradiol-positive feedback disruptions in prenatal testosterone-treated females are programmed by androgenic actions of prenatal testosterone excess and that follicular phase estradiol and gonadotropins surge disruptions during reproductive life are consistent with estrogenic programming. Additional studies carried out testing estradiol-positive feedback response over time found progressive deterioration of estradiol-positive feedback in prenatal testosterone-treated sheep until the time of puberty. Together, these findings provide insight into the mechanisms by which prenatal testosterone disrupts the reproductive axis. The findings may be of translational relevance since daughters of mothers with hyperandrogenism are at risk of increased exposure to androgens. PMID:19122183

Fate of glucuronide conjugated estradiol in the environment

USDA-ARS?s Scientific Manuscript database

The fate and transport of conjugated reproductive hormones, which are polar compared to parent hormones, are little understood. Laboratory bench-scale soil (Hamar; Sandy, mixed, frigid typic Endoaquolls) sorption studies were conducted using [14C] 17ß-estradiol-3-glucuronide for a range of concentra...

Coexposure of dioxin-like polychlorinated biphenyls and polychlorinated dibenzo-p-dioxins and dibenzofurans in free-range hens and implications derived from congener profile analysis.

PubMed

Lin, Chingju; Hsu, Jing-Fang; Liao, Pao-Chi

2012-02-29

The consumption of free-range eggs is becoming more popular worldwide. We analyzed the levels of 12 dioxin-like polychlorinated biphenyls (dl-PCBs) and their congener profiles from 6 free-range and 12 caged egg samples. The mean levels of dl-PCBs in the free-range samples were 5.4 times higher than those in caged eggs. All egg samples exhibited at least two characteristic dl-PCB congener patterns, which reflected distinctive contamination sources. Additionally, for the first time, we demonstrated that the dl-PCB levels in the free-range eggs were highly correlated with elevated levels of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) (r = 0.986; p < 0.001), indicating a coexposure scenario in free-range hens. Cluster analysis of congener patterns implied that this coexposure scenario could be attributed to distinct dl-PCB and PCDD/F sources. This congener profile information provides insights from a different perspective for further identifying potential dl-PCB and PCDD/F sources in the polluted free-range eggs.

Systemic functional expression of N-acetyltransferase polymorphism in the F344 Nat2 congenic rat

PubMed Central

Hein, David W.; Bendaly, Jean; Neale, Jason R.; Doll, Mark A.

2008-01-01

Rat lines congenic for the rat N-acetyltransferase 2 [(RAT)Nat2] gene were constructed and characterized. F344 (homozygous Nat2 rapid) males were mated to WKY (homozygous Nat2 slow) females to produce heterozygous F1. F1 females were then backcrossed to F344 males. Heterozygous acetylator female progeny from this and each successive backcross were identified by rat Nat2 genotyping and mated with F344 rapid acetylator males. Following ten generations of backcross mating, heterozygous acetylator brother/sister progeny were mated to produce the homozgygous rapid and slow acetylator Nat2 congenic rat lines. p-Aminobenzoic acid (selective for rat NAT2) and 4-aminobiphenyl N-acetyltransferase activities were expressed in all tissues examined (liver, lung, esophagus, stomach, small intestine, colon, pancreas, kidney, skin, leukocytes, and urinary bladder in male and female rats and in breast of female and prostate of male rats). NAT2 expression in rat extrahepatic tissues was much higher than in liver. In each tissue, activities were Nat2-genotype dependent, with highest levels in homozygous rapid acetylators, intermediate levels in heterozygous acetylators, and lowest in homozygous slow acetylators. Sulfamethazine (selective for rat NAT1) N-acetyltransferase activities were observed in all tissues examined in both male and female rats except for breast (females), bladder and leukocytes. In each tissue, the activity was Nat2-genotype independent, with similar levels in homozygous rapid, heterozygous, and homozygous slow acetylators. These congenic rat lines are useful to investigate the role of NAT2 genetic polymorphism in susceptibility to cancers related to arylamine carcinogen exposures. PMID:18799801

Effects of estradiol and venlafaxine on insomnia symptoms and sleep quality in women with hot flashes.

PubMed

Ensrud, Kristine E; Guthrie, Katherine A; Hohensee, Chancellor; Caan, Bette; Carpenter, Janet S; Freeman, Ellen W; LaCroix, Andrea Z; Landis, Carol A; Manson, JoAnn; Newton, Katherine M; Otte, Julie; Reed, Susan D; Shifren, Jan L; Sternfeld, Barbara; Woods, Nancy F; Joffe, Hadine

2015-01-01

Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes. 3-arm double-blind randomized trial. Participants assigned in a 2:2:3 ratio to 17β estradiol 0.5 mg/day (n = 97), venlafaxine XR 75 mg/day (n = 96), or placebo (n = 146) for 8 weeks. Academic research centers. 339 community-dwelling perimenopausal and postmenopausal women with ≥2 bothersome hot flashes per day. Insomnia symptoms (Insomnia Severity Index [ISI]) and sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at baseline, week 4 and 8; 325 women (96%) provided ISI data and 312 women (92%) provided PSQI data at baseline and follow-up. At baseline, mean (SD) hot flash frequency was 8.1/day (5.3), mean ISI was 11.1 (6.0), and mean PSQI was 7.5 (3.4). Mean (95% CI) change from baseline in ISI at week 8 was -4.1 points (-5.3 to -3.0) with estradiol, -5.0 points (-6.1 to -3.9) with venlafaxine, and -3.0 points (-3.8 to -2.3) with placebo (P overall treatment effect vs. placebo 0.09 for estradiol and 0.007 for venlafaxine). Mean (95% CI) change from baseline in PSQI at week 8 was -2.2 points (-2.8 to -1.6) with estradiol, -2.3 points (-2.9 to -1.6) with venlafaxine, and -1.2 points (-1.7 to -0.8) with placebo (P overall treatment effect vs. placebo 0.04 for estradiol and 0.06 for venlafaxine). Among perimenopausal and postmenopausal women with hot flashes, both low dose oral estradiol and low-dose venlafaxine compared with placebo modestly reduced insomnia symptoms and improved subjective sleep quality. NCT01418209 at www.clinicaltrials.gov. © 2014 Associated Professional Sleep Societies, LLC.

G protein-coupled receptor 30 localizes to the endoplasmic reticulum and is not activated by estradiol.

PubMed

Otto, Christiane; Rohde-Schulz, Beate; Schwarz, Gilda; Fuchs, Iris; Klewer, Mario; Brittain, Dominic; Langer, Gernot; Bader, Benjamin; Prelle, Katja; Nubbemeyer, Reinhard; Fritzemeier, Karl-Heinrich

2008-10-01

The classical estrogen receptor (ER) mediates genomic as well as rapid nongenomic estradiol responses. In case of genomic responses, the ER acts as a ligand-dependent transcription factor that regulates gene expression in estrogen target tissues. In contrast, nongenomic effects are initiated at the plasma membrane and lead to rapid activation of cytoplasmic signal transduction pathways. Recently, an orphan G protein-coupled receptor, GPR30, has been claimed to bind to and to signal in response to estradiol. GPR30 therefore might mediate some of the nongenomic estradiol effects. The present study was performed to clarify the controversy about the subcellular localization of GPR30 and to gain insight into the in vivo function of this receptor. In transiently transfected cells as well as cells endogenously expressing GPR30, we confirmed that the receptor localized to the endoplasmic reticulum. However, using radioactive estradiol, we observed only saturable, specific binding to the classical ER but not to GPR30. Estradiol stimulation of cells expressing GPR30 had no impact on intracellular cAMP or calcium levels. To elucidate the physiological role of GPR30, we performed in vivo experiments with estradiol and G1, a compound that has been claimed to act as selective GPR30 agonist. In two classical estrogen target organs, the uterus and the mammary gland, G1 did not show any estrogenic effect. Taken together, we draw the conclusion that GPR30 is still an orphan receptor.

Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

PubMed Central

Scholz, Paul; Mohrhardt, Julia; Gisselmann, Günter; Hatt, Hanns

2016-01-01

The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30. PMID:27494699

Fractionation and current time trends of PCB congeners: evolvement of distributions 1950-2010 studied using a global atmosphere-ocean general circulation model

NASA Astrophysics Data System (ADS)

Lammel, G.; Stemmler, I.

2012-05-01

PCBs are ubiquitous environmental pollutants expected to decline in abiotic environmental media in response to decreasing primary emissions since the 1970s. A coupled atmosphere-ocean general circulation model with embedded dynamic sub-models for atmospheric aerosols and the marine biogeochemistry and air-surface exchange processes with soils, vegetation and the cryosphere is used to study the transport and fate of four PCB congeners covering a range of 3-7 chlorine atoms. The change of the geographic distribution of the PCB mixture reflects the sources and sinks' evolvement over time. Globally, secondary emissions (re-volatilisation from surfaces) are on the long term increasingly gaining importance over primary emissions. They are most important for congeners of medium hydrophobicity (5-6 chlorine atoms). Their levels are predicted to decrease slowest. Congeners' fractionation is characterized both geographically and temporally. It causes enrichment of the lighter, less persistent congeners and more delayed decreasing levels in high latitudes in response to decreasing emissions. Delivery of contaminants to high latitudes is predicted to be more efficient than previously suggested. The results suggest furthermore that the effectiveness of emission control measures may significantly vary among substances: trends of decline in abiotic environmental media do not only vary with latitude (slow in high latitudes), but do also show longitudinal gradients

Dietary Isoflavone-Dependent and Estradiol Replacement Effects on Body Weight in the Ovariectomized (OVX) Rat.

PubMed

Russell, Ashley L; Grimes, Jamie Moran; Cruthirds, Danette F; Westerfield, Joanna; Wooten, Lawren; Keil, Margaret; Weiser, Michael J; Landauer, Michael R; Handa, Robert J; Wu, T John; Larco, Darwin O

2017-06-01

17β-Estradiol is known to regulate energy metabolism and body weight. Ovariectomy results in body weight gain while estradiol administration results in a reversal of weight gain. Isoflavones, found in rodent chow, can mimic estrogenic effects making it crucial to understand the role of these compounds on metabolic regulation. The goal of this study is to examine the effect of dietary isoflavones on body weight regulation in the ovariectomized rat. This study will examine how dietary isoflavones can interact with estradiol treatment to affect body weight. Consistent with previous findings, animals fed an isoflavone-rich diet had decreased body weight (p<0.05), abdominal fat (p<0.05), and serum leptin levels (p<0.05) compared to animals fed an isoflavone-free diet. Estradiol replacement resulted in decreased body weight (p<0.05), abdominal fat (p<0.05), and serum leptin (p<0.05). Current literature suggests the involvement of cytokines in the inflammatory response of body weight gain. We screened a host of cytokines and chemokines that may be altered by dietary isoflavones or estradiol replacement. Serum cytokine analysis revealed significant (p<0.05) diet-dependent increases in inflammatory cytokines (keratinocyte-derived chemokine). The isoflavone-free diet in OVX rats resulted in the regulation of the following cytokines and chemokines: interleukin-10, interleukin-18, serum regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 (p<0.05). Overall, these results reveal that estradiol treatment can have differential effects on energy metabolism and body weight regulation depending on the presence of isoflavones in rodent chow. © Georg Thieme Verlag KG Stuttgart · New York.

Estradiol promotes pentose phosphate pathway addiction and cell survival via reactivation of Akt in mTORC1 hyperactive cells.

PubMed

Sun, Y; Gu, X; Zhang, E; Park, M-A; Pereira, A M; Wang, S; Morrison, T; Li, C; Blenis, J; Gerbaudo, V H; Henske, E P; Yu, J J

2014-05-15

Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease that can lead to respiratory failure. LAM cells typically have inactivating TSC2 mutations, leading to mTORC1 activation. The gender specificity of LAM suggests that estradiol contributes to disease development, yet the underlying pathogenic mechanisms are not completely understood. Using metabolomic profiling, we identified an estradiol-enhanced pentose phosphate pathway signature in Tsc2-deficient cells. Estradiol increased levels of cellular NADPH, decreased levels of reactive oxygen species, and enhanced cell survival under oxidative stress. Mechanistically, estradiol reactivated Akt in TSC2-deficient cells in vitro and in vivo, induced membrane translocation of glucose transporters (GLUT1 or GLUT4), and increased glucose uptake in an Akt-dependent manner. (18)F-FDG-PET imaging demonstrated enhanced glucose uptake in xenograft tumors of Tsc2-deficient cells from estradiol-treated mice. Expression array study identified estradiol-enhanced transcript levels of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway. Consistent with this, G6PD was abundant in xenograft tumors and lung metastatic lesions of Tsc2-deficient cells from estradiol-treated mice. Molecular depletion of G6PD attenuated estradiol-enhanced survival in vitro, and treatment with 6-aminonicotinamide, a competitive inhibitor of G6PD, reduced lung colonization of Tsc2-deficient cells. Collectively, these data indicate that estradiol promotes glucose metabolism in mTORC1 hyperactive cells through the pentose phosphate pathway via Akt reactivation and G6PD upregulation, thereby enhancing cell survival under oxidative stress. Interestingly, a strong correlation between estrogen exposure and G6PD was also found in breast cancer cells. Targeting the pentose phosphate pathway may have therapeutic benefit for LAM and possibly other hormonally dependent neoplasms.

Estradiol promotes pentose phosphate pathway addiction and cell survival via reactivation of Akt in mTORC1 hyperactive cells

PubMed Central

Sun, Y; Gu, X; Zhang, E; Park, M-A; Pereira, A M; Wang, S; Morrison, T; Li, C; Blenis, J; Gerbaudo, V H; Henske, E P; Yu, J J

2014-01-01

Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease that can lead to respiratory failure. LAM cells typically have inactivating TSC2 mutations, leading to mTORC1 activation. The gender specificity of LAM suggests that estradiol contributes to disease development, yet the underlying pathogenic mechanisms are not completely understood. Using metabolomic profiling, we identified an estradiol-enhanced pentose phosphate pathway signature in Tsc2-deficient cells. Estradiol increased levels of cellular NADPH, decreased levels of reactive oxygen species, and enhanced cell survival under oxidative stress. Mechanistically, estradiol reactivated Akt in TSC2-deficient cells in vitro and in vivo, induced membrane translocation of glucose transporters (GLUT1 or GLUT4), and increased glucose uptake in an Akt-dependent manner. 18F-FDG-PET imaging demonstrated enhanced glucose uptake in xenograft tumors of Tsc2-deficient cells from estradiol-treated mice. Expression array study identified estradiol-enhanced transcript levels of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway. Consistent with this, G6PD was abundant in xenograft tumors and lung metastatic lesions of Tsc2-deficient cells from estradiol-treated mice. Molecular depletion of G6PD attenuated estradiol-enhanced survival in vitro, and treatment with 6-aminonicotinamide, a competitive inhibitor of G6PD, reduced lung colonization of Tsc2-deficient cells. Collectively, these data indicate that estradiol promotes glucose metabolism in mTORC1 hyperactive cells through the pentose phosphate pathway via Akt reactivation and G6PD upregulation, thereby enhancing cell survival under oxidative stress. Interestingly, a strong correlation between estrogen exposure and G6PD was also found in breast cancer cells. Targeting the pentose phosphate pathway may have therapeutic benefit for LAM and possibly other hormonally dependent neoplasms. PMID:24832603

A Congenic Line of the C57BL/6J Mouse Strain that is Proficient in Melatonin Synthesis.

PubMed

Zhang, Zhijing; Silveyra, Eduardo; Jin, Nange; Ribelayga, Christophe P

2018-05-16

The C57BL/6J (B6) is the most common inbred mouse strain used in biomedical research in the United States. Yet, this strain is notoriously known for being deficient in the biosynthesis of melatonin, an important effector of circadian clocks in the brain and in the retina. Melatonin deficiency in this strain results from non-functional alleles of the genes coding two key enzymes of the melatonin synthesis pathway: arylalkylamine-N-acetyltransferase (Aanat) and N-acetylserotonin-O-methyltransferase (Asmt). By introducing functional alleles of the Aanat and Asmt genes from the melatonin-proficient CBA/CaJ (CBA) mouse strain to B6, we have generated a B6 congenic line that has acquired the capacity of rhythmic melatonin synthesis. In addition, the melatonin-dependent rhythm of dopamine release in the retina is restored in the B6 congenic line. Finally, we have partially characterized the Aanat and Asmt genes of the CBA strain and have identified multiple differences between CBA and B6 alleles, including single nucleotide polymorphism and deletion/insertion of DNA segments of various sizes. As an improved model organism with functional components of the melatonin synthesis pathway and melatonin-dependent circadian regulations, the new line will be useful to researchers studying melatonin physiological functions in a variety of fields including, but not limited to, circadian biology and neuroscience. In particular, the congenic line will be useful to speed up introduction of melatonin production capacity into genetically-modified mouse lines of interest such as knockout lines, many of which are on B6 or mixed B6 backgrounds. The melatonin-proficient B6 congenic line will be widely distributed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Laboratory estimation of net trophic transfer efficiencies of PCB congeners to lake trout (Salvelinus namaycush) from its prey

USGS Publications Warehouse

Madenjian, Charles P.; Rediske, Richard R.; O'Keefe, James P.; David, Solomon R.

2014-01-01

A technique for laboratory estimation of net trophic transfer efficiency (γ) of polychlorinated biphenyl (PCB) congeners to piscivorous fish from their prey is described herein. During a 135-day laboratory experiment, we fed bloater (Coregonus hoyi) that had been caught in Lake Michigan to lake trout (Salvelinus namaycush) kept in eight laboratory tanks. Bloater is a natural prey for lake trout. In four of the tanks, a relatively high flow rate was used to ensure relatively high activity by the lake trout, whereas a low flow rate was used in the other four tanks, allowing for low lake trout activity. On a tank-by-tank basis, the amount of food eaten by the lake trout on each day of the experiment was recorded. Each lake trout was weighed at the start and end of the experiment. Four to nine lake trout from each of the eight tanks were sacrificed at the start of the experiment, and all 10 lake trout remaining in each of the tanks were euthanized at the end of the experiment. We determined concentrations of 75 PCB congeners in the lake trout at the start of the experiment, in the lake trout at the end of the experiment, and in bloaters fed to the lake trout during the experiment. Based on these measurements, γ was calculated for each of 75 PCB congeners in each of the eight tanks. Mean γ was calculated for each of the 75 PCB congeners for both active and inactive lake trout. Because the experiment was replicated in eight tanks, the standard error about mean γ could be estimated. Results from this type of experiment are useful in risk assessment models to predict future risk to humans and wildlife eating contaminated fish under various scenarios of environmental contamination.

Development of molecularly imprinted column-on line-two dimensional liquid chromatography for rapidly and selectively monitoring estradiol in cosmetics.

PubMed

Guo, Pengqi; Xu, Xinya; Xian, Liang; Ge, Yanhui; Luo, Zhimin; Du, Wei; Jing, Wanghui; Zeng, Aiguo; Chang, Chun; Fu, Qiang

2016-12-01

Nowadays, the illegal use of estradiol in cosmetics has caused a series of events which endangering public health seriously. Therefore, it is imperative to establish a simple, fast and specific method for monitoring the illegal use of estradiol in cosmetics. In current study, we developed a molecular imprinted monolithic column two dimensional liquid chromatography method (MIMC-2D-LC) for rapid and selective determination of estradiol in various cosmetic samples. The best polymerization, morphology, structure property, surface groups, and the adsorption performance of the prepared material were investigated. The MIMC-2D-LC was validated and successfully used for detecting estradiol in cosmetic samples with good selectivity, sensitivity, efficiency and reproducibility. The linear range of the MIMC-2D-LC for estradiol was 0.5-50μgg -1 with the limit of detection of 0.08μgg -1 . Finally, six batches of cosmetic samples obtained from local markets were tested by the proposed method. The test results showed that the illegal use of estradiol still existed in the commercially available samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases.

PubMed

Obradovic, Milan; Bjelogrlic, Predrag; Rizzo, Manfredi; Katsiki, Niki; Haidara, Mohamed; Stewart, Alan J; Jovanovic, Aleksandra; Isenovic, Esma R

2013-09-01

Obesity is associated with aberrant sodium/potassium-ATPase (Na(+)/K(+)-ATPase) activity, apparently linked to hyperglycemic hyperinsulinemia, which may repress or inactivate the enzyme. The reduction of Na(+)/K(+)-ATPase activity in cardiac tissue induces myocyte death and cardiac dysfunction, leading to the development of myocardial dilation in animal models; this has also been documented in patients with heart failure (HF). During several pathological situations (cardiac insufficiency and HF) and in experimental models (obesity), the heart becomes more sensitive to the effect of cardiac glycosides, due to a decrease in Na(+)/K(+)-ATPase levels. The primary female sex steroid estradiol has long been recognized to be important in a wide variety of physiological processes. Numerous studies, including ours, have shown that estradiol is one of the major factors controlling the activity and expression of Na(+)/K(+)-ATPase in the cardiovascular (CV) system. However, the effects of estradiol on Na(+)/K(+)-ATPase in both normal and pathological conditions, such as obesity, remain unclear. Increasing our understanding of the molecular mechanisms by which estradiol mediates its effects on Na(+)/K(+)-ATPase function may help to develop new strategies for the treatment of CV diseases. Herein, we discuss the latest data from animal and clinical studies that have examined how pathophysiological conditions such as obesity and the action of estradiol regulate Na(+)/K(+)-ATPase activity.

Polybrominated diphenyl ether congeners in the young-of-the-year bluefish, Pomatomus saltatrix, from several nursery habitats along the US Atlantic coastline.

PubMed

Deshpande, Ashok D; Dockum, Bruce W

2013-12-15

Spatial trends of polybrominated diphenyl ether (PBDE) congeners were examined by using high resolution gas chromatography-low resolution electron impact mass spectrometry (GC-EIMS) in 414 samples of young-of-the-year (YOY) bluefish (Pomatomus saltatrix) collected from a total of 29 nursery habitats along the US Atlantic coastline from Massachusetts to Florida. Of the 26 target PBDE congeners, BDE-47 (4 Br), BDE-100 (5 Br), BDE-49 (4 Br), BDE-99 (5 Br), and BDE-154 (6 Br) were the five most frequently detected congeners in the order of decreasing importance. The sum of the concentrations of five major PBDE congeners, referred to as ΣPBDEs, varied between estuaries and also among samples from a given estuary. ΣPBDEs were lowest in YOY bluefish from Vineyard Sound, Nantucket Sound, Great Bay, Delaware Bay, Lynnhaven Bay, Cape Lookout, and Crescent Beach, with maximum ΣPBDE concentrations below 10 ng/g wet weight. ΣPBDEs in three bluefish samples from Stamford Harbor were detected at relatively high to unusually high concentrations of 69.1, 205, and 561 ng/g wet weight. ΣPBDE values for other Stamford Harbor bluefish were generally low. Highest PBDE concentrations were detected in the vicinity of industrial and urban locations within the New York-New Jersey metropolitan complex. Among them, bluefish from Newark Bay were generally the most contaminated with an average ΣPBDE value of 56.6 ± 30.8 ng/g wet weight. ΣPBDEs in bluefish from Newark Bay were numerically greater than ΣPBDEs in bluefish from all locations, however these differences were not statistically significant. Modest to good correlations between ΣPBDEs and lipids were observed for YOY bluefish from Buzzards Bay, Upper New Bedford Harbor, Lower New Bedford Harbor, Outer New Bedford Harbor, Providence Harbor, Housatonic River, Norwalk Harbor, Little Neck Bay, Newark Bay, Sandy Hook Bay, Great Bay, Delaware Bay, Patuxent River and Crescent Beach. Poor correlations between ΣPBDE and lipids were

Progesterone and estradiol synergistically promote the lung metastasis of tuberin-deficient cells in a preclinical model of lymphangioleiomyomatosis

PubMed Central

Sun, Yang; Zhang, Erik; Lao, Taotao; Pereira, Ana M.; Li, Chenggang; Xiong, Li; Morrison, Tasha; Haley, Kathleen J.; Zhou, Xiaobo; Yu, Jane J.

2014-01-01

Lymphangioleiomyomatosis (LAM) is a female-predominant lung disease that can lead to respiratory failure. LAM cells typically have inactivating TSC2 mutations, leading to mTORC1 hyperactivation. The gender specificity of LAM suggests that female hormones contribute to disease progression. Clinical findings indicate that estradiol exacerbates LAM behaviors and symptoms. Although hormonal therapy with progesterone has been employed, the benefit in LAM improvement has not been achieved. We have previously found that estradiol promotes the survival and lung metastasis of cells lacking tuberin in a preclinical model of LAM. In this study, we hypothesize that progesterone alone or in combination with estradiol promote metastatic behaviors of TSC2-deficient cells. In cell culture models of TSC2-deficient LAM patient-derived and rat uterine leiomyoma-derived cells, we found that progesterone treatment or progesterone plus estradiol resulted in increased phosphorylation of Akt and ERK1/2, induced the proliferation, and enhanced the migration and invasiveness. In addition, treatment of progesterone plus estradiol synergistically decreased the levels of reactive oxygen species, and enhanced cell survival under oxidative stress. In a murine model of LAM, treatment of progesterone plus estradiol promoted the growth of xenograft tumors; however, progesterone treatment did not affect the development of xenograft tumors of Tsc2-deficient cells. Importantly, treatment of progesterone plus estradiol resulted in alteration of lung morphology, and significantly increased the number of lung micrometastases of Tsc2-deficient cells compared with estradiol treatment alone. Collectively, these data indicate that progesterone increases the metastatic potential of TSC2-deficient LAM patient-derived cells in vitro and lung metastasis in vivo. Thus, targeting progesterone-mediated signaling events may have therapeutic benefit for LAM and possibly other hormonally dependent cancers. PMID

Seasonal variability of polychlorinated biphenyls (PCBs) and polychlorinated diphenyl ethers (PBDEs) congener profiles in butter in Poland: dietary risk evaluation.

PubMed

Roszko, Marek; Szymczyk, Krystyna; Rzepkowska, Małgorzata; Jędrzejczak, Renata

2014-01-01

Various statistical methods have been employed to analyse in details seasonal diversification of polychlorinated biphenyl (PCB)/polybrominated diphenyl ether (PBDE) congener profiles found in butter fat. The variability of the PCB/PBDE congener profiles indicates the presence of various sources of the milk fat contamination. The obtained results suggest that the environmental chemical background has the highest share in the contamination sources pattern. Ion trap mass spectrometry coupled to high-resolution gas chromatography with semi-permeable membrane dialysis sample cleanup was used for determination of PCBs and PBDEs in milk fat. Determined butter fat PCB profiles were similar to the profiles characteristic for Aroclor 1254 technical mixture. Our data indicate that dietary intake of PCB/PBDE with milk and milk products may be estimated to be about 717.5 pg kg b.w.(-1) day(-1) for six-indicator PCBs, 0.329 (equivalent toxicity, TEQ) pg kg b.w.(-1) day(-1) for 12 DL PCBs and 50 pg kg b.w.(-1) day(-1) for PBDEs (sum of 14 congeners).

Long-Term Hematopoietic Engraftment of Congenic Amniotic Fluid Stem Cells After in Utero Intraperitoneal Transplantation to Immune Competent Mice

PubMed Central

Shangaris, Panicos; Loukogeorgakis, Stavros P.; Blundell, Michael P.; Petra, Eleni; Shaw, Steven W.; Ramachandra, Durrgah L.; Maghsoudlou, Panagiotis; Urbani, Luca; Thrasher, Adrian J.

2018-01-01

Clinical success of in utero transplantation (IUT) using allogeneic hematopoietic stem cells (HSCs) has been limited to fetuses that lack an immune response to allogeneic cells due to severe immunological defects, and where transplanted genetically normal cells have a proliferative or survival advantage. Amniotic fluid (AF) is an autologous source of stem cells with hematopoietic potential that could be used to treat congenital blood disorders. We compared the ability of congenic and allogeneic mouse AF stem cells (AFSC) to engraft the hematopoietic system of time-mated C57BL/6J mice (E13.5). At 4 and 16 weeks of age, multilineage donor engraftment was higher in congenic versus allogeneic animals. In vitro mixed lymphocyte reaction confirmed an immune response in the allogeneic group with higher CD4 and CD8 cell counts and increased proliferation of stimulated lymphocytes. IUT with congenic cells resulted in 100% of donor animals having chimerism of around 8% and successful hematopoietic long-term engraftment in immune-competent mice when compared with IUT with allogeneic cells. AFSCs may be useful for autologous cell/gene therapy approaches in fetuses diagnosed with congenital hematopoietic disorders. PMID:29482456

MOLECULAR PROBES FOR MUSCARINIC RECEPTORS: FUNCTIONALIZED CONGENERS OF SELECTIVE MUSCARINIC ANTAGONISTS

PubMed Central

Jacobson, Kenneth A.; Fischer, Bilha; van Rhee, A. Michiel

2012-01-01

Summary The muscarinic agonist oxotremorine and the tricyclic muscarinic antagonists pirenzepine and telenzepine have been derivatized using a functionalized congener approach for the purpose of synthesizing high affinity ligand probes that are suitable for conjugation with prosthetic groups, for receptor cross-linking, fluorescent and radioactive detection, etc. A novel fluorescent conjugate of TAC (telenzepine amine congener), an n-decylamino derivative of the ml-selective antagonist, with the fluorescent trisulfonated pyrene dye Cascade Blue may be useful for assaying the receptor as an alternative to radiotracers. In a rat m3 receptor mutant containing a single amino acid substitution in the sixth transmembrane domain (Asn507 to Ala) the parent telenzepine lost 636-fold in affinity, while TAC lost only 27-fold. Thus, the decylamino group of TAC stabilizes the bound state and thus enhances potency by acting as a distal anchor in the receptor binding site. We have built a computer-assisted molecular model of the transmembrane regions of muscarinic receptors based on homology with the G-protein coupled receptor rhodopsin, for which a low resolution structure is known. We have coordinated the antagonist pharmacophore (tricyclic and piperazine moieties) with residues of the third and seventh helices of the rat m3 receptor. Although the decylamino chain of TAC is likely to be highly flexible and may adopt many conformations, we located one possible site for a salt bridge formation with the positively charged −NH3+ group, i.e. Asp113 in helix II. PMID:10188781

Nomegestrol acetate-17b-estradiol for oral contraception

PubMed Central

Burke, Anne

2013-01-01

Oral contraceptives remain a popular method of contraception over 50 years after their introduction. While safe and effective for many women, the failure rate of oral contraception is about 8%. Concerns about the risk of venous thromboembolism continue to drive the search for the safest oral contraceptive formulations. The oral contraceptive NOMAC-E2 contains nomegestrol acetate (NOMAC) 2.5 mg + 17b-estradiol (E2) 1.5 mg. The approved dosing regimen is 24 days of active hormone, followed by a 4-day hormone-free interval. NOMAC is a progestin derived from testosterone, which has high bioavailability, rapid absorption, and a long half-life. Estradiol, though it has a lower bioavailability, has been successfully combined with NOMAC in a monophasic oral contraceptive. Two recently published randomized controlled trials demonstrate that NOMAC-E2 is an effective contraceptive, with a Pearl Index less than one pregnancy per 100 woman-years. The bleeding pattern on NOMAC-E2 is characterized by fewer bleeding/spotting days, shorter withdrawal bleeds, and a higher incidence of amenorrhea than the comparator oral contraceptive containing drospirenone and ethinyl estradiol. The adverse event profile appears to be acceptable. Few severe adverse events were reported in the randomized controlled trials. The most common adverse events were irregular bleeding, acne, and weight gain. Preliminary studies suggest that NOMAC-E2 does not seem to have negative effects on hemostatic and metabolic parameters. While no one oral contraceptive formulation is likely to be the optimum choice for all women, NOMAC-E2 is a formulation with effectiveness comparable with that of other oral contraceptives, and a reassuring safety profile. PMID:23836965

[Co-administration of RJR-2403 with low dose of 17beta-estradiol on spatial learning in ovariectomized rats].

PubMed

Fedotova, Yu O

2013-01-01

The aim of this work was to study the influence of stimulation or blockade Nalpha7-cholinoreceptors on dynamics of spatial learning in water Morris maze and on behavior in the "open field" test in adult ovariectomized (OVX) females given with a low dose of 17beta-estradiol. Agonist of Nalpha7-cholinoreceptors - RJR-2403 (1.0 mg/kg, i.p.) or antagonist of Nalpha7-cholinoreceptors - mecamylamine (1.0 mg/kg, i.p.) treated chronically (14 days) alone and in a combination with low dose of 17beta-estradiol (0.5 micro/rat, s.c.) to OVX rats. Co-administration of RJR-2403 with low dose of 17beta-estradiol completely restored impaired spatial learning in water Morris maze in OVX females. Moreover, OVX rats treated with RJR-2403 and low dose of 17beta-estradiol demonstrated increased exploratory and grooming behavior in the "open field" test. Both mecamylamine alone and in combination with low dose of 17beta-estradiol failed to influence on spatial learning and failed to modify behavior in the "open field" test in OVX rats. The results of the present study suggest a positive effect of RJR-2403 in combination with low dose of 17beta-estradiol on spatial learning at estrogen deficiency.

A continuous regimen of levonorgestrel/ethinyl estradiol for contraception and elimination of menstruation.

PubMed

Jensen, Jeffrey T

2008-03-01

Clinicians and patients desiring amenorrhea for therapeutic or social reasons will find continuous-use 90 microg levonorgestrel/20 microg ethinyl estradiol to be an attractive oral contraceptive dosing option. Although other formulations of oral contraceptives can be dosed in a continuous manner off-label, the convenience of a 28-day dose pack represents a major advance that will likely increase acceptability of the strategy. The availability of FDA-approved continuous-use 90 microg levonorgestrel/20 microg ethinyl estradiol will help mainstream continuous oral contraception in the same way that Preven and Plan B helped legitimize and mainstream emergency contraception. Patients wishing to use continuous 90 microg levonorgestrel/20 microg ethinyl estradiol must recognize and accept that unscheduled breakthrough bleeding is typical during the first four to six cycles of use. Control of cycle-related symptoms may emerge as an off-label indication for use.

Vocal Acoustic and Auditory-Perceptual Characteristics During Fluctuations in Estradiol Levels During the Menstrual Cycle: A Longitudinal Study.

PubMed

Arruda, Polyanna; Diniz da Rosa, Marine Raquel; Almeida, Larissa Nadjara Alves; de Araujo Pernambuco, Leandro; Almeida, Anna Alice

2018-03-07

Estradiol production varies cyclically, changes in levels are hypothesized to affect the voice. The main objective of this study was to investigate vocal acoustic and auditory-perceptual characteristics during fluctuations in the levels of the hormone estradiol during the menstrual cycle. A total of 44 volunteers aged between 18 and 45 were selected. Of these, 27 women with regular menstrual cycles comprised the test group (TG) and 17 combined oral contraceptive users comprised the control group (CG). The study was performed in two phases. In phase 1, anamnesis was performed. Subsequently, the TG underwent blood sample collection for measurement of estradiol levels and voice recording for later acoustic and auditory-perceptual analysis. The CG underwent only voice recording. Phase 2 involved the same measurements as phase 1 for each group. Variables were evaluated using descriptive and inferential analysis to compare groups and phases and to determine relationships between variables. Voice changes were found during the menstrual cycle, and such changes were determined to be related to variations in estradiol levels. Impaired voice quality was observed to be associated with decreased levels of estradiol. The CG did not demonstrate significant vocal changes during phases 1 and 2. The TG showed significant increases in vocal parameters of roughness, tension, and instability during phase 2 (the period of low estradiol levels) when compared with the CG. Low estradiol levels were also found to be negatively correlated with the parameters of tension, instability, and jitter and positively correlated with fundamental voice frequency. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Estradiol and GPER Activation Differentially Affect Cell Proliferation but Not GPER Expression in the Hippocampus of Adult Female Rats.

PubMed

Duarte-Guterman, Paula; Lieblich, Stephanie E; Chow, Carmen; Galea, Liisa A M

2015-01-01

Estradiol increases cell proliferation in the dentate gyrus of the female rodent but it is not known whether the G protein-coupled estrogen receptor (GPER), a membrane receptor, is involved in this process, nor whether there are regional differences in estradiol's effects on cell proliferation. Thus, we investigated whether estradiol exerts its effects on cell proliferation in the dorsal and ventral dentate gyrus through GPER, using the GPER agonist, G1, and antagonist, G15. Ovariectomized adult female rats received a single injection of either: 17β-estradiol (10 μg), G1 (0.1, 5, 10 μg), G15 (40 μg), G15 and estradiol, or vehicle (oil, DMSO, or oil+DMSO). After 30 min, animals received an injection of bromodeoxyuridine (BrdU) and were perfused 24 h later. Acute treatment with estradiol increased, while the GPER agonist G1 (5 μg) decreased, the number of BrdU+ cells in the dentate gyrus relative to controls. The GPER antagonist, G15 increased the number of BrdU+ cells relative to control in the dorsal region and decreased the number of BrdU+ cells in the ventral region. However, G15 treatment in conjunction with estradiol partially eliminated the estradiol-induced increase in cell proliferation in the dorsal dentate gyrus. Furthermore, G1 decreased the expression of GPER in the dentate gyrus but not the CA1 and CA3 regions of the hippocampus. In summary, we found that activation of GPER decreased cell proliferation and GPER expression in the dentate gyrus of young female rats, presenting a potential and novel estrogen-independent role for this receptor in the adult hippocampus.

Estradiol modulates neural response to conspecific and heterospecific song in female house sparrows: An in vivo positron emission tomography study

PubMed Central

Stabile, Frank A.; Carson, Richard E.

2017-01-01

Although there is growing evidence that estradiol modulates female perception of male sexual signals, relatively little research has focused on female auditory processing. We used in vivo 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging to examine the neuronal effects of estradiol and conspecific song in female house sparrows (Passer domesticus). We assessed brain glucose metabolism, a measure of neuronal activity, in females with empty implants, estradiol implants, and empty implants ~1 month after estradiol implant removal. Females were exposed to conspecific or heterospecific songs immediately prior to imaging. The activity of brain regions involved in auditory perception did not differ between females with empty implants exposed to conspecific vs. heterospecific song, but neuronal activity was significantly reduced in females with estradiol implants exposed to heterospecific song. Furthermore, our within-individual design revealed that changes in brain activity due to high estradiol were actually greater several weeks after peak hormone exposure. Overall, this study demonstrates that PET imaging is a powerful tool for assessing large-scale changes in brain activity in living songbirds, and suggests that after breeding is done, specific environmental and physiological cues are necessary for estradiol-stimulated females to lose the selectivity they display in neural response to conspecific song. PMID:28832614

First trimester β-hCG and estradiol levels in singleton and twin pregnancies after assisted reproduction.

PubMed

Póvoa, Ana; Xavier, Pedro; Matias, Alexandra; Blicksttein, Isaac

2017-07-28

To compare levels of β-hCG and estradiol collected during the first trimester in singleton and twin pregnancies following assisted reproduction technologies (ART). We prospectively evaluated 50 singleton and 47 dichorionic twin pregnancies that eventually ended in live births. Patients were recruited from a single ART center with standard treatment protocols followed by fresh embryo transfers. Hormone measurements were performed within a narrow gestational age range and analyzed in a single laboratory thus minimizing inter- and intra-assay variability. We measured serum β-hCG at 13 days after embryo transfer as well as samples of β-hCG and estradiol at 8-9 weeks+6 days. No significant differences existed between singletons and twins in respect to demographic and cycle characteristics. β-hCG and estradiol were all significantly higher in twins (P<0.05). The data confirms the higher levels of β-hCG and estradiol in twins, pointing to the potential role of these placental hormones in early support of a twin pregnancy.

Simultaneous total occlusion of two coronary arteries associated with use of drospirenone-ethinyl estradiol (oral contraceptive).

PubMed

Atmaca, Hüsnü; Köprülü, Diyar; Kiriş, Tuncay; Zeren, Gönül; Şahin, İrfan

2018-01-01

Although the use of oral contraceptives is associated with an increased risk of venous thromboembolic disease, the risk of myocardial infarction (MI) is unclear. A new, third-generation contraceptive agent, drospirenone-ethinyl estradiol, which contains less estrogen and a new progestogen, drospirenone, in a different combination, has been considered more reliable in terms of risk of MI. However, there have been some cases of MI associated with the use of drospirenone-ethinyl estradiol, despite the protective effects of this oral contraceptive. In this report, a 33-year-old woman who had used drospirenone-ethinyl estradiol for 6 months was admitted with MI and symptoms of cardiogenic shock. Coronary angiography revealed the total occlusion of 2 coronary arteries and so percutaneous coronary intervention was performed. To the best of our knowledge, this is the first case report of simultaneous total occlusion of 2 coronary arteries associated with the use of drospirenone-ethinyl estradiol in the English-language medical literature.

Estradiol Therapy After Menopause Mitigates Effects of Stress on Cortisol and Working Memory.

PubMed

Herrera, Alexandra Ycaza; Hodis, Howard N; Mack, Wendy J; Mather, Mara

2017-12-01

Postmenopausal estradiol therapy (ET) can reduce the stress response. However, it remains unclear whether such reductions can mitigate effects of stress on cognition. Investigate effects of ET on cortisol response to a physical stressor, cold pressor test (CPT), and whether ET attenuates stress effects on working memory. Women completed the CPT or control condition across two sessions and subsequently completed a sentence span task. General community: Participants were recruited from the Early vs Late Intervention Trial with Estradiol (ELITE). ELITE participants (mean age = 66, standard deviation age = 6.8) in this study did not suffer from any major chronic illness or use medications known to affect the stress response or cognition. Participants had received a median of randomized 4.7 years of estradiol (n = 21) or placebo (n = 21) treatment at time of participation in this study. Salivary cortisol and sentence span task performance. Women assigned to estradiol exhibited blunted cortisol responses to CPT compared with placebo (P = 0.017) and lesser negative effects of stress on working memory (P = 0.048). We present evidence suggesting ET may protect certain types of cognition in the presence of stress. Such estrogenic protection against stress hormone exposure may prove beneficial to both cognition and the neural circuitry that maintains and propagates cognitive faculties. Copyright © 2017 Endocrine Society

Di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate inhibit growth and reduce estradiol levels of antral follicles in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Rupesh K., E-mail: drrupesh@illinois.ed; Singh, Jeffery M., E-mail: jsingh20@illinois.ed; Leslie, Tracie C., E-mail: tleslie2@illinois.ed

2010-01-15

Any insult that affects survival of ovarian antral follicles can cause abnormal estradiol production and fertility problems. Phthalate esters (PEs) are plasticizers used in a wide range of consumer and industrial products. Exposure to these chemicals has been linked to reduced fertility in humans and animal models. Di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) decrease serum estradiol levels and aromatase (Arom) expression, prolong estrous cycles, and cause anovulation in animal and culture models. These observations suggest PEs directly target antral follicles. We therefore tested the hypothesis that DEHP (1-100 mug/ml) and MEHP (0.1-10 mug/ml) directly inhibit antral follicular growth andmore » estradiol production. Antral follicles from adult mice were cultured with DEHP or MEHP, and/or estradiol for 96 h. During culture, follicle size was measured every 24 h as a measurement of follicle growth. After culture, media were collected for measurement of estradiol levels and follicles were subjected to measurement of cylin-D-2 (Ccnd2), cyclin-dependant-kinase-4 (Cdk4), and Arom. We found that DEHP and MEHP inhibited growth of follicles and decreased estradiol production compared to controls at the highest doses. DEHP and MEHP also decreased mRNA expression of Ccnd2, Cdk4, and Arom at the highest dose. Addition of estradiol to the culture medium prevented the follicles from DEHP- and MEHP-induced inhibition of growth, reduction in estradiol levels, and decreased Ccnd2 and Cdk4 expression. Collectively, our results indicate that DEHP and MEHP may directly inhibit antral follicle growth via a mechanism that partially includes reduction in levels of estradiol production and decreased expression of cell cycle regulators.« less

Age trends in estradiol and estrone levels measured using liquid chromatography tandem mass spectrometry in community-dwelling men of the Framingham Heart Study.

PubMed

Jasuja, Guneet Kaur; Travison, Thomas G; Davda, Maithili; Murabito, Joanne M; Basaria, Shehzad; Zhang, Anqi; Kushnir, Mark M; Rockwood, Alan L; Meikle, Wayne; Pencina, Michael J; Coviello, Andrea; Rose, Adam J; D'Agostino, Ralph; Vasan, Ramachandran S; Bhasin, Shalender

2013-06-01

Age trends in estradiol and estrone levels in men and how lifestyle factors, comorbid conditions, testosterone, and sex hormone-binding globulin affect these age trends remain poorly understood, and were examined in men of the Framingham Heart Study. Estrone and estradiol concentrations were measured in morning fasting samples using liquid chromatography tandem mass spectrometry in men of Framingham Offspring Generation. Free estradiol was calculated using a law of mass action equation. There were 1,461 eligible men (mean age [±SD] 61.1±9.5 years and body mass index [BMI] 28.8±4.5kg/m(2)). Total estradiol and estrone were positively associated with age, but free estradiol was negatively associated with age. Age-related increase in total estrone was greater than that in total estradiol. Estrone was positively associated with smoking, BMI, and testosterone, and total and free estradiol with diabetes, BMI, testosterone, and comorbid conditions; additionally, free estradiol was associated negatively with smoking. Collectively, age, BMI, testosterone, and other health and behavioral factors explained only 18% of variance in estradiol, and 9% of variance in estrone levels. Men in the highest quintile of estrone levels had significantly higher age and BMI, and a higher prevalence of smoking, diabetes, and cardiovascular disease than others, whereas those in the highest quintile of estradiol had higher BMI than others. Total estrone and estradiol levels in men, measured using liquid chromatography tandem mass spectrometry, revealed significant age-related increases that were only partially accounted for by cross-sectional differences in BMI, diabetes status, and other comorbidities and health behaviors. Longitudinal studies are needed to confirm these findings.

Quantifying the Role of Circulating Unconjugated Estradiol in Mediating the Body Mass Index-Breast Cancer Association.

PubMed

Schairer, Catherine; Fuhrman, Barbara J; Boyd-Morin, Jennifer; Genkinger, Jeanine M; Gail, Mitchell H; Hoover, Robert N; Ziegler, Regina G

2016-01-01

Higher body mass index (BMI) and circulating estrogen levels each increase postmenopausal breast cancer risk, particularly estrogen receptor-positive (ER(+)) tumors. Higher BMI also increases estrogen production. We estimated the proportion of the BMI-ER(+) breast cancer association mediated through estrogen in a case-control study nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Participants included 143 women with invasive ER(+) breast cancer and 268 matched controls, all postmenopausal and never having used hormone therapy at baseline. We used liquid chromatography-tandem mass spectrometry to measure 15 estrogens and estrogen metabolites in baseline serum. We calculated BMI from self-reported height and weight at baseline. We estimated the mediating effect of unconjugated estradiol on the BMI-ER(+) breast cancer association using Aalen additive hazards and Cox regression models. All estrogens and estrogen metabolites were statistically significantly correlated with BMI, with unconjugated estradiol most strongly correlated [Pearson correlation (r) = 0.45]. Approximately 7% to 10% of the effect of overweight, 12% to 15% of the effect of obesity, and 19% to 20% of the effect of a 5 kg/m(2) BMI increase on ER(+) breast cancer risk was mediated through unconjugated estradiol. The BMI-breast cancer association, once adjusted for unconjugated estradiol, was not modified by further adjustment for two metabolic ratios statistically significantly associated with both breast cancer and BMI. Circulating unconjugated estradiol levels partially mediate the BMI-breast cancer association, but other potentially important estrogen mediators (e.g., bioavailable estradiol) were not evaluated. Further research is required to identify mechanisms underlying the BMI-breast cancer association. ©2015 American Association for Cancer Research.

The Effect of Supraphysiological Estradiol on Pregnancy Outcomes Differs between Women with PCOS and Ovulatory Women.

PubMed

Wei, Daimin; Yu, Yunhai; Sun, Mei; Shi, Yuhua; Sun, Yun; Deng, Xiaohui; Li, Jing; Wang, Ze; Zhao, Shigang; Zhang, Heping; Legro, Richard S; Chen, Zi-Jiang

2018-04-27

Supra-physiological estradiol exposure after ovarian stimulation may disrupt embryo implantation after fresh embryo transfer, compared with physiological estradiol exposure during frozen embryo transfer(FET). Women with polycystic ovary syndrome (PCOS) who usually over-respond to ovarian stimulation have a better live birth rate after elective FET than fresh embryo transfer; however ovulatory women don't. To evaluate whether the discrepancy in live birth rate after fresh versus FET between women with PCOS and ovulatory women was due to the variation in ovarian response, i.e. peak estradiol level or oocyte number. This was a secondary analysis of data from two multicenter randomized trials with similar study designs. A total of 1508 women with PCOS in the first trial and 2157 ovulatory women in the second trial were randomized to undergo either fresh or frozen embryo transfer. The primary outcome was live birth. Compared with fresh embryo transfer, FET resulted in a higher live birth rate(51.9% vs. 40.7%, OR: 1.57, 95%CI: 1.22-2.03) in PCOS women with peak estradiol level >3000pg/ml but not in those with estradiol level ≤3000pg/ml. In PCOS women with oocyte number ≥16, FET yielded a higher live birth rate(54.8% vs. 42.1%, OR: 1.67, 95%CI: 1.20-2.31), but not in those with oocyte number <16. However, in ovulatory women, the pregnancy outcomes were comparable after fresh and FET in all subgroups. Supra-physiological level of estradiol after ovarian stimulation may adversely affect pregnancy outcomes in women with PCOS; but not in ovulatory women.

Dahl (S × R) Rat Congenic Strain Analysis Confirms and Defines a Chromosome 17 Spatial Navigation Quantitative Trait Locus to <10 Mbp

PubMed Central

Herrera, Victoria L.; Pasion, Khristine A.; Tan, Glaiza A.; Ruiz-Opazo, Nelson

2013-01-01

A quantitative trait locus (QTL) linked with ability to find a platform in the Morris Water Maze (MWM) was located on chromosome 17 (Nav-5 QTL) using intercross between Dahl S and Dahl R rats. We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL. Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02). The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02–74.66 Mbp region. Additional fine mapping is necessary to identify the specific gene variant accounting for Nav-5 effect on spatial learning and memory in Dahl rats. PMID:23469157

Dahl (S × R) rat congenic strain analysis confirms and defines a chromosome 17 spatial navigation quantitative trait locus to <10 Mbp.

PubMed

Herrera, Victoria L; Pasion, Khristine A; Tan, Glaiza A; Ruiz-Opazo, Nelson

2013-01-01

A quantitative trait locus (QTL) linked with ability to find a platform in the Morris Water Maze (MWM) was located on chromosome 17 (Nav-5 QTL) using intercross between Dahl S and Dahl R rats. We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL. Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02). The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02-74.66 Mbp region. Additional fine mapping is necessary to identify the specific gene variant accounting for Nav-5 effect on spatial learning and memory in Dahl rats.

The effects of an environmentally relevant 58-congener polychlorinated biphenyl (PCB) mixture on cardiac development in the chick embryo.

PubMed

Carro, Tiffany; Taneyhill, Lisa A; Ann Ottinger, Mary

2013-06-01

Chicken (Gallus domesticus) embryonic exposure in ovo to a 58-congener polychlorinated biphenyl (PCB) mixture resulted in teratogenic heart defects in chick embryos at critical heart developmental stages Hamburger-Hamilton (HH) stages 10, 16, and 20. The 58-congener mixture contained relative proportions of primary congeners measured in belted sandpiper (Megaceryle alcyon) and spotted sandpiper (Actitis macularia) eggs collected along the upper Hudson River, New York, USA, and chicken doses were well below observed environmental exposure levels. Embryos were injected with 0.08 µg PCBs/g egg weight and 0.50 µg PCBs/g egg weight (0.01 and 0.064 ng toxic equivalent/g, respectively) at embryonic day 0, prior to incubation. Mortality of exposed embryos was increased at all developmental stages, with a marked rise in cardiomyopathies at HH16 and HH20 (p < 0.05). Heart abnormalities occurred across all treatments, including abnormal elongation and expansion of the heart tube at HH10, improper looping and orientation, indentations in the emerging ventricular wall (HH16 and HH20), and irregularities in overall heart shape (HH10, HH16, and HH20). Histology was conducted on 2 cardiac proteins critical to embryonic heart development, ventricular myosin heavy chain and titin, to investigate potential mechanistic effects of PCBs on heart development, but no difference was observed in spatiotemporal expression. Similarly, cellular apoptosis in the developing heart was not affected by exposure to the PCB mixture. Conversely, cardiomyocyte proliferation rates dramatically declined (p < 0.01) at HH16 and HH20 as PCB exposure concentrations increased. Early embryonic cardiomyocyte proliferation contributes to proper formation of the morphology and overall thickness of the ventricular wall. Therefore, in ovo exposure to this 58-congener PCB mixture at critical stages adversely affects embryonic heart development. Copyright © 2013 SETAC.

Effects of 17β-estradiol on emissions of greenhouse gases in simulative natural water body.

PubMed

Ruan, Aidong; Zhao, Ying; Liu, Chenxiao; Zong, Fengjiao; Yu, Zhongbo

2015-05-01

Environmental estrogens are widely spread across the world and are increasingly thought of as serious contaminators. The present study looks at the influence of different concentrations of 17β-estradiol on greenhouse gas emissions (CO2 , CH4 , and N2 O) in simulated systems to explore the relationship between environmental estrogen-pollution and greenhouse gas emissions in natural water bodies. The present study finds that 17β-estradiol pollution in simulated systems has significant promoting effects on the emissions of CH4 and CO2 , although no significant effects on N2 O emissions. The present study indicates that 17β-estradiol has different effects on the different elements cycles; the mechanism of microbial ecology is under review. © 2015 SETAC.

17β-estradiol rapidly facilitates lordosis through G protein-coupled estrogen receptor 1 (GPER) via deactivation of medial preoptic nucleus μ-opioid receptors in estradiol primed female rats.

PubMed

Long, Nathan; Serey, Chhorvann; Sinchak, Kevin

2014-09-01

In female rats sexual receptivity (lordosis) can be induced with either a single large dose of estradiol benzoate (EB), or a priming dose of EB that does not induce sexual receptivity followed by 17β-estradiol (E2). Estradiol priming initially inhibits lordosis through a multi-synaptic circuit originating in the arcuate nucleus of the hypothalamus (ARH) that activates and internalizes μ-opioid receptors (MOR) in medial preoptic nucleus (MPN) neurons. Lordosis is facilitated when MPN MOR are deactivated after the initial estradiol-induced activation. We tested the hypothesis that E2 given 47.5 h post EB acts rapidly through G protein-coupled estrogen receptor 1 (GPER) in the ARH to deactivate MPN MOR and facilitate lordosis. Ovariectomized Long Evans rats implanted with a third ventricle cannula were primed with 2 μg EB. DMSO control, E2, or G1 (GPER selective agonist) was infused 47.5 h later, and rats were tested for sexual receptivity. E2 and G1 infusions significantly increased levels of sexual receptivity compared to DMSO controls and pretreatment with G15 (GPER antagonist) blocked the facilitation of sexual receptivity. Brains were processed for MPN MOR immunohistochemistry to measure MPN MOR activation levels. E2 and G1 both significantly reduced MPN MOR activation compared to DMSO controls, while pretreatment with G15 blocked MPN MOR deactivation. In another group of EB treated ovariectomized rats, GPER immunofluorescence positive staining was observed throughout the ARH. Together these data indicate that in the 2 μg EB primed rat, E2 rapidly signals through GPER in the ARH to deactivate MPN MOR and facilitate lordosis. Published by Elsevier Inc.

A 14-gene region of rat chromosome 8 in SHR-derived polydactylous congenic substrain affects muscle-specific insulin resistance, dyslipidaemia and visceral adiposity.

PubMed

Seda, O; Liska, F; Sedová, L; Kazdová, L; Krenová, D; Kren, V

2005-01-01

The SHR and the PD/Cub are two established rodent models of human metabolic syndrome. Introgression of a ca 30 cM region of rat chromosome 8 from PD/Cub onto the genetic background of SHR was previously shown to influence several of the metabolic syndrome-related traits along with causing the PLS in the SHR-Lx congenic strain. In the process of identification of the causative alleles, we have produced several congenic sublines. The differential segment of SHR-Lx PD5 congenic substrain [SHR.PD(D8Rat42-D8Arb23)/Cub] spans approximately 1.4 Mb encompassing only 14 genes. When comparing the metabolic, morphometric and gene expression profiles of the SHR-Lx PD5 vs. SHR, the polydactyly and several distinct metabolic features observed in the original SHR-Lx congenic were still manifested, suggesting that the responsible genes were "trapped" within the relatively short differential segment of PD/Cub origin in SHR-Lx PD5. Particularly, the SHR-Lx PD5 displayed substantial reduction of insulin sensitivity confined to skeletal muscle. Among the candidate genes, the promyelocytic leukaemia zinc-finger Plzf (Zbtb16) transcription repressor is most likely responsible for the Lx mutation resulting in PLS and could also be involved in the alteration of metabolic pathways. The sequence analysis of the Plzf gene revealed a SNP leading to a threonine to serine substitution in SHR at aminoacid position 208 (T208S). In summary, we have isolated a 1.4 Mb genomic region syntenic to human chromosome 11q23, which, apart from causing polydactyly-luxate syndrome (PLS), affects total body weight, adiposity, lipid profile, insulin sensitivity of skeletal muscle and related gene expression as shown in the SHR-Lx PD5 congenic substrain.

Modulation of hepatocyte growth factor secretion in human female reproductive tract stromal fibroblasts by poly (I:C) and estradiol.

PubMed

Coleman, Kimberly D; Ghosh, Mimi; Crist, Sarah G; Wright, Jacqueline A; Rossoll, Richard M; Wira, Charles R; Fahey, John V

2012-01-01

Hepatocyte Growth Factor (HGF) secretion facilitates epithelial cell growth and development in the female reproductive tract (FRT) and may contribute to pathological conditions such as cancer and endometriosis. We hypothesized that estradiol and poly (I:C), a synthetic RNA mimic, may have a regulatory effect on HGF secretion by stromal fibroblasts from FRT tissues. Following hysterectomies, normal tissue from the uterus, endocervix, and ectocervix were dispersed into stromal cell fractions by enzymatic digestion and differential filtering. Stromal fibroblasts were cultured and treated with estradiol and/or poly (I:C), and conditioned media were analyzed for HGF via enzyme-linked immunosorbent assay. Treating uterine fibroblasts with estradiol or poly (I:C) significantly increased HGF secretion. When uterine fibroblasts were co-treated with estradiol and poly (I:C), the effect on HGF secretion was additive. In contrast, stromal fibroblasts from endo- and ecto-cervix were unresponsive to estradiol, but were stimulated to secrete HGF by poly (I:C). HGF secretion is uniquely regulated in the uterus, but not in ecto- and endo-cervix, by estradiol. Moreover, potential viral pathogens further induce HGF. These findings have potential applications in understanding both hormonal regulation of normal tissue as well as the role of HGF in tumorogenesis, endometriosis, and human immunodeficiency virus infection. © 2011 John Wiley & Sons A/S.

Control of follicle-stimulating hormone by estradiol and the inhibins: critical role of estradiol at the hypothalamus during the luteal-follicular transition.

PubMed

Welt, Corrine K; Pagan, Yanira L; Smith, Patricia C; Rado, Kimberly B; Hall, Janet E

2003-04-01

To test the hypothesis that estradiol, inhibin A, and inhibin B contribute differentially to FSH negative feedback in specific phases of the menstrual cycle, daily blood samples were obtained across a control cycle and after selective estrogen blockade with tamoxifen. To examine the site of estradiol-negative feedback in control and tamoxifen treatment cycles, early follicular phase GnRH (free alpha-subunit) pulse frequency was assessed in normal women, and FSH levels were examined in GnRH-deficient women in whom hypothalamic output was fixed with GnRH administration. FSH was higher in the early follicular phase in the presence of estrogen receptor blockade (15.7 +/- 3.1 vs. 13.2 +/- 1.9 IU/liter; P < 0.05) but was not increased in the late follicular phase. In the luteal phase, FSH was elevated (10.1 +/- 0.7 vs. 7.3 +/- 0.6 IU/liter; P < 0.01). In normal women, free alpha-subunit pulse frequency increased (7.3 +/- 0.4 vs. 4.8 +/- 0.4 pulses per 8 h; P < 0.003), but in GnRH-deficient women, there was no FSH increase (11.1 +/- 1.6 vs. 12.5 +/- 3.6 IU/liter) in the early follicular phase in the presence of estrogen blockade. In conclusion, estradiol exerts a greater role over inhibin in FSH-negative feedback regulation during the luteal phase and the luteal-follicular transition. In contrast, inhibin A and/or B plays a more critical role as the follicular phase progresses. In addition, these studies support a primary if not exclusive hypothalamic site of estrogen-negative feedback in the early follicular phase.

Complex Actions of Estradiol-3-Sulfate in Late Gestation Fetal Brain

PubMed Central

Winikor, Jared; Schlaerth, Christine; Rabaglino, Maria Belen; Cousins, Roderick; Sutherland, Monique

2011-01-01

The most abundant form of estrogen circulating in fetal plasma is sulfo-conjugated estrogen; for example, estradiol-3-sulfate (E2SO4) is more highly abundant than estradiol (E2). The present study investigated the ontogeny of the deconjugating (steroid sulfatase [STS]) and conjugating (estrogen sulfotransferase [STF]) enzymes in ovine fetal brain and tested the hypothesis that treatment with E2SO4 would alter the expression of one or both enzymes. Steroid sulfatase was more highly expressed than STF, and both changed as a function of gestational age. Estradiol-3-sulfate infused intracerebroventricularly (icv) significantly increased plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations. Plasma E2 and E2SO4 were increased, and brain expression of estrogen receptor α was decreased. The proteins STS and STF were up- and downregulated, respectively. Pituitary proopiomelanocortin (POMC) and follicle-stimulating hormone (FSH) and hypothalamic corticotrophin-releasing hormone (CRH) messenger RNA (mRNA) was decreased. We conclude that E2SO4 has complex actions on the fetal brain, which might involve deconjugation by STS, but that the net result of direct E2SO4 icv infusion is more complex than can be accounted for by infusion of E2 alone. PMID:21273638

Distinguishing PCB Isomeric Congeners with their Gas Chromatographic and Mass Spectrometric Ortho Effect using Comprehensive Gas Chromatography

EPA Science Inventory

The 209 polychlorinated biphenyl (PCB) congeners and associated nine isomeric groups (nine groups of PCBs with the same degree of chlorination) have been long recorded as high endocrine disrupting chemicals in the environment. Difficult analytical problems exist, in those frequen...

17-β-Estradiol induces spreading depression and pain behavior in alert female rats

PubMed Central

Sandweiss, Alexander J.; Cottier, Karissa E.; McIntosh, Mary I.; Dussor, Gregory; Davis, Thomas P.; Vanderah, Todd W.; Largent-Milnes, Tally M.

2017-01-01

Aims Test the putative contribution of 17-β-estradiol in the development of spreading depression (SD) events and head pain in awake, non-restrained rats. Main Methods Female, Sprague-Dawley rats were intact or underwent ovariectomy followed one week later by surgery to place electrodes onto the dura to detect epidural electroencephalographic activity (dEEG). dEEG activity was recorded two days later for 12 hours after systemic administration of 17-β-estradiol (180 μg/kg, i.p.). A separate set of rats were observed for changes in exploratory, ambulatory, fine, and rearing behaviors; periorbital allodynia was also assessed. Key Findings A bolus of 17-β-estradiol significantly elevated serum estrogen levels, increased SD episodes over a 12-hour recording period and decreased rearing behaviors in ovariectomized rats. Pre-administration of ICI 182,780, an estrogen receptor antagonist, blocked 17-β-estradiol-evoked SD events and pain behaviors; similar results were observed when the antimigraine therapeutic sumatriptan was used. Significance These data indicate that an estrogen receptor-mediated mechanism contributes to SD events in ovariectomized rats and pain behaviors in both ovariectomized -and intact- rats. This suggests that estrogen plays a different role in each phenomenon of migraine where intense fluctuations in concentration may influence SD susceptibility. This is the first study to relate estrogen peaks to SD development and pain behaviors in awake, freely moving female rats, establishing a framework for future preclinical migraine studies. PMID:29371973

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.

PubMed

Szalay, László; Shimizu, Tomoharu; Suzuki, Takao; Yu, Huang-Ping; Choudhry, Mashkoor A; Schwacha, Martin G; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

2006-03-01

Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

Naproxen or Estradiol for Bleeding and Spotting with the Levonorgestrel Intrauterine System: A Randomized Controlled Trial

PubMed Central

MADDEN, Tessa; PROEHL, Sarah; ALLSWORTH, Jenifer E.; SECURA, Gina M.; PEIPERT, Jeffrey F.

2011-01-01

Objective To evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women initiating the levonorgestrel-releasing intrauterine system (LNG-IUS). Study Design We conducted a randomized controlled trial of naproxen, estradiol, or placebo administered over the first 12 weeks of LNG-IUS use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis. Results There were 129 women randomized to naproxen (n=42), estradiol (n=44), or placebo (n=43). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared to placebo, 42.9% versus 16.3% (p=0.03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (RRadj 0.90, 95%CI 0.84–0.97) compared to placebo. More frequent bleeding and spotting was observed in the estradiol group (RRadj 1.25, 95%CI 1.17–1.34). Conclusions Administration of naproxen resulted in a reduction in bleeding and spotting days compared to placebo. (150 words) PMID:22055339

17β-Estradiol augments antidepressant efficacy of escitalopram in ovariectomized rats: Neuroprotective and serotonin reuptake transporter modulatory effects.

PubMed

Ibrahim, Weam W; Safar, Marwa M; Khattab, Mahmoud M; Agha, Azza M

2016-12-01

The prevalence or recurrence of depression is seriously increased in women during the transition to and after menopause. The chronic hypo-estrogenic state of menopause may reduce the response to antidepressants; however the influence of estrogen therapy on their efficacy is still controversial. This study aimed at investigating the effects of combining escitalopram with 17β-estradiol on depression and cognitive impairment induced by ovariectomy, an experimental model of human menopause. Young adult female Wistar rats were subjected to either sham operation or ovariectomy. Ovariectomized animals were treated chronically with escitalopram (10mg/kg/day, i.p) alone or with four doses of 17β-estradiol (40μg/kg, s.c) given prior to the behavioral tests. Co-administration of 17β-estradiol improved escitalopram-induced antidepressant effect in forced swimming test verified as more prominent decrease in the immobility time without opposing its memory enhancing effect in Morris water maze. 17β-estradiol augmented the modulatory effects of escitalopram on the hippocampal levels of brain-derived neurotrophic factor and serotonin reuptake transporter as well as tumor necrosis factor-alpha without altering its effects on the gene expressions of serotonin receptor 1A, estrogen receptors alpha and beta, or acetylcholinestearase content. This combined therapy afforded synergistic protective effects on the brain histopathological architecture, particularly, the hippocampus. The antidepressant effect of 17β-estradiol was abolished by pretreatment with estrogen receptor antagonist, tamoxifen (10mg/kg, p.o). In conclusion, 17β-estradiol-induced antidepressant effect was confined to intracellular estrogen receptors activation. Moreover, 17β-estradiol enhanced escitalopram's efficiency in ameliorating menopausal-like depression, via exerting synergistic neuroprotective and serotonin reuptake transporter modulatory effects, without impeding escitalopram-mediated cognitive

Estradiol levels in women predict skin conductance response but not valence and expectancy ratings in conditioned fear extinction.

PubMed

White, Emily C; Graham, Bronwyn M

2016-10-01

Anxiety disorders are more prevalent in women than men. One contributing factor may be the sex hormone estradiol, which is known to impact the long term recall of conditioned fear extinction, a laboratory procedure that forms the basis of exposure therapy for anxiety disorders. To date, the literature examining estradiol and fear extinction in humans has focused primarily on physiological measures of fear, such as skin conductance response (SCR) and fear potentiated startle. This is surprising, given that models of anxiety identify at least three important components: physiological symptoms, cognitive beliefs, and avoidance behavior. To help address this gap, we exposed women with naturally high (n=20) or low estradiol (n=19), women using hormonal contraceptives (n=16), and a male control group (n=18) to a fear extinction task, and measured SCR, US expectancy and CS valence ratings. During extinction recall, low estradiol was associated with greater recovery of SCR, but was not related to US expectancy or CS evaluation. Importantly, women using hormonal contraceptives showed a dissociation between SCR and cognitive beliefs: they exhibited a greater recovery of SCR during extinction recall, yet reported similar US expectancy and CS valence ratings to the other female groups. This divergence underscores the importance of assessing multiple measures of fear when examining the role of estradiol in human fear extinction, especially when considering the potential of estradiol as an enhancement for psychological treatments for anxiety disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Does estradiol have an impact on the dipeptidyl peptidase IV enzyme activity of the Prevotella intermedia group bacteria?

PubMed

Fteita, Dareen; Könönen, Eija; Gürsoy, Mervi; Söderling, Eva; Gürsoy, Ulvi Kahraman

2015-12-01

Initiation and development of pregnancy-associated gingivitis is seemingly related to the microbial shift towards specific gram-negative anaerobes in subgingival biofilms. It is known that Prevotella intermedia sensu lato is able to use estradiol as an alternative source of growth instead of vitamin K. The aim of the present study was to investigate the impact of estradiol on the bacterial dipeptidyl peptidase IV (DPPIV) enzyme activity in vitro as a virulent factor of the Prevotella intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, Prevotella pallens, and Prevotella aurantiaca. In all experiments, 2 strains of each Prevotella species were used. Bacteria were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol and were allowed to build biofilms at an air-solid interface. DPPIV activities of biofilms were measured kinetically during 20 min using a fluorometric assay. The enzyme activity was later related to the amount of protein produced by the same biofilm, reflecting the biofilm mass. Estradiol significantly increased DPPIV activities of the 8 Prevotella strains in a strain- and dose-dependent manner. In conclusion, our in vitro experiments indicate that estradiol regulates the DPPIV enzyme activity of P. intermedia, P. nigrescens, P. pallens, and P. aurantiaca strains differently. Our results may, at least partly, explain the role of estradiol to elicit a virulent state which contributes to the pathogenesis of pregnancy-related gingivitis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hormone replacement with 17β-estradiol plus dihydrotestosterone restores male sexual behavior in rats treated neonatally with clomipramine.

PubMed

Limón-Morales, Ofelia; Soria-Fregozo, Cesar; Arteaga-Silva, Marcela; González, Marisela Hernández; Vázquez-Palacios, Gonzalo; Bonilla-Jaime, Herlinda

2014-11-01

Male sexual behavior (MSB) in rodents, in both its consummatory and motivational components, is regulated by hormones such as testosterone, 17β-estradiol and 5-α-dihydrotestosterone. In experiments, neonatal treatment with clomipramine (CMI; a serotonin reuptake inhibitor) reproduces some of the signs of depression in adult age, including reduced sexual behavior manifested in a lower percentage of subjects that mount, intromit and ejaculate, although their testosterone levels were not altered. However, the effect of this treatment on estrogen levels and the consequences of hormone substitution using 17β-estradiol and 5-α-dihydrotestosterone on the expression of male sexual behavior are still unknown. Therefore, the objective of the present study was to analyze the effect of neonatal treatment with CMI on plasma testosterone and 17β-estradiol levels, and the role of testosterone, 17β-estradiol and 5-α-dihydrotestosterone in altering the consummatory and motivational components of sexual behavior in male rats. To this end, it analyzed the copulatory parameters and sexual incentive motivation (SIM) of rats treated with CMI under two conditions: basal and post-hormone replacements. Neonatal treatment with CMI did not affect plasma testosterone or 17β-estradiol concentrations, but did decrease both the consummatory component and sexual motivation according to the results of the SIM test. These aspects were recovered after administering 17β-estradiol +5-α-dihydrotestosterone, but not testosterone. Copyright © 2014 Elsevier Inc. All rights reserved.

Controlled release of beta-estradiol from PLAGA microparticles: the effect of organic phase solvent on encapsulation and release.

PubMed

Birnbaum, D T; Kosmala, J D; Henthorn, D B; Brannon-Peppas, L

2000-04-03

To determine the effect of the organic solvent used during microparticle preparation on the in vitro release of beta-estradiol, a number of formulations were evaluated in terms of size, shape and drug delivery performance. Biodegradable microparticles of poly(lactide-co-glycolide) were prepared containing beta-estradiol that utilized dichloromethane, ethyl acetate or a mixture of dichloromethane and methanol as the organic phase solvent during the particle preparation. The drug delivery behavior from the microparticles was studied and comparisons were made of their physical properties for different formulations. The varying solubilities of beta-estradiol and poly(lactide-co-glycolide) in the solvents studied resulted in biodegradable microparticles with very different physical characteristics. Microparticles prepared from solid suspensions of beta-estradiol using dichloromethane as the organic phase solvent were similar in appearance to microparticles prepared without drug. Microparticles prepared from dichloromethane/methanol solutions appeared transparent to translucent depending on the initial amount of drug used in the formulation. Microparticles prepared using ethyl acetate appeared to have the most homogeneous encapsulation of beta-estradiol, appearing as solid white spheres regardless of initial drug content. Studies showed that microparticles prepared from either ethyl acetate or a mixture of dichloromethane and methanol gave a more constant release profile of beta-estradiol than particles prepared using dichloromethane alone. For all formulations, an initial burst of release increased with increasing drug loading, regardless of the organic solvent used.

DREAM/calsenilin/KChIP3 modulates strategy selection and estradiol-dependent learning and memory.

PubMed

Tunur, Tumay; Stelly, Claire E; Schrader, Laura Ann

2013-11-18

Downstream regulatory element antagonist modulator (DREAM)/calsenilin(C)/K⁺ channel interacting protein 3 (KChIP3) is a multifunctional Ca²⁺-binding protein highly expressed in the hippocampus that inhibits hippocampus-sensitive memory and synaptic plasticity in male mice. Initial studies in our lab suggested opposing effects of DR/C/K3 expression in female mice. Fluctuating hormones that occur during the estrous cycle may affect these results. In this study, we hypothesized that DR/C/K3 interacts with 17β-estradiol, the primary estrogen produced by the ovaries, to play a role in hippocampus function. We investigated the role of estradiol and DR/C/K3 in learning strategy in ovariectomized (OVX) female mice. OVX WT and DR/C/K3 knockout (KO) mice were given three injections of vehicle (sesame oil) or 17β-estradiol benzoate (0.25 mg in 100 mL sesame oil) 48, 24, and 2 h before training and testing. DR/C/K3 and estradiol had a time-dependent effect on strategy use in the female mice. Male KO mice exhibited enhanced place strategy relative to WT 24 h after pre-exposure. Fear memory formation was significantly reduced in intact female KO mice relative to intact WT mice, and OVX reduced fear memory formation in the WT, but had no effect in the KO mice. Long-term potentiation in hippocampus slices from female mice was enhanced by circulating ovarian hormones in both WT and DR/C/K3 KO mice. Paired-pulse depression was not affected by ovarian hormones but was reduced in DR/C/K3 KO mice. These results provide the first evidence that DR/C/K3 plays a timing-dependent role in estradiol regulation of learning, memory, and plasticity.

Accumulation of PCB congeners in nestling tree swallows (Tachycineta bicolor) on the Hudson River, New York

USGS Publications Warehouse

Echols, Kathy R.; Tillitt, Donald E.; Nichols, John W.; Secord, Anne L.; McCarty, John P.

2004-01-01

Tree swallows (Tachycineta bicolor) were used as a sentinel species to monitor the contamination and bioavailability of polychlorinated biphenyls (PCBs) in the Hudson River watershed. Several tree swallow nest box colonies around and downstream from Hudson Falls, NY, were studied. Tree swallow eggs, adults, and 5-, 10-, and 15-day-old nestlings were collected and analyzed for 103 PCB congeners. Emergent insects collected by net (primarily Odonata) or as a food bolus (primarily Diptera) taken from the mouths of adult tree swallows returning to the nest were analyzed in the same manner. Total PCB concentrations (wet weight) in eggs from two contaminated sites ranged from 9000 to 25 000 ng/g and accumulated to 32 000 and 96 000 ng/g in 15-day-old nestling at two contaminated sites. The congener patterns of PCBs in eggs, nestlings, and adults were compared to those found in emergent insects (Odonata and Diptera) using principal components analysis. The PCB patterns of the biota differed from that of Aroclor technical mixtures. PCB patterns in adult tree swallows were similar to those in eggs, while the patterns in dietary insects were similar to nestling tree swallows. Uptake rate constants were determined for tree swallow nestlings and compared between the two contaminated sites. The estimated PCB congener uptake rate constants were 0.008-0.02 d-1 based on uptake in nestlings until day 15 post-hatch. The rate constants were comparable between the two study areas and may be used to predict nestling contamination at other locations. Our studies confirm the utility of nestling tree swallows to evaluate localized PCB contamination.

The vibrational spectroscopic studies and molecular property analysis of Estradiol, Tamoxifen and their interaction by density functional theory

NASA Astrophysics Data System (ADS)

Borah, Mukunda Madhab; Gomti Devi, Th.

2018-07-01

In the present work Tamoxifen, Estradiol and their interaction are studied using the experimental and theoretical methodologies. The spectral characterization was made by using Raman, FTIR, DFT and VEDA calculation. The optimization of the molecules have been studied using basis set B3LYP/6-31 G(d,p). Complete vibrational assignment of Tamoxifen, Estradiol and Estradiol + Tamoxifen have been attempted and the potential energy distribution and normal mode analysis had also been carried out to determine the contributions of bond oscillators in each normal mode. We have optimized several binding modes of Estradiol and Tamoxifen and taken the lowest energy conformer in our interest. The molecular geometry, HOMO-LUMO energy gap, molecular hardness (η), ionization energy (IE), electron affinity (EA), total energy and dipole moment were analyzed. The observed experimental and the scaled theoretical results were found in good agreement.

17β-estradiol regulates the differentiation of cementoblasts via Notch signaling cascade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, Jing; Zhou, Zeyuan; Huang, Li

Estrogen has been well recognized as a key factor in the homeostasis of bone and periodontal tissue, but the way it regulates the activities of cementoblasts, the cell population maintaining cementum has not been fully understood. In this study, we examined the expression of estrogen receptor in OCCM-30 cells and the effect of 17β-estradiol (E2) on the proliferation and differentiation of OCCM-30 cells. We found that both estrogen receptor α and β were expressed in OCCM-30 cells. E2 exerted no significant influence on the proliferation of OCCM-30 cells, but inhibited the transcription and translation of BSP and Runx2 in the early phase of osteogenicmore » induction except the BSP mRNA. Afterwards in the late phase of osteogenic induction, E2 enhanced the transcription and translation of BSP and Runx2 and promoted the calcium deposition. In addition, the expression level of Notch1, NICD and Hey1 mRNAs responded to exogenous E2 in a pattern similar to that of the osteoblastic markers. DAPT could attenuate the effect of E2 on the expression of osteoblastic markers. These findings indicated that E2 might regulate the differentiation of cementoblasts via Notch signaling. - Highlights: • 17β-estradiol showed no significant effect on the proliferation of cementoblasts. • 17β-estradiol promoted the osteoblastic differentiation of cementoblasts despite of an early transient inhibition. • Notch signaling was regulated by 17β-estradiol and was responsible for mediating the effect of E2 on cementoblasts. • Hey1 might display an opposite expression pattern to Notch signaling in certain circumstances.« less

The antidepressant-like effects of topiramate alone or combined with 17β-estradiol in ovariectomized Wistar rats submitted to the forced swimming test.

PubMed

Molina-Hernández, Miguel; Téllez-Alcántara, N Patricia; Olivera-López, Jorge I; Jaramillo, M Teresa

2014-09-01

There is a significant delay in the clinical response of antidepressant drugs, and antidepressant treatments produce side effects. We examined the relationship between 17β-estradiol and topiramate in ovariectomized Wistar rats submitted to the forced swimming test (FST). Topiramate was administered alone or combined with 17β-estradiol to ovariectomized rats submitted to the FST. Topiramate (20 mg/kg, P < 0.05; 30 mg/kg, P < 0.05) reduced immobility by increasing swimming; these effects were antagonized by finasteride (50 mg/kg). In interaction experiments, topiramate (10 mg/kg) plus 17β-estradiol (5 micrograms per rat; P < 0.05) reduced immobility by increasing swimming behavior. Besides, 17β-estradiol (2.5 micrograms per rat) shortened the onset of the antidepressant-like effects of topiramate (P < 0.05). In the open field test, topiramate alone or combined with 17β-estradiol (P < 0.05) reduced locomotion. Topiramate alone or combined with 17β-estradiol produced antidepressant-like actions; and 17β-estradiol shortened the onset of the antidepressant-like effects of topiramate.

Response to Ecological Risk Assessment Forum Request for Information on the Benefits of PCB Congener-Specific Analyses

EPA Science Inventory

In August, 2001, the Ecological Risk Assessment Forum (ERAF) submitted a formal question to the Ecological Risk Assessment Support Center (ERASC) on the benefits of evaluating PCB congeners in environmental samples. This question was developed by ERAF members Bruce Duncan and Cla...

Treatment of postmenopausal vaginal atrophy with 10-μg estradiol vaginal tablets.

PubMed

Panay, Nick; Maamari, Ricardo

2012-03-01

Postmenopausal estrogen deficiency can lead to symptoms of urogenital atrophy. Individuals with urogenital atrophy have symptoms that include vaginal dryness, vaginal and vulval irritation, vaginal soreness, pain and burning during urination (dysuria), increased vaginal discharge, vaginal odour, vaginal infections, recurrent urinary tract infections, pain associated with sexual activity (dyspareunia) and vaginal bleeding associated with sexual activity. Despite the frequency and effects of vaginal atrophy symptoms, they are often under-reported and, consequently, under-treated. Therefore, care of a menopausal woman should include a physical assessment of vaginal atrophy and a dialogue between the physician and the patient that explores existing symptoms and their effect on vulvovaginal health, sexuality and quality-of-life issues. The development of the ultra-low-dose 10-µg estradiol vaginal tablets is in line with the requirements of regulatory agencies and women's health societies regarding the use of the lowest effective hormonal dose. Because of its effectiveness and safety profiles, in addition to its minimal systemic absorption, the 10-µg estradiol vaginal tablet can offer greater reassurance to health-care providers and postmenopausal women with an annual estradiol administration of only 1.14 mg.

Estradiol is a critical regulator of food-reward behavior.

PubMed

Richard, Jennifer E; López-Ferreras, Lorena; Anderberg, Rozita H; Olandersson, Kajsa; Skibicka, Karolina P

2017-04-01

Food intake is reduced by estrogenic hormones, levels of which vary throughout life and fluctuate throughout the ovarian cycle in females. However, estrogens have also been shown to increase reward derived from drugs of abuse, where motivational properties of drugs and progression to addiction are potentiated by estrogens. Whether reward derived from food, and specifically motivational properties of food, are altered by estrogens remains unknown. Here we investigated the effect of the estrous cycle on food reward behavior and show estrous cycle dictated variability in food motivation, measured by progressive ratio operant conditioning, in female rats. Reward behavior was lowest on days associated with high estrogen signaling. We therefore also examined the actions of subcutaneously administered β-estradiol on food reward and found that β-estradiol reduced food reward behavior. The ventral tegmental area (VTA) is a crucial node of the neurocircuitry underlying motivated behavior and estrogen receptors are expressed in this nucleus. Thus, we examined whether the effects of estrogens on reward were exerted directly at the level of the VTA. Intra-VTA microinjection of β-estradiol led to a significant reduction in food-motivated behavior. Interestingly, this effect was not accompanied by a reduction in chow intake or body weight, nor did it alter locomotor activity. Importantly, removal of the ovaries produced a potent and lasting elevation in food reward and food-seeking behavior, suggesting that ovarian sex steroids are critical for maintenance of normal food reward behavior. These data reveal a novel role for estrogens in the control of food reward behavior.​. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inverse association of highly chlorinated dioxin congeners in maternal breast milk with dehydroepiandrosterone levels in three-year-old Vietnamese children.

PubMed

Kido, Teruhiko; Honma, Seijiro; Nhu, Dang Duc; Manh, Ho Dung; Van Tung, Dao; Liang, Sun Xian; Anh, Le Thai; Okamoto, Rie; Maruzeni, Shoko; Nakagawa, Hideaki; Hung, Nguyen Ngoc; Son, Le Ke

2016-04-15

This study aims to evaluate the endocrine-disrupting effect of dioxin congeners on adrenal steroid hormones in mother-child pairs. In our previous study, we found that cortisol and cortisone levels were higher in the blood and the saliva of mothers living in a dioxin hotspot area than in mothers from a non-exposed region in Vietnam. In this follow-up study, we determined the salivary steroid hormone levels in 49 and 55 three-year-old children of these mothers in the hotspot and non-exposed region, respectively. Steroid hormones were determined by liquid chromatography-tandem mass spectrometry, and dioxin in the maternal breast milk was determined by gas chromatography-mass spectrometry. Dioxin levels in the breast milk of mothers from the hotspot (median total toxic equivalents polychlorinated dibenzodioxins/polychlorinated dibenzofurans; (TEQ PCDD/Fs) of 11pg/g lipid) were three to four times higher than those of mothers in the non-exposed region (median TEQ PCDD/Fs of 3.07pg/g lipid). Salivary dehydroepiandrosterone (DHEA) levels in children were found to be significantly lower in the hotspot than in the non-exposed region, while cortisol and cortisone levels were not different between the two regions. Highly chlorinated dioxin congeners, such as octacholorodibenzodioxin (OCDD), 1,2,3,4,6,7,8-heptacholorodibenzodioxin (HpCDD) and 1,2,3,4 (or 6), 7,8-hexachlorodibenzodioxin Hx(CDD), showed stronger inverse associations with the children's salivary DHEA than other lowly chlorinated dioxin congeners. Glucocorticoid levels in the mothers exhibited a significantly positive correlation with OCDD and HpCDD/F (polychlorinated dibenzofurans). In conclusion, highly chlorinated dioxin congeners are more strongly correlated with endocrine-disrupting effects on adrenal hormones, resulting in high cortisol levels in the mothers and low DHEA levels in their three-year-old children. Copyright © 2016 Elsevier B.V. All rights reserved.

Estradiol and GPER Activation Differentially Affect Cell Proliferation but Not GPER Expression in the Hippocampus of Adult Female Rats

PubMed Central

Duarte-Guterman, Paula; Lieblich, Stephanie E.; Chow, Carmen; Galea, Liisa A. M.

2015-01-01

Estradiol increases cell proliferation in the dentate gyrus of the female rodent but it is not known whether the G protein-coupled estrogen receptor (GPER), a membrane receptor, is involved in this process, nor whether there are regional differences in estradiol’s effects on cell proliferation. Thus, we investigated whether estradiol exerts its effects on cell proliferation in the dorsal and ventral dentate gyrus through GPER, using the GPER agonist, G1, and antagonist, G15. Ovariectomized adult female rats received a single injection of either: 17β-estradiol (10 μg), G1 (0.1, 5, 10 μg), G15 (40 μg), G15 and estradiol, or vehicle (oil, DMSO, or oil+DMSO). After 30 min, animals received an injection of bromodeoxyuridine (BrdU) and were perfused 24 h later. Acute treatment with estradiol increased, while the GPER agonist G1 (5 μg) decreased, the number of BrdU+ cells in the dentate gyrus relative to controls. The GPER antagonist, G15 increased the number of BrdU+ cells relative to control in the dorsal region and decreased the number of BrdU+ cells in the ventral region. However, G15 treatment in conjunction with estradiol partially eliminated the estradiol-induced increase in cell proliferation in the dorsal dentate gyrus. Furthermore, G1 decreased the expression of GPER in the dentate gyrus but not the CA1 and CA3 regions of the hippocampus. In summary, we found that activation of GPER decreased cell proliferation and GPER expression in the dentate gyrus of young female rats, presenting a potential and novel estrogen-independent role for this receptor in the adult hippocampus. PMID:26075609

The association between estradiol levels, hormonal contraceptive use, and responsiveness to one-session-treatment for spider phobia in women.

PubMed

Graham, Bronwyn M; Li, Sophie H; Black, Melissa J; Öst, Lars-Göran

2018-04-01

Preclinical studies have demonstrated that conditioned fear extinction is impaired in females with low endogenous levels of the sex hormone estradiol, due to menstrual fluctuations or hormonal contraceptive use. As fear extinction is a laboratory model of exposure therapy for anxiety and trauma disorders, here we assessed the hypothesis that treatment outcomes may be diminished when exposure therapy occurs during periods of low estradiol. 90 women with spider phobia (60 cycling and 30 using hormonal contraceptives) underwent a one-session exposure treatment for spider phobia, following which, serum estradiol levels were assessed. A median split in estradiol level was used to divide cycling participants into two groups; lower and higher estradiol. Behavioral avoidance and self-reported fear of spiders were measured pre-treatment, post-treatment, and at a 12 week follow-up assessment. Women using hormonal contraceptives exhibited a significantly slower rate of improvement across treatment, greater behavioral avoidance at post-treatment and follow-up, and fewer self-initiated post-treatment exposure tasks, relative to both groups of cycling women, who did not differ. No group differences in self-reported fear were evident. Correlational analyses revealed that across the whole sample, lower estradiol levels were associated with slower rates of improvement across treatment, and greater self-reported fear and behavioral avoidance at post-treatment, but not follow-up. These results provide the first evidence of an association between endogenous estradiol, hormonal contraceptive use, and exposure therapy outcomes in spider phobic women. Hormonal profile may partly account for variability in responsiveness to psychological treatments for anxiety and trauma disorders in women. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bio- and chemical syntheses of mangiferin and congeners.

PubMed

Ehianeta, Teddy Stephen; Laval, Stéphane; Yu, Biao

2016-09-10

Mangiferin (2C-β-d-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone) is a xanthone C-glycoside occurring in many plant species. Composed of a glucose unit C1→2 linked to a 1,3,6,7-tetrahydroxyxanthone aglycone, mangiferin exhibits a wide range of biological activities, which recently renewed its interest as a potential pharmacophore. Mangiferin is mainly isolated after extraction procedures from natural sources alongside with its isoforms isomangiferin, homomangiferin, and neomangiferin. However, enzymatic and chemical approaches have been developed to access these phytochemicals, which address the challenging construction of the C-glycosidic linkage. In addition, both approaches have been exploited to modify the aglycone and the sugar moiety in order to afford analogues with specific and improved pharmacological activities. Herein, we provide a comprehensive review on the biosynthesis and chemical synthesis of mangiferin and its congeners. © 2016 BioFactors, 42(5):445-458, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Bisphenol A and estradiol impede myoblast differentiation through down-regulating Akt signaling pathway.

PubMed

Go, Ga-Yeon; Lee, Sang-Jin; Jo, Ayoung; Lee, Jae-Rin; Kang, Jong-Sun; Yang, Mihi; Bae, Gyu-Un

2018-04-20

Bisphenol A (BPA), one of the most widespread endocrine disrupting chemicals, is known as an artificial estrogen, which interacts with estrogen receptor (ER). In this study, we investigated the effects of BPA and estradiol on myoblast differentiation and the underlying signaling mechanism. Exposure to BPA (0.01-1 μM) in mouse myoblast C2C12 cells attenuated myogenic differentiation via the reduced expression of muscle-specific genes, such as myosin heavy chain (MHC), MyoD, and Myogenin, without the alteration of cell proliferation and viability. BPA-exposed C2C12 myoblasts also showed a reduction of Akt phosphorylation ((37-61) %, p < 0.001), a key event for myogenesis. Similarly to BPA, estradiol (0.01-1 μM) reduced the expression of muscle-specific proteins and the formation of multinucleated myotubes, and attenuated the muscle differentiation-specific phosphorylation of Akt ((42-59) %, p < 0.001). We conclude that BPA and estradiol suppress myogenic differentiation through the inhibition of Akt signaling. Copyright © 2018 Elsevier B.V. All rights reserved.

Fate of estradiol and testosterone in anaerobic lagoon digestors

USDA-ARS?s Scientific Manuscript database

Laboratory-scale lagoon digestors were constructed, and the fate of 14C-labelled 17ß-estradiol (E2) and testosterone (Test) were monitored for 42 d anaerobically under biological and sterile conditions. Hormone levels decreased in the liquid layer and increased in the sludge with time. At 42 d, 16-2...

21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

Code of Federal Regulations, 2014 CFR

2014-04-01

...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... dairy or beef replacement heifers. Safety and effectiveness have not been established in veal calves. A... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Trenbolone acetate and estradiol benzoate. 522.2478 Section 522.2478 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

Code of Federal Regulations, 2013 CFR

2013-04-01

...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... dairy or beef replacement heifers. Safety and effectiveness have not been established in veal calves. A... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Trenbolone acetate and estradiol benzoate. 522.2478 Section 522.2478 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... dairy or beef replacement heifers. Safety and effectiveness have not been established in veal calves. A... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Trenbolone acetate and estradiol benzoate. 522.2478 Section 522.2478 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... dairy or beef replacement heifers. Safety and effectiveness have not been established in veal calves. A... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Trenbolone acetate and estradiol benzoate. 522.2478 Section 522.2478 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

Code of Federal Regulations, 2011 CFR

2011-04-01

...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

Code of Federal Regulations, 2010 CFR

2010-04-01

...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

Code of Federal Regulations, 2012 CFR

2012-04-01

...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... dairy or beef replacement heifers. Safety and effectiveness have not been established in veal calves. A... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Trenbolone acetate and estradiol benzoate. 522.2478 Section 522.2478 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

Marrow Ablative and Immunosuppressive Effects of I-131-anti-CD45 Antibody in Congenic and H2-Mismatched Murine Transplant Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matthews, D. C.; Martin, P J.; Nourigat, C.

1998-12-01

Targeted hematopoietic irradiation delivered by I-131-anti-CD45 antibody has been combined with conventional marrow transplant preparative regimens in an effort to decrease relapse. Before increasing the proportion of therapy delivered by radiolabeled antibody, the myeloablative and immunosuppressive effects of such low dose rate irradiation must be quantitated. We have examined the ability of I-131-anti-CD45 antibody to facilitate engraftment in Ly5-congenic and H2-mismatched murine marrow transplant models. Recipient B6-Ly5-a mice were treated with 30F11 antibody labeled with 0.1 to 1.5 mCi I-131 and/or total body irradiation (TBI), followed by T-cell-depleted marrow from Ly5-b-congenic (C57BL/6) or H2-mismatched (BALB/c) donors. Engraftment was achieved readilymore » in the Ly5-congenic setting, with greater than 80% donor granulocytes and T cells after 0.5 mCi I-131 (estimated 17 Gy to marrow) or 8 Gy TBI. A higher TBI dose (14 Gy) was required to achieve engraftment of H2-mismatched mar row, and engraftment occurred in only 3 of 11 mice receiving 1.5 mCi I-131 delivered by anti-CD45 antibody. Engraftment of H2-mismatched marrow was achieved in 22 of 23 animals receiving 0.75 mCi I-131 delivered by anti-CD45 antibody combined with 8 Gy TBI. Thus, targeted radiation delivered via I-131-anti-CD45 antibody can enable engraftment of congenic marrow and can partially replace TBI when transplanting T-cell-depleted H2-mismatched marrow.« less

Physiological and biochemical effects of 17β estradiol in aging female rat brain.

PubMed

Kumar, Pardeep; Taha, Asia; Kale, R K; Cowsik, S M; Baquer, Najma Zaheer

2011-07-01

Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease. These changes increase during menopausal condition in females when the level of estradiol is decreased. The objective of this study was to observe the changes in activities of monoamine oxidase, glucose transporter-4 levels, membrane fluidity, lipid peroxidation levels and lipofuscin accumulation occurring in brains of female rats of 3 months (young), 12 months (adult) and 24 months (old) age groups, and to see whether these changes are restored to normal levels after exogenous administration of estradiol (0.1 μg/g body weight for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in the brains of aging female rats, and a decrease in glucose transporter-4 level and membrane fluidity. Our data showed that estradiol treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, and a reversal of glucose transporter-4 levels and membrane fluidity was achieved, therefore it can be concluded from the present findings that estradiol's beneficial effects seemed to arise from its antilipofuscin, antioxidant and antilipidperoxidative effects, implying an overall anti-aging action. The results of this study will be useful for pharmacological modification of the aging process and applying new strategies for control of age related disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.

PubMed

Valladares, Macarena; Plaza-Parrochia, Francisca; Lépez, Macarena; López, Daniela; Gabler, Fernando; Gayan, Patricio; Selman, Alberto; Vega, Margarita; Romero, Carmen

2017-11-01

Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERβ), altered ERα/ERβ ratio may constitute a marker of ovarian carcinogenesis progression. To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC). Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERβ and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated. In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERβ levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05). Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.

Cytochrome P450 responses and PCB congeners in pipping heron embryos from Virginia, the Great Lakes and San Francisco Bay

USGS Publications Warehouse

Rattner, B.A.; Melancon, M.J.; Custer, T.W.; Tillett, D.E.; Woodin, Bruce R.; Stegeman, John J.

1992-01-01

Pipping black-crowned night-heron (Nvcticorax nvcticorax) embryos were collected from undisturbed (Chincoteague National Wildlife Refuge VA; CNWR) and industrialized (Cat Island, Green Bay WI and San Francisco Bay, CA; SFB) locations. Hepatic monooxygenases (AHH, EROD, BROD, ECOD) were induced up to 100-fold, and were correlated (r=0.50 to 0.72) with total PCB burdens (N =61 embryos). A subset of 30 embryos have now been analyzed by GC/MS for 12 AHH-active PCB congeners and by Western blot for cytochromes P450lA and P450llB. At Cat Island, concentrations of 8 congeners were greater (P <0.05) than at CNWR. P450lA and P450llB were detected in 44% and 100% of the Cat Island embryos compared to 8% and 33% of the CNWR + SFB embryos. Cytochrome P450 parameters were correlated with the total PCBs (r =0.44 to 0.67) and with at least 9 PCB congeners (r =0.39 to 0.77). Since P450 responses might be affected by other contaminants, sample extract potency in the H411E rat hepatoma bioassay is being determined to study relationships among dioxin equivalents and cytochrome P450 parameters.

Glassy carbon electrode modified with carbon black for sensitive estradiol determination by means of voltammetry and flow injection analysis with amperometric detection.

PubMed

Smajdor, Joanna; Piech, Robert; Ławrywianiec, Martyna; Paczosa-Bator, Beata

2018-03-01

A voltammetric method for fast and sensitive estradiol determination using carbon black modified glassy carbon electrode (CBGC) is proposed. The use of carbon black as a modifying layer led to obtain low detection limit (9.2·10 -8  mol L -1 for a preconcentration time of 60 s) and stability of registered signals (measured as RSD is 1.3%, n = 7, estradiol concentration 0.5·10 -6  mol L -1 ). Cyclic voltammetry study revealed that in phosphate media estradiol suffers irreversible one-proton and one-electron oxidation process. Under the optimum conditions, estradiol calibration curve was linear in the concentration range from 0.15·10 -6 to 3.5·10 -6  mol L -1 . The proposed method enable to determine estradiol content in different pharmaceutical formulation with good recovery. Amperometric measurements of estradiol were performed as well to indicate the possibility of its fast and accurate determination under the flow conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

A novel 17β-hydroxysteroid dehydrogenase in Rhodococcus sp. P14 for transforming 17β-estradiol to estrone.

PubMed

Ye, Xueying; Wang, Hui; Kan, Jie; Li, Jin; Huang, Tongwang; Xiong, Guangming; Hu, Zhong

2017-10-01

17β-hydroxysteroid dehydrogenases (17β-HSD) are a group of oxidoreductase enzymes that exhibit high specificity for 17C reduction/oxidation. However, the mechanism of 17β-HSD in oxidizing steroid hormone 17β-estradiol to estrone in bacterium is still unclear. In this work, a functional bacterium Rhodococcus sp. P14 was identified having rapid ability to oxidize estradiol into estrone in mineral salt medium (MSM) within 6 h. The functional genes encoding NADH-dependent oxidoreductase were successfully detected with the help of bioinformatics, and it was identified that it contained two consensus regions affiliated to the short-chain dehydrogenase/reductase (SDR) superfamily. Expression of 17β-HSD could be induced by estradiol in strain P14. The 17β-HSD gene from Rhodococcus sp. P14 was expressed in Escherichia coli strain BL21. Furthermore, recombinant 17β-HSD-expressing BL21 cells showed a high transformation rate, they are capable of transforming estradiol to estrone up to 94%. The purified His-17β-HSD protein also exhibited high catalyzing efficiency. In conclusion, this study provides the first evidence that a novel 17β-HSD in Rhodococcus sp. P14 can catalyze the oxidation of estradiol. Copyright © 2017 Elsevier B.V. All rights reserved.

Naproxen or estradiol for bleeding and spotting with the levonorgestrel intrauterine system: a randomized controlled trial.

PubMed

Madden, Tessa; Proehl, Sarah; Allsworth, Jenifer E; Secura, Gina M; Peipert, Jeffrey F

2012-02-01

The purpose of this study was to evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women who are initiating the levonorgestrel-releasing intrauterine system. We conducted a randomized controlled trial of naproxen, estradiol, or placebo that was administered over the first 12 weeks of levonorgestrel-releasing intrauterine system use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis. There were 129 women who were assigned randomly to naproxen (n = 42 women), estradiol (n = 44 women), or placebo (n = 43 women). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared with placebo (42.9% vs 16.3%; P = .03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (adjusted relative risk, 0.90; 95% confidence interval, 0.84-0.97) compared with placebo. More frequent bleeding and spotting was observed in the estradiol group (adjusted relative risk, 1.25; 95% confidence interval, 1.17-1.34). The administration of naproxen resulted in a reduction in bleeding and spotting days compared with placebo. Copyright © 2012 Mosby, Inc. All rights reserved.

Effects of estradiol on learned helplessness and associated remodeling of hippocampal spine synapses in female rats.

PubMed

Hajszan, Tibor; Szigeti-Buck, Klara; Sallam, Nermin L; Bober, Jeremy; Parducz, Arpad; Maclusky, Neil J; Leranth, Csaba; Duman, Ronald S

2010-01-15

Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in female subjects is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant desipramine. Considering that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life might influence behavioral and synaptic responses to stress and depression. With electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n = 70), under different conditions of estradiol exposure. Stress induced an acute and persistent loss of hippocampal spine synapses, whereas subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either before stress or before escape testing of nonstressed animals increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. These findings suggest that hippocampal spine synapse remodeling might be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression.

Estradiol and Metabolic Syndrome in Older Italian Men: the InCHIANTI Study

PubMed Central

Maggio, Marcello; Lauretani, Fulvio; Ceda, Gian Paolo; Bandinelli, Stefania; Basaria, Shehzad; Paolisso, Giuseppe; Giumelli, Claudio; Luci, Michele; Najjar, Samer S.; Metter, E. Jeffrey; Valenti, Giorgio; Guralnik, Jack; Ferrucci, Luigi

2009-01-01

The increasing prevalence of metabolic syndrome (MS) with age in older men has been linked with decreasing testosterone levels. Interestingly, while testosterone levels decline with age, estradiol (E2) levels remain relatively stable resulting in a decreased testosterone/estradiol ratio. Because E2 levels tend to be elevated in morbid obesity, insulin resistance and diabetes, it is reasonable to hypothesize that high E2 levels are associated with MS in older men. We studied the relationship of total and free E2 with MS after adjustment for multiple confounders including age, BMI, smoking, alcohol consumption, physical activity, interleukin-6 (IL-6), fasting insulin and testosterone. 452 men 65 yr or older (age range 65–96) had complete data on estradiol, testosterone, fasting insulin, sex hormone binding globulin, interleukin-6 (IL-6), and albumin. Concentrations of free estradiol and free testosterone were calculated using the mass action equations. MS was defined according to ATPIII criteria. Participants with MS had significantly higher serum free and total E2 (p<.001) (p=0.003). After adjusting for confounders, including age, smoking, alcohol consumption, physical activity, log (IL-6), log (insulin), participants with higher log (total E2) (OR: 2.31, 95 % CI 1.39–4.70, p=0.02) and higher log (free E2) (OR: 2.69, 1.38–5.24, p<0.001) had an increased risk of having MS. Log (free E2) (p=0.04) maintained significant correlation with MS even after further adjustment for BMI. In older men high E2 is independently associated with MS. Whether confirmed in other studies, assessment of E2 should be also considered in older men. Whether changes in this hormonal pattern play a role in the development of MS should be further tested in longitudinal studies. PMID:19059904

Early Postmenopausal Transdermal 17β-Estradiol Therapy and Amyloid-β Deposition.

PubMed

Kantarci, Kejal; Lowe, Val J; Lesnick, Timothy G; Tosakulwong, Nirubol; Bailey, Kent R; Fields, Julie A; Shuster, Lynne T; Zuk, Samantha M; Senjem, Matthew L; Mielke, Michelle M; Gleason, Carey; Jack, Clifford R; Rocca, Walter A; Miller, Virginia M

2016-05-07

It remains controversial whether hormone therapy in recently postmenopausal women modifies the risk of Alzheimer's disease (AD). To investigate the effects of hormone therapy on amyloid-β deposition in recently postmenopausal women. Participants within 5-36 months past menopause in the Kronos Early Estrogen Prevention Study, a randomized, double blinded placebo-controlled clinical trial, were randomized to: 1) 0.45 mg/day oral conjugated equine estrogens (CEE); 2) 50μg/day transdermal 17β-estradiol; or 3) placebo pills and patch for four years. Oral progesterone (200 mg/day) was given to active treatment groups for 12 days each month. 11C Pittsburgh compound B (PiB) PET imaging was performed in 68 of the 118 participants at Mayo Clinic approximately seven years post randomization and three years after stopping randomized treatment. PiB Standard unit value ratio (SUVR) was calculated. Women (age = 52-65) randomized to transdermal 17β-estradiol (n = 21) had lower PiB SUVR compared to placebo (n = 30) after adjusting for age [odds ratio (95% CI) = 0.31(0.11-0.83)]. In the APOEɛ4 carriers, transdermal 17β-estradiol treated women (n = 10) had lower PiB SUVR compared to either placebo (n = 5) [odds ratio (95% CI) = 0.04(0.004-0.44)], or the oral CEE treated group (n = 3) [odds ratio (95% CI) = 0.01(0.0006-0.23)] after adjusting for age. Hormone therapy was not associated with PiB SUVR in the APOEɛ4 non-carriers. In this pilot study, transdermal 17β-estradiol therapy in recently postmenopausal women was associated with a reduced amyloid-β deposition, particularly in APOEɛ4 carriers. This finding may have important implications for the prevention of AD in postmenopausal women, and needs to be confirmed in a larger sample.

Progesterone After Estradiol Modulates Shuttle-Cage Escape by Facilitating Volition

PubMed Central

Mayeaux, Darryl J.; Tandle, Sarah M.; Cilano, Sean M.; Fitzharris, Matthew J.

2015-01-01

In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized female rats to examine their performance in shuttle-cage escape learning without intentionally inducing a depressive-like state. Progesterone, not estradiol, within four hours of testing affected latencies to escape. The improvement produced by progesterone was in the decision to act, not in the speed of learning or speed of escaping. This parallels depression in humans in that depressed people are slower in volition, in their decisions to take action. PMID:26823653

Progesterone and estradiol profiles in different reproductive stages of captive collared peccary (Pecari tajacu) females assessed by fecal metabolites.

PubMed

Ahuja-Aguirre, Concepción; López-deBuen, Lorena; Rojas-Maya, Susana; Hernández-Cruz, Bertha C

2017-05-01

The study determined the fecal progesterone and estradiol profiles in different reproductive stages of captive collared peccary (Pecari tajacu) females from eastern Mexico. Fifteen adult females were included. At the start of the study the females were either pregnant (early, mid, or late pregnancy), lactating, or non-lactating of unknown pregnancy status. Feces from each female were collected once a week during nine consecutive months to determine concentrations of fecal progesterone and estradiol metabolites using ELISA. Progesterone was similar in early (2048±285ng/g), mid (2254±274ng/g), and late pregnancy (2491±374ng/g), and in early-pregnant and non-lactating females (1154±274ng/g). Progesterone in lactating females (442±255ng/g) was lower than in females at any stage of pregnancy, but was similar to non-lactating females. Overall progesterone in pregnant females (2229±173ng/g) was higher than in lactating and non-lactating females together (772±189ng/g). Estradiol was similar in early (66±8ng/g), mid (83±9ng/g), late pregnant (109±15ng/g), and non-lactating females (64±9ng/g). Estradiol in lactating females (34±8ng/g) was similar to estradiol in early-pregnant and non-lactating females, but was lower than in females in late and mid pregnancy. Overall estradiol in pregnant females (79±6ng/g) was similar to non-lactating females, but higher than in lactating females. The progesterone and estradiol profiles of captive collared peccary females at different reproductive stages were determined by assessing concentrations of fecal hormone metabolites. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis of (+)-dumetorine and congeners by using flow chemistry technologies.

PubMed

Riva, Elena; Rencurosi, Anna; Gagliardi, Stefania; Passarella, Daniele; Martinelli, Marisa

2011-05-23

An efficient total synthesis of the natural alkaloid (+)-dumetorine by using flow technology is described. The process entailed five separate steps starting from the enantiopure (S)-2-(piperidin-2-yl)ethanol 4 with 29% overall yield. Most of the reactions were carried out by exploiting solvent superheating and by using packed columns of immobilized reagents or scavengers to minimize handling. New protocols for performing classical reactions under continuous flow are disclosed: the ring-closing metathesis reaction with a novel polyethylene glycol-supported Hoveyda catalyst and the unprecedented flow deprotection/Eschweiler-Clarke methylation sequence. The new protocols developed for the synthesis of (+)-dumetorine were applied to the synthesis of its simplified natural congeners (-)-sedamine and (+)-sedridine. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Association of circulating concentrations of estradiol during the preovulatory period and expression of steroidogenic enzymes in beef cows

USDA-ARS?s Scientific Manuscript database

Cows with greater circulating concentrations of estradiol during the preovulatory period (HighE2) have increased pregnancy success following a fixed-time AI protocol. Furthermore, these animals have an enhanced ability to produce estradiol as indicated by increased expression of CYP19A1 and LHR wit...

Effect of estradiol on planktonic growth, coaggregation, and biofilm formation of the Prevotella intermedia group bacteria.

PubMed

Fteita, Dareen; Könönen, Eija; Söderling, Eva; Gürsoy, Ulvi Kahraman

2014-06-01

Alterations in the quantity and quality of biofilms at gingival margin are considered to play a role in the initiation and development of pregnancy-related gingivitis. Prevotella intermedia sensu lato is able to consume estradiol, the major sex hormone secreted during pregnancy, in the absence of vitamin K. The aim of the study was to examine the effect of estradiol on the planktonic growth, coaggregation, polysaccharide production, and biofilm formation of the P. intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, and Prevotella pallens. In all experiments, the type strain (ATCC) and a clinical strain (AHN) of P. intermedia, P. nigrescens, and P. pallens were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol. Planktonic growth was assessed by means of the colony forming unit method, while coaggregation and biofilm formation were assessed by spectrophotometric methods. In the determination of protein and polysaccharide levels, the Bradford and phenol-sulfuric acid methods were used, respectively. P. pallens AHN 9283 and P. nigrescens ATCC 33563 increased their numbers at planktonic stage with increasing estradiol concentrations. In 48-h biofilm tests, elevated protein levels were found for both strains of P. intermedia, and the strains P. nigrescens ATCC 33563 and P. pallens AHN 9283 in the presence of estradiol. The P. intermedia strains also increased the levels of polysaccharide formation in the biofilm. Coaggregation of the P. intermedia group organisms with Fusobacterium nucleatum was enhanced only in P. intermedia AHN 8290. In conclusion, our in vitro experiments indicate that estradiol regulates planktonic growth, coaggregation, polysaccharide production, and biofilm formation characteristics of P. intermedia, P. nigrescens, and P. pallens differently. These results may, at least partly, explain the differences seen in their contribution to the pathogenesis of pregnancy-related gingivitis

Estradiol coupling to human monocyte nitric oxide release is dependent on intracellular calcium transients: evidence for an estrogen surface receptor.

PubMed

Stefano, G B; Prevot, V; Beauvillain, J C; Fimiani, C; Welters, I; Cadet, P; Breton, C; Pestel, J; Salzet, M; Bilfinger, T V

1999-10-01

We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase (cNOS) activity in human peripheral monocytes by acting on an estrogen surface receptor. NO release was measured in real time with an amperometric probe. 17beta-estradiol exposure to monocytes stimulated NO release within seconds in a concentration-dependent manner, whereas 17alpha-estradiol had no effect. 17beta-estradiol conjugated to BSA (E2-BSA) also stimulated NO release, suggesting mediation by a membrane surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized the action of both 17beta-estradiol and E2-BSA, whereas ICI 182,780, a selective inhibitor of the nuclear estrogen receptor, had no effect. We further showed, using a dual emission microfluorometry in a calcium-free medium, that the 17beta-estradiol-stimulated release of monocyte NO was dependent on the initial stimulation of intracellular calcium transients in a tamoxifen-sensitive process. Leeching out the intracellular calcium stores abolished the effect of 17beta-estradiol on NO release. RT-PCR analysis of RNA obtained from the cells revealed a strong estrogen receptor-alpha amplification signal and a weak beta signal. Taken together, a physiological dose of estrogen acutely stimulates NO release from human monocytes via the activation of an estrogen surface receptor that is coupled to increases in intracellular calcium.

Topological analysis of metabolic networks integrating co-segregating transcriptomes and metabolomes in type 2 diabetic rat congenic series.

PubMed

Dumas, Marc-Emmanuel; Domange, Céline; Calderari, Sophie; Martínez, Andrea Rodríguez; Ayala, Rafael; Wilder, Steven P; Suárez-Zamorano, Nicolas; Collins, Stephan C; Wallis, Robert H; Gu, Quan; Wang, Yulan; Hue, Christophe; Otto, Georg W; Argoud, Karène; Navratil, Vincent; Mitchell, Steve C; Lindon, John C; Holmes, Elaine; Cazier, Jean-Baptiste; Nicholson, Jeremy K; Gauguier, Dominique

2016-09-30

The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus occurs through complex organ-specific cellular mechanisms and networks contributing to impaired insulin secretion and insulin resistance. Genome-wide gene expression profiling systems can dissect the genetic contributions to metabolome and transcriptome regulations. The integrative analysis of multiple gene expression traits and metabolic phenotypes (i.e., metabotypes) together with their underlying genetic regulation remains a challenge. Here, we introduce a systems genetics approach based on the topological analysis of a combined molecular network made of genes and metabolites identified through expression and metabotype quantitative trait locus mapping (i.e., eQTL and mQTL) to prioritise biological characterisation of candidate genes and traits. We used systematic metabotyping by 1 H NMR spectroscopy and genome-wide gene expression in white adipose tissue to map molecular phenotypes to genomic blocks associated with obesity and insulin secretion in a series of rat congenic strains derived from spontaneously diabetic Goto-Kakizaki (GK) and normoglycemic Brown-Norway (BN) rats. We implemented a network biology strategy approach to visualize the shortest paths between metabolites and genes significantly associated with each genomic block. Despite strong genomic similarities (95-99 %) among congenics, each strain exhibited specific patterns of gene expression and metabotypes, reflecting the metabolic consequences of series of linked genetic polymorphisms in the congenic intervals. We subsequently used the congenic panel to map quantitative trait loci underlying specific mQTLs and genome-wide eQTLs. Variation in key metabolites like glucose, succinate, lactate, or 3-hydroxybutyrate and second messenger precursors like inositol was associated with several independent genomic intervals, indicating functional redundancy in these regions. To navigate through the complexity of

Differential accumulation of polychlorinated biphenyl congeners in the terrestrial food web of the Kalamazoo River Superfund site, Michigan.

PubMed

Blankenship, Alan L; Zwiernik, Matthew J; Coady, Katherine K; Kay, Denise P; Newsted, John L; Strause, Karl; Park, Cyrus; Bradley, Patrick W; Neigh, Arianne M; Millsap, Stephanie D; Jones, Paul D; Giesy, John P

2005-08-15

A series of field studies was conducted to determine the bioaccumulation of polychlorinated biphenyl (PCB) congeners in the terrestrial food web of the Kalamazoo River flood plain. Samples included colocated soils, native plants likely to be consumed by wildlife, several taxa of terrestrial invertebrates, small mammals, passerine bird eggs, nestlings, and adults, and great horned owl plasma and eggs. Mean concentrations of total PCBs in samples from the former Trowbridge impoundment were 6.5 mg/kg dry weight for soils and 0.023, 0.13, 1.3, 1.3, 1.6, and 8.2 mg/kg wet weight for plants, small herbivorous mammals, depurated earthworms, shrews, great horned owl eggs, and house wren eggs, respectively. Historical data from the Kalamazoo River have reported Aroclor-equivalent total PCB concentrations in the terrestrial food web; however, the degree of environmental weathering of the parent PCB mixtures was unknown. In this study, earthworms and composite samples of coleoptera exhibited PCB congener patterns that were similar to patterns in colocated soils. However, in plants, less chlorinated PCBs (e.g., mono-, di-, tri-, and tetrachlorinated biphenyls) were predominant, and in small mammals, there was a notable enrichment of PCBs 153, 180, 138, 118, and 99. In general, concentrations of PCBs were lower in most biota than in soil from the Kalamazoo River Area of Concern (KRAOC) although there was a modest biomagnification of PCBs from lower trophic level biota to highertrophic levels. As a consequence of environmental weathering of PCBs in the terrestrial food web of the KRAOC, the relative potency of the PCBs (expressed as mg TEQs/kg PCBs) decreased from soil to most biota. While there was a general trend, as expected, in which concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) increased with total PCBs, this relationship was rather poor (R2 = 0.13). Taken together, these data suggest that the differential accumulation of PCB congeners in the

Mucosal-associated invariant T cell-rich congenic mouse strain allows functional evaluation.

PubMed

Cui, Yue; Franciszkiewicz, Katarzyna; Mburu, Yvonne K; Mondot, Stanislas; Le Bourhis, Lionel; Premel, Virginie; Martin, Emmanuel; Kachaner, Alexandra; Duban, Livine; Ingersoll, Molly A; Rabot, Sylvie; Jaubert, Jean; De Villartay, Jean-Pierre; Soudais, Claire; Lantz, Olivier

2015-11-02

Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%-10% in blood). Despite strong evolutionary conservation of the invariant TCR-α chain and restricting molecule MR1, this population is rare in laboratory mouse strains (≈0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-α locus and led to higher usage of the distal Vα segments, including Vα19. We generated a MAIThi congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory (CD44+) CD4-CD8lo/neg T cells with tissue-homing properties (CCR6+CCR7-). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18Rα, and IL-12Rβ and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptor γ (RORγt). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the MAIThi congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease.

Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years.

PubMed

Kocarnik, Beverly M; Boyko, Edward J; Matsumoto, Alvin M; Fujimoto, Wilfred Y; Hayashi, Tomoshige; Leonetti, Donna L; Page, Stephanie T

The role of plasma estradiol in the accumulation of intra-abdominal fat (IAF) in men is uncertain. Cross-sectional studies using imaging of IAF have shown either a positive or no association. In contrast, a randomised controlled trial using an aromatase inhibitor to suppress estradiol production found an association between oestrogen deficiency and short-term IAF accumulation. No longitudinal study has been conducted to examine the relationship between plasma estradiol concentration and the change in IAF area measured using direct imaging. This is a longitudinal observational study in community-dwelling Japanese-American men (n=215, mean age 52 years, BMI 25.4kg/m 2 ). IAF and subcutaneous fat areas were assessed using computerized tomography (CT) at baseline, 5 and 10 years. Baseline plasma estradiol concentrations were measured using liquid chromatography-tandem mass spectrometry. Univariate analysis found no association between baseline estradiol concentration and baseline IAF, or 5- or 10-year changes in IAF area (r=-0.05 for both time points, p=0.45 and p=0.43, respectively). Multivariate linear regression analysis of the change in IAF area by baseline estradiol concentration adjusted for age, baseline IAF area, and weight change found no association with either the 5- or 10-year IAF area change (p=0.52 and p=0.55, respectively). Plasma estradiol concentration was not associated with baseline IAF nor with change in IAF area over 5 or 10 years based on serial CT scans in community-dwelling Japanese-American men. These results do not support a role for oestrogen deficiency in IAF accumulation in men. Copyright © 2015 Asia Oceania Association for the Study of Obesity. All rights reserved.

Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years

PubMed Central

Kocarnik, Beverly M.; Boyko, Edward J.; Matsumoto, Alvin M.; Fujimoto, Wilfred Y.; Hayashi, Tomoshige; Leonetti, Donna L.; Page, Stephanie T.

2016-01-01

Summary Problem The role of plasma estradiol in the accumulation of intra-abdominal fat (IAF) in men is uncertain. Cross-sectional studies using imaging of IAF have shown either a positive or no association. In contrast, a randomised controlled trial using an aromatase inhibitor to suppress estradiol production found an association between oestrogen deficiency and short-term IAF accumulation. No longitudinal study has been conducted to examine the relationship between plasma estradiol concentration and the change in IAF area measured using direct imaging. Methods This is a longitudinal observational study in community-dwelling Japanese-American men (n = 215, mean age 52 years, BMI 25.4 kg/m2). IAF and subcutaneous fat areas were assessed using computerized tomography (CT) at baseline, 5 and 10 years. Baseline plasma estradiol concentrations were measured using liquid chromatography-tandem mass spectrometry. Results Univariate analysis found no association between baseline estradiol concentration and baseline IAF, or 5- or 10-year changes in IAF area (r = −0.05 for both time points, p = 0.45 and p = 0.43, respectively). Multivariate linear regression analysis of the change in IAF area by baseline estradiol concentration adjusted for age, baseline IAF area, and weight change found no association with either the 5- or 10-year IAF area change (p = 0.52 and p = 0.55, respectively). Conclusions Plasma estradiol concentration was not associated with baseline IAF nor with change in IAF area over 5 or 10 years based on serial CT scans in community-dwelling Japanese-American men. These results do not support a role for oestrogen deficiency in IAF accumulation in men. PMID:26747209

Individual Polychlorinated Biphenyl (PCB) Congeners Produce Tissue- and Gene-Specific Effects on Thyroid Hormone Signaling during Development

PubMed Central

Giera, Stefanie; Bansal, Ruby; Ortiz-Toro, Theresa M.; Taub, Daniel G.

2011-01-01

Polychlorinated biphenyls (PCB) are industrial chemicals linked to developmental deficits that may be caused in part by disrupting thyroid hormone (TH) action by either reducing serum TH or interacting directly with the TH receptor (TR). Individual PCB congeners can activate the TR in vitro when the metabolic enzyme cytochrome P4501A1 (CYP1A1) is induced, suggesting that specific PCB metabolites act as TR agonists. To test this hypothesis in vivo, we compared two combinations of PCB congeners that either activate the TR (PCB 105 and 118) or not (PCB 138 and 153) in the presence or absence of a PCB congener (PCB 126) that induces CYP1A1 in vitro. Aroclor 1254 was used as a positive control, and a group treated with propylthiouracil was included to characterize the effects of low serum TH. We monitored the effects on TH signaling in several peripheral tissues by measuring the mRNA expression of well-known TH-response genes in these tissues. Aroclor 1254 and its component PCB 105/118/126 reduced total T4 to the same extent as that of propylthiouracil but increased the expression of some TH target genes in liver. This effect was strongly correlated with CYP1A1 expression supporting the hypothesis that metabolism is necessary. Effects were gene and tissue specific, indicating that tissue-specific metabolism is an important component of PCB disruption of TH action and that PCB metabolites interact in complex ways with the TR. These are essential mechanisms to consider when evaluating the health risks of contaminant exposures, for both PCB and other polycyclic compounds known to interact with nuclear hormone receptors. PMID:21540284

Simultaneous measurement of total estradiol and testosterone in human serum by isotope dilution liquid chromatography tandem mass spectrometry.

PubMed

Zhou, Hui; Wang, Yuesong; Gatcombe, Matthew; Farris, Jacob; Botelho, Julianne C; Caudill, Samuel P; Vesper, Hubert W

2017-10-01

Reliable measurement of total testosterone and estradiol is critical for their use as biomarkers of hormone-related disorders in patient care and translational research. We developed and validated a mass spectrometry method to simultaneously quantify these analytes in human serum without chemical derivatization. Serum is equilibrated with isotopic internal standards and treated with acidic buffer to release hormones from their binding proteins. Lipids are isolated and polar impurities are removed by two serial liquid-liquid extraction steps. Total testosterone and estradiol are measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) in combination of positive and negative electrospray ionization modes. The method shows broad analytical measurement range for both testosterone 0.03-48.5 nM (0.75-1400 ng/dL) and estradiol 11.0-5138 pM (2.99-1400 pg/mL) and excellent agreement with certified reference materials (mean bias less than 2.1% to SRM 971, BCR 576, 577, and 578) and a high order reference method (mean bias 1.25% for testosterone and -0.84% for estradiol). The high accuracy of the method was monitored and certified by CDC Hormone Standardization (HoSt) Program for 2 years with mean bias -0.7% (95% CI -1.6% to 0.2%) for testosterone and 0.1% (95% CI -2.2% to 2.3%) for estradiol. The method precision over a 2-year period for quality control pools at low, medium, and high concentrations was 2.7-2.9% for testosterone and 3.3-5.3% for estradiol. With the consistently excellent accuracy and precision, this method is readily applicable for high-throughput clinical and epidemiological studies.

TISSUE DISTRIBUTION OF PCBS AND ORGANOCHLORINE PESTICIDES IN ALASKAN NORTHERN FUR SEALS: COMPARISON OF VARIOUS CONGENER CLASSIFICATION SCHEMES

USDA-ARS?s Scientific Manuscript database

Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are believed to adversely affect reproduction and cause health problems in Pinnipeds 1-4. In this study, 145 PCB congeners and OCPs were analyzed in 10 juvenile male northern fur seals, Callorhinus ursinus, collected from Alaskan...

Specific leaf area relates to the differences in leaf construction cost, photosynthesis, nitrogen allocation, and use efficiencies between invasive and noninvasive alien congeners.

PubMed

Feng, Yu-Long; Fu, Gai-Lan; Zheng, Yu-Long

2008-08-01

Comparisons between invasive and native species may not characterize the traits of invasive species, as native species might be invasive elsewhere if they were introduced. In this study, invasive Oxalis corymbosa and Peperomia pellucida were compared with their respective noninvasive alien congeners. We hypothesized that the invasive species have higher specific leaf (SLA) than their respective noninvasive alien congeners, and analyzed the physiological and ecological consequences of the higher SLA. Higher SLA was indeed the most important trait for the two invaders, which was associated with their lower leaf construction cost, higher nitrogen (N) allocation to photosynthesis and photosynthetic N use efficiency (PNUE). The higher N allocation to photosynthesis of the invaders in turn increased their PNUE, N content in photosynthesis, biochemical capacity for photosynthesis, and therefore light-saturated photosynthetic rate. The above resource capture-, use- and growth-related traits may facilitate the two invaders' invasion, while further comparative studies on a wider range of invasive and noninvasive congeners are needed to understand the generality of this pattern and to fully assess the competitive advantages afforded by these traits.

Estradiol increases the expression of TNF-α and TNF receptor 1 in lactotropes.

PubMed

Zaldivar, Verónica; Magri, María Laura; Zárate, Sandra; Jaita, Gabriela; Eijo, Guadalupe; Radl, Daniela; Ferraris, Jimena; Pisera, Daniel; Seilicovich, Adriana

2011-01-01

Estrogens are recognized modulators of pituitary cell renewal, sensitizing cells to mitogenic and apoptotic signals. Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that plays an important role in tissue homeostasis modulating cell proliferation, differentiation and death. We previously demonstrated that TNF-α-induced apoptosis of anterior pituitary cells from female rats is estrogen-dependent and predominant in cells from rats at proestrus when estradiol levels are the highest. Considering that one of the mechanisms involved in the apoptotic action of estrogens can result from increased expression of cytokines and/or their receptors, the aim of the present study was to evaluate the effect of estrogens on the expression of TNF-α and its receptor, TNF receptor 1 (TNFR1), in anterior pituitary cells. TNFR1 expression, determined by Western blot, was higher in anterior pituitary glands from rats at proestrus than at diestrus. Incubation of anterior pituitary cells from ovariectomized rats with 17β-estradiol enhanced TNFR1 protein expression. As determined by double immunocytochemistry, the expression of TNF-α and TNFR1 was detected in prolactin-, GH-, LH- and ACTH-bearing cells. 17β-estradiol increased the percentage of TNF-α and TNFR1-immunoreactive lactotropes but did not modify the number of GH-bearing cells expressing TNF-α or TNFR1. Our results demonstrate that estradiol increases the expression of TNF-α and TNFR1 in anterior pituitary cells, especially in lactotropes. The sensitizing action of estrogens to proapoptotic stimuli at proestrus in the anterior pituitary gland may involve changes in the expression of the TNF-α/TNFR1 system. Copyright © 2011 S. Karger AG, Basel.

The effects of preovulatory estradiol on the uterine environment and conceptus survival from fertilization to maternal recognition of pregnancy

USDA-ARS?s Scientific Manuscript database

Preovulatory estradiol is known to impact embryo quality and survival. The objective of this study is to determine the effects of preovulatory estradiol on the uterine environment and conceptus survival through maternal recognition of pregnancy. Beef cows/heifers were synchronized and artificially...

Segregation of a QTL cluster for home-cage activity using a new mapping method based on regression analysis of congenic mouse strains

PubMed Central

Kato, S; Ishii, A; Nishi, A; Kuriki, S; Koide, T

2014-01-01

Recent genetic studies have shown that genetic loci with significant effects in whole-genome quantitative trait loci (QTL) analyses were lost or weakened in congenic strains. Characterisation of the genetic basis of this attenuated QTL effect is important to our understanding of the genetic mechanisms of complex traits. We previously found that a consomic strain, B6-Chr6CMSM, which carries chromosome 6 of a wild-derived strain MSM/Ms on the genetic background of C57BL/6J, exhibited lower home-cage activity than C57BL/6J. In the present study, we conducted a composite interval QTL analysis using the F2 mice derived from a cross between C57BL/6J and B6-Chr6CMSM. We found one QTL peak that spans 17.6 Mbp of chromosome 6. A subconsomic strain that covers the entire QTL region also showed lower home-cage activity at the same level as the consomic strain. We developed 15 congenic strains, each of which carries a shorter MSM/Ms-derived chromosomal segment from the subconsomic strain. Given that the results of home-cage activity tests on the congenic strains cannot be explained by a simple single-gene model, we applied regression analysis to segregate the multiple genetic loci. The results revealed three loci (loci 1–3) that have the effect of reducing home-cage activity and one locus (locus 4) that increases activity. We also found that the combination of loci 3 and 4 cancels out the effects of the congenic strains, which indicates the existence of a genetic mechanism related to the loss of QTLs. PMID:24781804

Identification of Stmm3 locus Conferring Resistance to Late-stage Chemically Induced Skin Papillomas on Mouse Chromosome 4 by Congenic Mappingand Allele-specific Alteration Analysis

PubMed Central

Saito, Megumi; Okumura, Kazuhiro; Miura, Ikuo; Wakana, Shigeharu; Kominami, Ryo; Wakabayashi, Yuichi

2014-01-01

Genome-wide association studies have revealed that many low-penetrance cancer susceptibility loci are located throughout the genome; however, a very limited number of genes have been identified so far. Using a forward genetics approach to map such loci in a mouse skin cancer model, we previously identified strong genetic loci conferring resistance to chemically induced skin papillomas on chromosome 4 and 7 with a large number of [(FVB/N × MSM/Ms) F1 × FVB/N] backcross mice. In this report, we describe a combination of congenic mapping and allele-specific alteration analysis of the loci on chromosome 4. We used linkage analysis and a congenic mouse strain, FVB.MSM-Stmm3 to refine the location of Stmm3 (Skin tumor modifier of MSM 3) locus within a physical interval of about 34 Mb on distal chromosome 4. In addition, we used patterns of allele-specific imbalances in tumors from N2 and N10 congenic mice to narrow down further the region of Stmm3 locus to a physical distance of about 25 Mb. Furthermore, immunohistochemical analysis showed papillomas from congenic mice had less proliferative activity. These results suggest that Stmm3 responsible genes may have an influence on papilloma formation in the two-stage skin carcinogenesis by regulating papilloma growth rather than development. PMID:25077764

Bioenergetics-based modeling of individual PCB congeners in nestling tree swallows from two contaminated sites on the Upper Hudson River, New York

USGS Publications Warehouse

Nichols, John W.; Echols, Kathy R.; Tillitt, Donald E.; Secord, Anne L.; McCarty, John P.

2004-01-01

A bioenergetics-based model was used to simulate the accumulation of total PCBs and 20 PCB congeners by nestling tree swallows at two contaminated sites on the Upper Hudson River, New York. PCB concentrations in birds were calculated as the sum of inherited residues and those acquired through consumption of contaminated insects. Close agreement between simulations and measured residues in 5-, 10-, and 15-day-old nestlings was obtained when PCB concentrations in the diet were set equal to those in food boli taken from adult birds. These simulations were further optimized by fitting the value of a dietary assimilation efficiency constant. Fitted constants for both sites were similar and averaged about 0.7. An evaluation of model performance for individual congeners provided no evidence of metabolic biotransformation. The results of this study are consistent with a companion effort in which principal components analysis was used to compare PCB congener patterns in insects and in tree swallow eggs, nestlings, and adults. Together, these studies establish a quantitative linkage between nestling tree swallows and the insects that they consume and provide strong support for the use of nestling swallows as a biomonitoring species for exposure assessment.

Dahl (S x R) congenic strain analysis confirms and defines a chromosome 5 female-specific blood pressure quantitative trait locus to <7 Mbp.

PubMed

Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

2012-01-01

The detection of multiple sex-specific blood pressure (BP) quantitative trait loci (QTLs) in independent total genome analyses of F2 (Dahl S x R)-intercross male and female rat cohorts confirms clinical observations of sex-specific disease cause and response to treatment among hypertensive patients, and mandate the identification of sex-specific hypertension genes/mechanisms. We developed and studied two congenic strains, S.R5A and S.R5B introgressing Dahl R-chromosome 5 segments into Dahl S chromosome 5 region spanning putative BP-f1 and BP-f2 QTLs. Radiotelemetric non-stressed 24-hour BP analysis at four weeks post-high salt diet (8% NaCl) challenge, identified only S.R5B congenic rats with lower SBP (-26.5 mmHg, P = 0.002), DBP (-23.7 mmHg, P = 0.004) and MAP (-25.1 mmHg, P = 0.002) compared with Dahl S female controls at four months of age confirming BP-f1 but not BP-f2 QTL on rat chromosome 5. The S.R5B congenic segment did not affect pulse pressure and relative heart weight indicating that the gene underlying BP-f1 does not influence arterial stiffness and cardiac hypertrophy. The results of our congenic analysis narrowed BP-f1 to chromosome 5 coordinates 134.9-141.5 Mbp setting up the basis for further fine mapping of BP-f1 and eventual identification of the specific gene variant accounting for BP-f1 effect on blood pressure.

Dahl (S x R) Congenic Strain Analysis Confirms and Defines a Chromosome 5 Female-Specific Blood Pressure Quantitative Trait Locus to <7 Mbp

PubMed Central

Herrera, Victoria L. M.; Pasion, Khristine A.; Moran, Ann Marie; Ruiz-Opazo, Nelson

2012-01-01

The detection of multiple sex-specific blood pressure (BP) quantitative trait loci (QTLs) in independent total genome analyses of F2 (Dahl S x R)-intercross male and female rat cohorts confirms clinical observations of sex-specific disease cause and response to treatment among hypertensive patients, and mandate the identification of sex-specific hypertension genes/mechanisms. We developed and studied two congenic strains, S.R5A and S.R5B introgressing Dahl R-chromosome 5 segments into Dahl S chromosome 5 region spanning putative BP-f1 and BP-f2 QTLs. Radiotelemetric non-stressed 24-hour BP analysis at four weeks post-high salt diet (8% NaCl) challenge, identified only S.R5B congenic rats with lower SBP (−26.5 mmHg, P = 0.002), DBP (−23.7 mmHg, P = 0.004) and MAP (−25.1 mmHg, P = 0.002) compared with Dahl S female controls at four months of age confirming BP-f1 but not BP-f2 QTL on rat chromosome 5. The S.R5B congenic segment did not affect pulse pressure and relative heart weight indicating that the gene underlying BP-f1 does not influence arterial stiffness and cardiac hypertrophy. The results of our congenic analysis narrowed BP-f1 to chromosome 5 coordinates 134.9–141.5 Mbp setting up the basis for further fine mapping of BP-f1 and eventual identification of the specific gene variant accounting for BP-f1 effect on blood pressure. PMID:22860086

Polychlorinated biphenyl concentrations, congener profiles, and ratios in the fat tissue, eggs, and plasma of snapping turtles (Chelydra s. serpentina) from the Ohio Basin of Lake Erie, USA.

PubMed

Dabrowska, H; Fisher, S W; Estenik, J; Kidekhel, R; Stromberg, P

2006-08-01

Concentrations and profiles of polychlorinated biphenyls (PCBs) were determined in three tissues of adult snapping turtles (Chelydra serpentina serpentina) from six locations in the Ohio Basin of Lake Erie to characterize tissue variation and geographic trends. The locations included the Ohio Areas of Concern, i.e., the Ashtabula, Black, and Maumee Rivers; the Ottawa River near Toledo; and two reference sites. Mean total PCBs were greatest in turtles from the Ottawa River followed by the Maumee, Ashtabula, and Black Rivers. All three types of samples-fat tissue (FT), eggs, and plasma-showed the same geographic trend in PCB levels. On a wet-weight basis, mean concentrations ranged from 2,148 to 18,669 ng/g in FT, from 183 to 3,683 ng/g in eggs, and from 18 to 201 ng/g in plasma. Across all sites, total PCB concentrations between the tissues were significantly correlated (0.001 < p < 0.005; Pearson correlation coefficient (r ( P )) was between 0.720 and 0.954). Two distinctly different profiles with respect to relative congener and homologue concentrations were found among the sites. One that included four of the six sites examined was characterized by hexa-chlorobiphenyl (hexa-CB) dominance followed by hepta-CBs, with PCBs no. 138 + 163, 153 + 132 + 105, and 180 being the most abundant congeners. The second profile, specific for turtles from the Ottawa River, was different from the first in that tetra-CBs were the most abundant congeners followed by hexa-CBs. Analysis of variance (ANOVA) indicated significant intertissue differences in the PCB homologue profiles, i.e., FT had a higher percentage of hepta-, octa-, and nona-CBs compared with eggs and plasma, whereas eggs showed a higher percentage of hexa-CBs. At any listed location, FT, eggs, and plasma had the same congener profile. An intertissue distribution of lipid-normalized individual congener concentrations examined by regression analyses revealed significant egg-FT, egg-plasma, and FT-plasma relations for

Congener specific determination and enantiomeric ratios of chiral polychlorinated biphenyls in striped dolphins (Stenella coeruleoalba) from the Mediterranean Sea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reich, S.; Schurig, V.; Jimenez, B.

1999-06-01

Blubber and liver samples from six striped dolphins (Stenella coeruleoalba) found dead in the Mediterranean Sea in 1989--1990 were tested for 37 coplanar and chiral polychlorinated biphenyls (PCBs), including the enantiomeric ratios of 9 chiral PCBs. The method includes a fractionation step using HPLC (PYE column) for separating the PCBs according to the number of chlorine atoms in the ortho positions. HRGC/ECD and HRGC/LRMS with an a chiral column (DB-5) were used to determine the PCB congeners. The enantiomeric ratios of nine chiral PCBs were determined by HRGC/LRMS (SIM) with a chiral column (Chirasil-Dex) and by MDGC as the confirmatorymore » technique. The total PCB concentration (sum of 37 congeners) ranged from 7.2 to 89.6 {micro}g/g (wet weight) and from 0.52 to 29.2 {micro}g/g (wet weight) for blubber and liver samples, respectively. PCB profiles were dominated by congeners 138, 153, 170, and 180. The toxic equivalent values (TEQ) ranged from 0.17 to 3.93 ng/g (wet weight) and from 0.02 to 0.73 ng/g (wet weight) for blubber and liver samples, respectively. PCBs 95, 132, 135, 149, and 176 revealed an enantiomeric excess of the second eluted enantiomer in almost all of the samples, whereas PCBs 136 and 174 were racemic or almost racemic. PCBs 88 and 91 were under the detection limits of the methodology used.« less

Effects of Estradiol on Learned Helplessness and Associated Remodeling of Hippocampal Spine Synapses in Female Rats

PubMed Central

Hajszan, Tibor; Szigeti-Buck, Klara; Sallam, Nermin L; Bober, Jeremy; Parducz, Arpad; MacLusky, Neil J; Leranth, Csaba; Duman, Ronald S

2009-01-01

Background Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in females is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant, desipramine. Considering the fact that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life may influence behavioral and synaptic responses to stress and depression. Methods Using electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n=70), under different conditions of estradiol exposure. Results Stress induced an acute and persistent loss of hippocampal spine synapses, while subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either prior to stress or prior to escape testing of nonstressed animals both increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. Conclusions These findings suggest that hippocampal spine synapse remodeling may be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression. PMID:19811775

Changes in ovarian function associated with circulating concentrations of estradiol before a GnRH-induced ovulation in beef cows

USDA-ARS?s Scientific Manuscript database

These studies were conducted to evaluate causes for differences in circulating concentrations of estradiol prior to a GnRH-induced ovulation and to determine if exogenous GnRH administration could alter LH secretion and subsequent follicular estradiol production. Beef cows (Experiment 1; n = 32, Ex...

COULD ETHINYL ESTRADIOL AFFECT THE POPULATION BIOLOGY OF CUNNER, TAUTOGOLABRUS ADSPERSUS

EPA Science Inventory

Endocrine disrupting chemicals in the environment may disturb the population dynamics of wildlife by affecting reproductive output and embryonic development of organisms. This study used a population model to evaluate whether ethinyl estradiol (EE2 could affect cunner Tautogolabr...

Mechanisms of estradiol-induced insulin secretion by the G protein-coupled estrogen receptor GPR30/GPER in pancreatic beta-cells.

PubMed

Sharma, Geetanjali; Prossnitz, Eric R

2011-08-01

Sexual dimorphism and supplementation studies suggest an important role for estrogens in the amelioration of glucose intolerance and diabetes. Because little is known regarding the signaling mechanisms involved in estradiol-mediated insulin secretion, we investigated the role of the G protein-coupled receptor 30, now designated G protein-coupled estrogen receptor (GPER), in activating signal transduction cascades in β-cells, leading to secretion of insulin. GPER function in estradiol-induced signaling in the pancreatic β-cell line MIN6 was assessed using small interfering RNA and GPER-selective ligands (G-1 and G15) and in islets isolated from wild-type and GPER knockout mice. GPER is expressed in MIN6 cells, where estradiol and the GPER-selective agonist G-1 mediate calcium mobilization and activation of ERK and phosphatidylinositol 3-kinase. Both estradiol and G-1 induced insulin secretion under low- and high-glucose conditions, which was inhibited by pretreatment with GPER antagonist G15 as well as depletion of GPER by small interfering RNA. Insulin secretion in response to estradiol and G-1 was dependent on epidermal growth factor receptor and ERK activation and further modulated by phosphatidylinositol 3-kinase activity. In islets isolated from wild-type mice, the GPER antagonist G15 inhibited insulin secretion induced by estradiol and G-1, both of which failed to induce insulin secretion in islets obtained from GPER knockout mice. Our results indicate that GPER activation of the epidermal growth factor receptor and ERK in response to estradiol treatment plays a critical role in the secretion of insulin from β-cells. The results of this study suggest that the activation of downstream signaling pathways by the GPER-selective ligand G-1 could represent a novel therapeutic strategy in the treatment of diabetes.

Mechanisms of Estradiol-Induced Insulin Secretion by the G Protein-Coupled Estrogen Receptor GPR30/GPER in Pancreatic β-Cells

PubMed Central

Sharma, Geetanjali

2011-01-01

Sexual dimorphism and supplementation studies suggest an important role for estrogens in the amelioration of glucose intolerance and diabetes. Because little is known regarding the signaling mechanisms involved in estradiol-mediated insulin secretion, we investigated the role of the G protein-coupled receptor 30, now designated G protein-coupled estrogen receptor (GPER), in activating signal transduction cascades in β-cells, leading to secretion of insulin. GPER function in estradiol-induced signaling in the pancreatic β-cell line MIN6 was assessed using small interfering RNA and GPER-selective ligands (G-1 and G15) and in islets isolated from wild-type and GPER knockout mice. GPER is expressed in MIN6 cells, where estradiol and the GPER-selective agonist G-1 mediate calcium mobilization and activation of ERK and phosphatidylinositol 3-kinase. Both estradiol and G-1 induced insulin secretion under low- and high-glucose conditions, which was inhibited by pretreatment with GPER antagonist G15 as well as depletion of GPER by small interfering RNA. Insulin secretion in response to estradiol and G-1 was dependent on epidermal growth factor receptor and ERK activation and further modulated by phosphatidylinositol 3-kinase activity. In islets isolated from wild-type mice, the GPER antagonist G15 inhibited insulin secretion induced by estradiol and G-1, both of which failed to induce insulin secretion in islets obtained from GPER knockout mice. Our results indicate that GPER activation of the epidermal growth factor receptor and ERK in response to estradiol treatment plays a critical role in the secretion of insulin from β-cells. The results of this study suggest that the activation of downstream signaling pathways by the GPER-selective ligand G-1 could represent a novel therapeutic strategy in the treatment of diabetes. PMID:21673097

The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-α production.

PubMed

Dimitrijević, Mirjana; Stanojević, Stanislava; Kuštrimović, Nataša; Mitić, Katarina; Vujić, Vesna; Aleksić, Iva; Radojević, Katarina; Leposavić, Gordana

2013-11-01

The phenotype and function of tissue macrophages substantially depend on the cellular milieu and biological effector molecules, such as steroid hormones, to which they are exposed. Furthermore, in female rats, aging is associated with the altered macrophage functioning and the increased estrogen level is followed by a decrease in that of progesterone. Therefore, the present study aimed to investigate the influence of estradiol/progesterone balance on rat macrophage function and phenotype throughout whole adult lifespan. We ovariectomized rats at the late prepubertal age or at the very end of reproductive lifespan, and examined the expression of ED2 (CD163, a marker of mature resident macrophages related to secretion of inflammatory mediators) on peritoneal macrophages and their ability to produce TNF-α and NO upon LPS-stimulation at different age points. In addition, to delineate direct and indirect effects of estrogen, we assessed the in vitro influence of different concentrations of 17β-estradiol on LPS-induced macrophage TNF-α and NO production. Results showed that: (a) the low frequency of ED2(high) cells amongst peritoneal macrophages of aged rats was accompanied with the reduced TNF-α, but not NO production; (b) estradiol level gradually increased following ovariectomy; (c) macrophage ED2 expression and TNF-α production were dependent on estradiol/progesterone balance and they changed in the same direction; (d) changes in estradiol/progesterone balance differentially affected macrophages TNF-α and NO production; and (e) estradiol exerted pro-inflammatory and anti-inflammatory effects on macrophages in vivo and in vitro, respectively. Overall, our study discloses that estradiol/progesterone balance contributes to the fine-tuning of rat macrophage secretory capacity, and adds to a better understanding of the ovarian steroid hormone role in the regulation of macrophage function, and its significance for the age-associated changes in innate immunity. �

Short-term estradiol replacement in postmenopausal women selectively mutes somatostatin's dose-dependent inhibition of fasting growth hormone secretion.

PubMed

Bray, M J; Vick, T M; Shah, N; Anderson, S M; Rice, L W; Iranmanesh, A; Evans, W S; Veldhuis, J D

2001-07-01

How estradiol stimulates pulsatile GH secretion in the human is not well understood. Here, we test the clinical hypothesis that estradiol stimulates GH secretion, in part, by opposing somatostatin's inhibition of GH release. To this end, 13 estrogen-withdrawn postmenopausal women received placebo or 1 mg micronized estradiol-17beta orally, twice daily for 14 days, in a prospectively randomized, patient-blinded, within-subject cross-over design. For each intervention, the dose-dependent suppressive actions of somatostatin were evaluated by infusing 0 (saline), 3, 10, 30, 100, or 300 microg/1.73 m(2).h somatostatin-14 continuously, iv, for 3 h, on separate mornings, in the fasting state, 48 h apart. Blood was sampled at 10-min intervals for 2 h before, for 3 h concurrently with, and for 1 h after each infusion. Serum GH concentrations were quantitated in an ultrasensitive chemiluminescence-based assay (detection threshold, 0.005 microg/L). In the estrogen-deficient milieu, constant iv somatostatin infusions inhibited steady-state serum GH concentrations (valley mean during the last 60 min of the infusion interval) in a dose-dependent manner (P < 10(-4) interventional effect). Maximally effective doses of somatostatin reduced the latter by 89 +/- 6.1% (mean +/- SEM) below the subject-specific preinfusion baseline. Estrogen administration increased the serum estradiol concentration from 12 +/- 1 to 245 +/- 35 pg/mL [42 +/- 4 to 920 +/- 110 pmol/L] (P < 10(-4)); decreased serum concentrations of LH (P = 0.018), FSH (P < 10(-4)), and insulin-like growth factor-I (P = 0.003); and elevated the fasting (6-h mean) serum GH concentration from 0.41 +/- 0.07 to 0.87 +/- 0.27 (P = 0.011). Estradiol supplementation did not alter somatostatin's maximal suppression of GH by 89 +/- 4.7% (P < 10(-4) below subject-specific preinfusion baseline), thus signifying unchanging somatostatin efficacy. In contrast, estradiol replacement significantly elevated the half-maximally inhibitory

High-dose estradiol improves cognition for women with AD: results of a randomized study.

PubMed

Asthana, S; Baker, L D; Craft, S; Stanczyk, F Z; Veith, R C; Raskind, M A; Plymate, S R

2001-08-28

To characterize the cognitive and neuroendocrine response to treatment with a high dose of estrogen for postmenopausal women with AD. Twenty postmenopausal women with AD were randomized to receive either 0.10 mg/day of 17 beta-estradiol by skin patch or a placebo patch for 8 weeks. Subjects were evaluated at baseline, at weeks 3, 5, and 8 during treatment, and again 8 weeks after treatment termination. During each visit, cognition was assessed with a battery of neuropsychological tests, and blood samples were collected to measure plasma estradiol as well as several other neuroendocrine markers of interest. Significant effects of estrogen treatment were observed on attention (Stroop Color Word Interference Test), verbal memory (Buschke Selective Reminding Test), and visual memory (Figure Copy/Memory). In addition, women treated with estrogen demonstrated improved performance on a test of semantic memory (Boston Naming Test) compared with subjects who received a placebo. Estrogen appeared to have a suppressive effect on the insulin-like growth factor (IGF) system such that plasma concentration of IGF binding protein-3 was significantly reduced and plasma levels of estradiol and IGF-I were negatively correlated during estrogen treatment. Administration of a higher dose of estrogen may enhance attention and memory for postmenopausal women with AD. Although these findings provide further clinical evidence to support a cognitive benefit of estrogen for women with AD, studies evaluating the effect of estradiol administration, in particular, using larger sample sizes and for longer treatment durations are warranted before the therapeutic potential of estrogen replacement for women with AD can be firmly established.

Simultaneous measurement of total Estradiol and Testosterone in human serum by isotope dilution liquid chromatography tandem mass spectrometry

PubMed Central

Zhou, Hui; Wang, Yuesong; Gatcombe, Matthew; Farris, Jacob; Botelho, Julianne C.; Caudill, Samuel P.; Vesper, Hubert W.

2017-01-01

Reliable measurement of total testosterone and estradiol is critical for their use as biomarkers of hormone related disorders in patient care and translation research. We developed and validated a mass spectrometry method to simultaneously quantify these analytes in human serum without chemical derivatization. Serum is equilibrated with isotopic internal standards and treated with acidic buffer to release hormones from their binding proteins. Lipids are isolated and polar impurities are removed by two serial liquid-liquid extraction steps. Total testosterone and estradiol are measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) in combination of positive and negative electrospray ionization modes. The method shows broad analytical measurement range for both testosterone 0.03–48.5 nM (0.75–1400 ng/dL) and estradiol 11.0–5138 pM (2.99–1400 pg/mL) and excellent agreement with certified reference materials (mean bias less than 2.1% to SRM 971, BCR 576, 577, and 578) and a high order reference method (mean bias 1.25% for testosterone and −0.84% for estradiol). The high accuracy of the method was monitored and certified by CDC Hormone Standardization (HoSt) Program for two years with mean bias −0.7% (95%CI: −1.6% to 0.2%) for testosterone and 0.1% (95%CI: −2.2% to 2.3%) for estradiol. The method precision over a 2-year period for Quality Control pools at low, medium and high concentrations was 2.7–2.9% for testosterone and 3.3–5.3% for estradiol. With the consistently excellent accuracy and precision, this method is readily applicable for high-throughput clinical and epidemiological studies. PMID:28801832

17β-Estradiol Reverses Leptin-Inducing Ovarian Cancer Cell Migration by the PI3K/Akt Signaling Pathway.

PubMed

Hoffmann, Marta; Fiedor, Elżbieta; Ptak, Anna

2016-11-01

Accumulating evidence suggests that leptin is expressed at higher levels in obese women and stimulates cell migration in epithelial cancers. However, the biology of ovarian cancer is different from others, mainly due to the production of estrogens because of the involvement of ovarian tissue, which is the main source of estrogens; as a result, the levels are at least 100- to 1000-fold higher than normal circulating levels. Thus, ovarian cancer tissues are exposed to 17β-estradiol, which promotes ovarian cancer cell migration and may modulate the effect of other hormones. Therefore, this study investigated the effects of 17β-estradiol (1 nmol/L) with leptin (1-40 ng/mL) at physiological levels, on the migration of OVCAR-3 and SKOV-3 ovarian cancer cells, and the expression levels and activity of metalloproteinases (MMPs) 2 and 9. Here, we found that leptin stimulated ovarian cancer cell line migration, which is mediated via the expression and activity of MMP-9 in the OVCAR-3 but not in the SKOV-3 cells. After the administration of 17β-estradiol and leptin, we observed antagonistic effects of 17β-estradiol on leptin-induced OVCAR-3 cell migration and MMP-9 expression and activity. Moreover, the antagonistic effect of 17β-estradiol on leptin-induced cancer cell migration was reversed by pretreatment of the cells with the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor. Taken together, our results, for the first time, show that in ovarian cancer cells ObR + /ER + , 17β-estradiol has an antagonistic effect on leptin-induced cell migration as well as MMP-9 expression and activity, which is mediated by the PI3K pathway. © The Author(s) 2016.

Enduring influences of peripubertal/adolescent stressors on behavioral response to estradiol and progesterone in adult female mice.

PubMed

Laroche, Julie; Gasbarro, Lauren; Herman, James P; Blaustein, Jeffrey D

2009-08-01

Exposure to stressors during particular stages of development leads to acute and long-term physiological and behavioral changes. We have reported that shipping mice during the peripubertal/adolescent period results in decreased induction of feminine sexual behavior by estradiol and progesterone in adult female mice. To study further the factors involved in this decreased behavioral response, female mice were exposed to a variety of experimental stressors when 6 wk old. Effects of peripubertal/adolescent exposure to these stressors on acute plasma corticosterone levels and changes in body weight and adult behavioral response to estradiol and progesterone were assessed. Although restraint for three daily 3-h periods, 36-h food deprivation, or a multiple stressor regimen acutely increased plasma corticosterone levels and reduced body weight, only exposure to particular doses of the bacterial endotoxin lipopolysaccharide (LPS; 1-1.5 mg/kg body weight, doses that induced moderate levels of sickness behavior in these studies) resulted in reduced behavioral response to estradiol and progesterone in adulthood. Like the effects of shipping, the effects of LPS on adult feminine sexual behavior appear most robust when injected at 6 wk old and are limited to exposure during a vulnerable period at approximately 4-6 wk of age. Therefore, an immune stressor during the peripubertal/adolescent period, but not restraint, food restriction, or a combined stressor, has an enduring influence on behavioral response to estradiol and progesterone. This demonstrates that the decreased response to estradiol and progesterone is not a general response to all stressors during this developmental stage.

Women Who are Married or Living as Married have Higher Salivary Estradiol and Progesterone than Unmarried Women

PubMed Central

BARRETT, EMILY S.; TRAN, VAN; THURSTON, SALLY W.; FRYDENBERG, HANNE; LIPSON, SUSAN F.; THUNE, INGER; ELLISON, PETER T.

2017-01-01

Objectives Extensive research has demonstrated that marriage and parenting are associated with lower testosterone levels in men, however, very little is known about associations with hormone concentrations in women. Two studies have found lower testosterone in relation to pair-bonding and motherhood in women, with several others suggesting that estradiol levels are lower among parous women than nulliparous women. Here, we examine estradiol and progesterone concentrations in relation to marriage and motherhood in naturally cycling, reproductive age women. Methods In 185 Norwegian women, estradiol and progesterone concentrations were assayed from waking saliva samples collected daily over the course of a menstrual cycle. Cycles were aligned on day 0, the day of ovulation. Mean periovulatory estradiol (days −7 to +6) and luteal progesterone (day +2 to +10) indices were calculated. Marital status and motherhood (including age of youngest child) were reported in baseline questionnaires. Multivariable linear regression models were used to examine associations between ovarian hormones, marital status, and motherhood. Results Women who were married or living as married had higher estradiol than unmarried women (β = 0.19; 95% CI: 0.02, 0.36) and higher luteal progesterone as well (β = 0.19; 95% CI: −0.01, 0.39). There were no notable differences in hormone levels in relationship to motherhood status. Conclusions Our results indicate that ovarian steroid hormones may be higher among women who are married or living as married, and suggest several possible explanations, however, additional research is needed to elucidate any causal relationships. PMID:25753399

Women who are married or living as married have higher salivary estradiol and progesterone than unmarried women.

PubMed

Barrett, Emily S; Tran, Van; Thurston, Sally W; Frydenberg, Hanne; Lipson, Susan F; Thune, Inger; Ellison, Peter T

2015-01-01

Extensive research has demonstrated that marriage and parenting are associated with lower testosterone levels in men, however, very little is known about associations with hormone concentrations in women. Two studies have found lower testosterone in relation to pair-bonding and motherhood in women, with several others suggesting that estradiol levels are lower among parous women than nulliparous women. Here, we examine estradiol and progesterone concentrations in relation to marriage and motherhood in naturally cycling, reproductive age women. In 185 Norwegian women, estradiol and progesterone concentrations were assayed from waking saliva samples collected daily over the course of a menstrual cycle. Cycles were aligned on day 0, the day of ovulation. Mean periovulatory estradiol (days -7 to +6) and luteal progesterone (day +2 to +10) indices were calculated. Marital status and motherhood (including age of youngest child) were reported in baseline questionnaires. Multivariable linear regression models were used to examine associations between ovarian hormones, marital status, and motherhood. Women who were married or living as married had higher estradiol than unmarried women (β = 0.19; 95% CI: 0.02, 0.36) and higher luteal progesterone as well (β = 0.19; 95% CI: -0.01, 0.39). There were no notable differences in hormone levels in relationship to motherhood status. Our results indicate that ovarian steroid hormones may be higher among women who are married or living as married, and suggest several possible explanations, however, additional research is needed to elucidate any causal relationships. © 2015 Wiley Periodicals, Inc.

Detection of 17 β-Estradiol in Environmental Samples and for Health Care Using a Single-Use, Cost-Effective Biosensor Based on Differential Pulse Voltammetry (DPV).

PubMed

Dai, Yifan; Liu, Chung Chiun

2017-03-29

Environmental estrogen pollution and estrogen effects on the female reproductive system are well recognized scientifically. Among the estrogens, 17 β-estradiol is a priority in environmental estrogen pollution, and it is also a major contributor to estrogen which regulates the female reproductive system. 17 β-estradiol is carcinogenic and has a tumor promotion effect relating to breast cancer, lung cancer and others. It also affects psychological well-being such as depression, fatigue and others. Thus, a simple method of detecting 17 β-estradiol will be important for both environmental estrogen pollution and health care. This study demonstrates a single-use, cost-effective 17 β-estradiol biosensor system which can be used for both environmental and health care applications. The bio-recognition mechanism is based on the influence of the redox couple, K₃Fe(CN)₆/K₄Fe(CN)₆ by the interaction between 17 β-estradiol antigen and its α-receptor (ER-α; α-estrogen antibody). The transduction mechanism is an electrochemical analytical technique, differential pulse voltammetry (DPV). The levels of 17 β-estradiol antigen studied were between 2.25 pg/mL and 2250 pg/mL; Phosphate buffered saline (PBS), tap water from the Cleveland regional water district, and simulated urine were used as the test media covering the potential application areas for 17 β-estradiol detection. An interference study by testosterone, which has a similar chemical structure and molecular weight as those of 17 β-estradiol, was carried out, and this 17 β-estradiol biosensor showed excellent specificity without any interference by similar chemicals.

Different responses of mesenteric artery from normotensive and spontaneously hypertensive rats to nitric oxide and its redox congeners.

PubMed

Orescanin, Zorana S; Milovanović, Slobodan R; Spasić, Snezana D; Jones, David R; Spasić, Mihajlo B

2007-01-01

The conversion of nitric oxide (NO*) into its congeners nitrosonium (NO(+)) and nitroxyl (HNO/NO(-)) ions may have important consequences for signal transduction and physiological responses. Manganese-containing superoxide dismutase (MnSOD) may convert NO. into its redox congeners. In our current work, we have examined the mechanism of sodium nitroprusside (SNP)-induced relaxation of arteries, with or without endothelium, from both normotensive and spontaneously hypertensive (SH) rats in the absence and presence of MnSOD. SNP induced a greater degree of relaxation in normotensive than in SH rats. MnSOD antagonized SNP-induced relaxation and effect was greater in normotensive than hypertensive rats. However, MnSOD even potentiated SNP-induced relaxation in mesenteric arteries with endothelium from SH rats. Our results indicate that HNO/NO(-)-mediated relaxation is more effective in mesenteric artery smooth muscle from SH rats than from normotensive rats and that vascular dysfunction in SH rats is not solely endothelium-derived but involves changes in vascular smooth muscles.

High estradiol and low progesterone are associated with high assertiveness in women.

PubMed

Blake, Khandis R; Bastian, Brock; O'Dean, Siobhan M; Denson, Thomas F

2017-01-01

Sexual selection theory posits that women are more selective than men are when choosing a mate. This evolutionary theory suggests that "choosiness" increases during the fertile window because the costs and benefits of mate selection are highest when women are likely to conceive. Little research has directly investigated reproductive correlates of choice assertion. To address this gap, in the present research we investigated whether fertility, estradiol, and progesterone influenced general assertiveness in women. We recruited 98 naturally cycling, ethnically diverse women. Using a within-subjects design and ovarian hormone concentrations at fertile and non-fertile menstrual cycle phases, we measured implicit assertiveness and self-reported assertive behavior. To see if fertility-induced high assertiveness was related to increased sexual motivation, we also measured women's implicit sexual availability and interest in buying sexy clothes. Results showed that high estradiol and low progesterone predicted higher assertiveness. Sexual availability increased during periods of high fertility. Low progesterone combined with high estradiol predicted greater interest in buying sexy clothes. Results held when controlling for individual differences in mate value and sociosexual orientation. Our findings support the role of fluctuating ovarian hormones in the expression and magnitude of women's assertiveness. High assertiveness during the fertile window may be a psychological adaptation that promotes mate selectivity and safeguards against indiscriminate mate choice when conception risk is highest. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changes in ovarian function associated with circulating concentrations of estradiol prior to a GnRH-induced ovulation in beef cows

USDA-ARS?s Scientific Manuscript database

Previous reports suggest increased circulating concentrations of estradiol prior to GnRH induced ovulation improved conception rates and pregnancy maintenance in beef cattle, and cultured granulosa cells from animals with high antral follicle numbers produced more estradiol and had increased express...

OXIDATION OF POLYCHLORINATED BIPHENYLS BY LIVER TISSUE SLICES FROM PHENOBARBITAL-PRETREATED MICE IS CONGENER-SPECIFIC AND ATROPSELECTIVE

PubMed Central

Wu, Xianai; Duffel, Michael; Lehmler, Hans-Joachim

2013-01-01

Mouse models are powerful tools to study the developmental neurotoxicity of polychlorinated biphenyls (PCBs); however, studies of the oxidation of chiral PCB congeners to potentially neurotoxic hydroxylated metabolites (OH-PCBs) in mice have not been reported. Here we investigate the atropselective oxidation of chiral PCB 91 (2,2',3,4',6-pentachlorobiphenyl), PCB 95 (2,2',3,5',6-pentachlorobiphenyl), PCB 132 (2,2',3,3',4,6'-hexachlorobiphenyl), PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl) and PCB 149 (2,2',3,4',5',6-hexachlorobiphenyl) to OH-PCBs in liver tissue slices prepared from female mice. The metabolite profile of PCB 136 typically followed the rank order 5-OH-PCB > 4-OH-PCB > 4,5-OH-PCB, and metabolite levels increased with PCB concentration and incubation time. A similar OH-PCB profile was observed with the other PCB congeners, with 5-OH-PCB:4-OH-PCB ratios ranging from 2 to 12. More 5-OH-PCB 136 was formed in liver tissue slices obtained from animals pretreated with phenobarbital (P450 2B inducer) or, to a lesser extent, dexamethasone (P450 2B and 3A enzyme inducer) compared to tissue slices prepared from vehicle-pretreated animals. The apparent rate of 5-OH-PCBs formation followed the approximate rank order PCB 149 > PCB 91 > PCB 132 ~ PCB 136 > PCB 95. Atropselective gas chromatography revealed a congener-specific atropisomeric enrichment of major OH-PCB metabolites. Comparison of our results with published OH-PCB patterns and chiral signatures (i.e., the direction and extent of the atropisomeric enrichment) from rat liver microsomal revealed drastic differences between both species, especially following induction of P450 2B enzymes. These species differences in the metabolism of chiral PCBs should be considered in developmental neurotoxicity studies of PCBs. PMID:24107130

Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation

PubMed Central

Cui, Yue; Franciszkiewicz, Katarzyna; Mburu, Yvonne K.; Mondot, Stanislas; Le Bourhis, Lionel; Premel, Virginie; Martin, Emmanuel; Kachaner, Alexandra; Duban, Livine; Ingersoll, Molly A.; Rabot, Sylvie; Jaubert, Jean; De Villartay, Jean-Pierre; Soudais, Claire; Lantz, Olivier

2015-01-01

Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%–10% in blood). Despite strong evolutionary conservation of the invariant TCR-α chain and restricting molecule MR1, this population is rare in laboratory mouse strains (≈0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-α locus and led to higher usage of the distal Vα segments, including Vα19. We generated a MAIThi congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory (CD44+) CD4–CD8lo/neg T cells with tissue-homing properties (CCR6+CCR7–). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18Rα, and IL-12Rβ and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptor γ (RORγt). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the MAIThi congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease. PMID:26524590

Use of specific radioimmunoassays to determine the renal clearance rates of estrone and 17. beta. -estradiol during the menstrual cycle. [Tritium tracer techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wright, K.; Collins, D.C.; Preedy, J.R.K.

Specific RIAs requiring ether extraction only were established for estrone and 17..beta..-estradiol both in plasma and in urine from the nonpregnant female. These assays were used to measure the renal clearance rates of estrone and of 17..beta..-estradiol in eight ambulatory women in the follicular and in the luteal phases of the menstrual cycle. The mean (+-SE) for the renal clearance rate of estrone was 0.71 +- 0.058 ml/min in the follicular phase and 1.26 +- 0.35 ml/min in the luteal phase. The mean (+-SE) renal clearance rate of 17..beta..-estradiol was 0.44 +- 0.055 ml/min in the follicular phase and 0.29more » +- 0.043 ml/min in the luteal phase. There was no significant difference in the renal clearance rates of either estrone or of 17..beta..-estradiol between the follicular and luteal phases of the cycle. The renal clearances of estrone and 17..beta..-estradiol were highly correlated (r = 0.84; P < 0.01). The renal clearance rate of estrone was significantly greater than that of 17..beta..-estradiol in both phases of the cycle (P < 0.01).« less

The role of 17β-estradiol metabolites in chromium-induced oxidative stress.

PubMed

Sawicka, Ewa; Długosz, Anna

2017-01-01

The increasing incidence of estrogen-dependent breast cancer and the presence in the environment of a large number of factors that interact with estrogen receptors have sparked interest in chemical influences on estrogen-dependent processes. In a previous work, the authors examined the interaction of estradiol with chromium. In the present article the importance of estradiol biotransformation in these interactions is investigated. There is no information in the available literature about the role of metabolites in exposure to chromium. It seems important because estradiol metabolites have various carcinogenic abilities and their formation during biotransformation could be increased or decreased by environmental enzyme inducers or inhibitors. The metabolites could play a detoxifying role or create a toxic synergism in free radical processes induced by chromium VI (CrVI). The aim of this study was to evaluate the influence of 2 17β-estradiol metabolites - 4-hydroxyestradiol (4-OHE2) and 16α-hydroxyestrone (16α-OHE1) - in conditions of oxidative stress caused by CrVI. Human blood, erythrocytes or mitochondria isolated from human placentas after natural deliveries were used in the experiments. The influence of CrVI, 4-OHE2 and 16-OHE1 on thiobarbituric acid reactive substances (TBARS), the hydroxyl radical (•OH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), and the interactions of the metabolites exposed to chromium expressed by these factors were examined. 4-OHE2 reduced the level of TBARS induced by CrVI in mitochondria (p < 0.05) and in erythrocytes (p < 0.05), and increased SOD activity (p < 0.05). 16α-OHE1 increased the activity of GST in erythrocytes exposed to CrVI (p < 0.05). The metabolites do not have toxic interactions with CrVI. On the contrary, they exhibited a protective effect. The mechanism of protection varied: 4-OHE2 decreased TBARS and increased SOD activity, while 16α-OHE1 increased GST

Enhanced accumulation of PCB congeners by Baltic Sea blue mussels, Mytilus edulis, with increased algae enrichment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilek, M.; Bjoerk, M.; Broman, D.

The objective of this study was to examine if natural variations in the quantity of phytoplankton-derived particulate and dissolved organic carbon influences the accumulation of polychlorinated biphenyls (PCBs) in the tissues of Baltic Sea blue mussels (Mytilus edulis L.). In a laboratory flow-through experiment the authors exposed M. edulis to the technical PCB mixture Aroclor{reg_sign} 1248 for 21 d at three different enrichments of the unicellular green algae Chlamydomonas sp., 0.10, 0.16, and 0.32 mg particulate organic carbon (POC)/L. Tissue and water concentrations were determined for seven PCB congeners and 21-d bioaccumulation factors were calculated against total water concentrations. Contrarymore » to what would be expected, an increase in algae enrichment from 0.10 to 0.32 mg POC/L resulted in an enhanced PCB accumulation by a factor of approx. 2. This increase in PCB accumulation was more pronounced for PCB congeners with lower hydrophobicity. These observations have implications for the design of laboratory accumulation studies and potentially for PCB accumulation and cycling in field populations of suspension-feeding mussels in response to changes in eutrophication status.« less

Determination of polychlorinated dibenzo-p-dioxin and dibenzofuran congeners in air particulate and marine sediment standard reference materials (SRMs).

PubMed

Chiu, C H; Turle, R; Poole, G; Thibert, B; Brubaker, W W; Schantz, M M; Wise, S A

2001-02-01

Due to the limited number of environmental matrix certified reference materials (CRMs) with assigned values for natural levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), an interlaboratory study was undertaken by the National Institute of Standards and Technology (NIST) and Environment Canada to establish reference concentration values for selected PCDD/Fs in two well-characterized NIST Standard Reference Materials (SRMs): SRM 1649a (Urban Dust) and SRM 1944 (New York/New Jersey Waterway Sediment). Results from 14 laboratories were used to provide reference values for the seventeen 2, 3, 7, 8-substituted PCDD/F congeners, the totals for individual tetra- through hepta-substituted PCDD/F homologues, and the total amount of tetra- through hepta-substituted PCDD/Fs. The mass fractions for the individual 2, 3, 7, 8-substituted congeners range from approximately 0.01 microg/kg to 7 microg/kg dry mass.

The Protective Effect of γ-aminobutyric Acid on Kidney Injury Induced by Renal Ischemia-reperfusion in Ovariectomized Estradiol-treated Rats.

PubMed

Talebi, Nahid; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Vafapour, Marzieh

2016-01-01

Renal ischemia-reperfusion injury (IRI) is one of the most important causes of kidney injury, which is possibly gender-related. This study was designed to investigate the role of γ-aminobutyric acid (GABA) against IRI in ovariectomized estradiol-treated rats. Thirty-five ovariectomized Wistar rats were used in six experimental groups. The first three groups did not subject to estradiol treatment and assigned as sham-operated, control, and GABA-treated groups. GABA (50 μmol/kg) and saline were injected in the treated and control groups 30 min before the surgery, respectively. The second three groups received the same treatments but received estradiol valerate (500 μg/kg, intramuscularly) 3 days prior to the surgery. The IRI was induced in the control and treated groups by clamping the renal artery for 45 min and then 24 h of reperfusion. All animals were sacrificed for the measurements. The serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score significantly increased in the IRI rats (P < 0.05). GABA significantly decreased the aforementioned parameters (P < 0.05). The uterus weight increased significantly in rats that received estradiol (P < 0.05). Serum and kidney levels of nitrite (nitric oxide metabolite) did not alter significantly. Serum level of malondialdehyde increased significantly in the ovariectomized rats exposed to IRI (P < 0.05). It seems that GABA improved IRI in ovariectomized rats. Estradiol was also nephroprotective against IRI. However, co-administration of estradiol and GABA could not protect the kidney against IRI.

Predictive value of repeated measurements of luteal progesterone and estradiol levels in patients with intrauterine insemination and controlled ovarian stimulation.

PubMed

Bakas, Panagiotis; Simopoulou, Maria; Giner, Maria; Drakakis, Petros; Panagopoulos, Perikles; Vlahos, Nikolaos

2017-10-01

The objective of this study is to assess if the difference of repeated measurements of estradiol and progesterone during luteal phase predict the outcome of intrauterine insemination. Prospective study. Reproductive clinic. 126 patients with infertility. Patients underwent controlled ovarian stimulation with recombinant FSH (50-150 IU/d). The day of IUI patients were given p.o natural micronized progesterone in a dose of 100 mg/tds. The area under the receiver characteristic operating curve (ROC curve) in predicting clinical pregnancy for % change of estradiol level on days 6 and 10 was 0.892 with 95% CI: 0.82-0.94. A cutoff value of change > -29.5% had a sensitivity of 85.7 with a specificity of 90.2. The corresponding ROC curve for % change of progesterone level was 0.839 with 95% CI: 0.76-0.90. A cutoff value of change > -33% had a sensitivity of 85 with a specificity of 75. The % change of estradiol and progesterone between days 6 and 10 has a predictive ability of pregnancy after IUI with COS of 89.2% and 83.4%, respectively. The addition of % of progesterone to % change of estradiol does not improve the predictive ability of % estradiol and should not be used.

Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.

PubMed

Al Abed, Alice Shaam; Sellami, Azza; Brayda-Bruno, Laurent; Lamothe, Valérie; Noguès, Xavier; Potier, Mylène; Bennetau-Pelissero, Catherine; Marighetto, Aline

2016-07-01

Because estrogens have mostly been studied in gonadectomized females, effects of chronic exposure to environmental estrogens in the general population are underestimated. Estrogens can enhance hippocampus-dependent memory through the modulation of information storage. However, declarative memory, the hippocampus-dependent memory of facts and events, demands more than abilities to retain information. Specifically, memory of repetitive events of everyday life such as "where I parked" requires abilities to organize/update memories to prevent proactive interference from similar memories of previous "parking events". Whether such organizational processes are estrogen-sensitive is unknown. We here studied, in intact young and aged adult mice, drinking-water (1μM) estradiol effects on both retention and organizational components of hippocampus-dependent memory, using a radial-maze task of everyday-like memory. Demand on retention vs organization was manipulated by varying the time-interval separating repetitions of similar events. Estradiol increased performance in young and aged mice under minimized organizational demand, but failed to improve the age-associated memory impairment and diminished performance in young mice under high organizational demand. In fact, estradiol prolonged mnemonic retention of successive events without improving organization abilities, hence resulted in more proactive interference from irrelevant memories. c-Fos imaging of testing-induced brain activations showed that the deterioration of young memory was associated with dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our findings support the view that estradiol is promnesic but also reveal that such property can paradoxically impair memory. These findings have important outcomes regarding health issues relative to the impact of environmental estrogens in the general population. Copyright © 2016 Elsevier Ltd. All rights reserved.

GC/MS ANALYSIS OF PCB CONGENERS IN BLOOD OF THE HARBOR SEAL PHOCA VITULINA FROM SAN FRANCISCO BAY

EPA Science Inventory

Here we report a validated technique for quantifying up to 20 specific PCB congeners in 1-2 g samples of whole blood with a detection limit below 1 ng/g (ppb) wet weight. Specimens were analyzed from 14 harbor seals sampled in south San Francisco Bay, California during 1991-1992....

Tissue distribution of HCH and DDT congeners and human health risk associated with consumption of fish collected from Kabul River, Pakistan.

PubMed

Aamir, Muhammad; Khan, Sardar; Nawab, Javed; Qamar, Zahir; Khan, Anwarzeb

2016-03-01

Distribution of hexachlorocyclohexane (HCH) and dichlorodiphenyltrichloroethane (DDT) congeners in tissues of four different fish species and their associated potential health risks to local consumers are presented in this paper. The average ∑(HCHs+DDTs) concentration in Glyptothorax punjabensis (214ngg(-1) wet weight (ww)) (carnivores) was found higher than Tor putitora (155ngg(-1) ww) (herbivores). The distribution of ∑(HCHs+DDTs) in all fish tissues was found in order of liver>muscle>stomach>gills. The profile of congeners (β-HCH/∑HCH from 0.29-0.47) indicated that all selected fish species were contaminated with HCH because of its recent usage in the study area. Furthermore, DDT profile ((DDE+DDD)/∑DDT from 0.61-0.78) showed that fish contamination with DDT originated from past usage and long-time degradation mechanism. The average estimated daily dietary intake of ∑HCHs (15.0ngkg(-1) day(-1)) was higher than ∑DDTs (12.5ngkg(-1) day(-1)) by the local consumers via fish consumption. On the basis of both 50th and 95th percentile exposure levels, the carcinogenic hazard ratios for DDT and its congeners were exceeded one (safe limit) for all fish species, indicating a great potential cancer risk for local consumers with life time consumption of contaminated fish collected from Kabul River. Copyright © 2015 Elsevier Inc. All rights reserved.

Age-specific reference values for serum FSH and estradiol levels throughout the reproductive period.

PubMed

Grisendi, Valentina; Spada, Elena; Argento, Cindy; Plebani, Maddalena; Milani, Silvano; Seracchioli, Renato; Volpe, Annibale; La Marca, Antonio

2014-06-01

High serum day 3 FSH levels are associated with poor ovarian reserve and reduced fertility, but the interpretation of FSH values according to age is still not univocal. The purpose of this study was to determine age-dependent reference values in women with regular menstrual cycles and FSH as a guide for specialists. The study was performed at the Department of Mother-Infant of a University-based tertiary care centre. One-hundred ninety-two healthy normal menstruating women were recruited for the study. All patients attended the department on menstrual cycle day 3 for a blood sample for FSH and estradiol determination. A linear relationship between FSH or estradiol serum levels and age was observed. The FSH level increased by 0.11 IU for every year of age (1 IU for every 9 years of age). The values of FSH and estradiol corresponding to the 5th, 25th, 50th, 75th, 95th centiles for any specific age have been calculated. Serum FSH levels need to be interpreted according to age-dependent reference values. Serum FSH levels on 95th centile for any age may represent a warning sign for reduced ovarian reserve.

Vitex agnus castus as prophylaxis for osteopenia after orchidectomy in rats compared with estradiol and testosterone supplementation.

PubMed

Sehmisch, S; Boeckhoff, J; Wille, J; Seidlova-Wuttke, D; Rack, T; Tezval, M; Wuttke, W; Stuermer, K M; Stuermer, E K

2009-06-01

Osteoporosis research undertaken in males is rare and there are only a few therapeutic options. Phytoestrogens might be a safe alternative for prophylaxis. Sixty 3-month-old male rats were orchidectomized and divided into five groups. The groups either received soy-free food (C), estradiol (E), testosterone (T) or Vitex agnus castus in different concentrations (AC high/AC low) for 12 weeks. The tibia metaphysis was tested biomechanically and histomorphometrically. The AC high group reached 87% of the biomechanical values of the estradiol group and was significantly superior to the control group. Testosterone supplementation resulted in poor biomechanical properties. The cortical bone parameters of the AC group were similar to the control group, while supplementation with estradiol and testosterone demonstrated a reduction of cortical bone. The AC high group reached 88.4% of trabecular bone area, 80.7% of trabecular number and 66.9% of the number of trabecular nodes compared with estradiol supplementation. Vitex agnus castus demonstrated osteoprotective effects in males. It preserves the cortical as well as the trabecular bone and might be a safe alternative for HRT. Testosterone supplementation has positive effects on trabecular bone, which are concurrently counteracted by the loss of cortical bone. (c) 2008 John Wiley & Sons, Ltd.

Effects of nitric oxide and its congeners on sickle red blood cell deformability

PubMed Central

Belanger, Andrea M.; Keggi, Christian; Kanias, Tamir; Gladwin, Mark T.; Kim-Shapiro, Daniel B.

2015-01-01

BACKGROUND Sickle cell disease is characterized by hemoglobin (Hb) polymerization upon deoxygenation. Polymerization causes the sickle cells to become rigid and misshapen (sickling). Red blood cell (RBC) dehydration greatly increases polymerization. Cycles of sickling and unsickling cause an influx of calcium that leads to loss of potassium via the calcium-activated Gardos channel which dehydrates the cells leading to increased polymerization. In this study effects of NO and its congeners on RBC deformability were examined, focusing on sickle red blood cells. STUDY DESIGN AND METHODS Red blood cells from patients with sickle cell disease and from non-patients were exposed to various compounds that release NO or its congeners. Intracellular calcium was increased using a calcium ionophore or cycling of oxygen tension for sickle red blood cells. Deformability was measured by laser-assisted osmotic gradient ektacytometry. RESULTS Consistent with a previous report, sodium nitroprusside (SNP) was found to protect against calcium-induced loss of deformability in normal red blood cells, but (contrary to some previous reports) no effect of any NO donors was observed when calcium influx was not induced. Importantly, in studies of deoxygenation-induced dehydration of sickle RBCs, SNP resulted in substantial improvements in deformability (p=0.036) and hydration (p=0.024). Sodium nitrite showed similar trends. SNP was shown to have no effect on calcium influx, but reduced potassium efflux. CONCLUSION These data suggest SNP and perhaps certain nitrogen oxides (like nitrite) inhibit the Gardos channel and may be able to protect sickle cells from dehydration and thereby improve outcome in the disease. PMID:25912054

Effects of nitric oxide and its congeners on sickle red blood cell deformability.

PubMed

Belanger, Andrea M; Keggi, Christian; Kanias, Tamir; Gladwin, Mark T; Kim-Shapiro, Daniel B

2015-10-01

Sickle cell disease (SCD) is characterized by hemoglobin polymerization upon deoxygenation. Polymerization causes the sickle cells to become rigid and misshapen (sickling). Red blood cell (RBC) dehydration greatly increases polymerization. Cycles of sickling and unsickling cause an influx of calcium that leads to loss of potassium via the calcium-activated Gardos channel, which dehydrates the cells leading to increased polymerization. In this study the effects of nitric oxide (NO) and its congeners on RBC deformability were examined, focusing on sickle RBCs (sRBCs). RBCs from patients with SCD and from nonpatients were exposed to various compounds that release NO or its congeners. Intracellular calcium was increased using a calcium ionophore or cycling of oxygen tension for sRBCs. Deformability was measured by laser-assisted osmotic gradient ektacytometry. Consistent with a previous report, sodium nitroprusside (SNP) was found to protect against calcium-induced loss of deformability in normal RBCs, but (contrary to some previous reports) no effect of any NO donors was observed when calcium influx was not induced. Importantly, in studies of deoxygenation-induced dehydration of sRBCs, SNP resulted in substantial improvements in deformability (p = 0.036) and hydration (p = 0.024). Sodium nitrite showed similar trends. SNP was shown to have no effect on calcium influx, but reduced potassium efflux. These data suggest that SNP and perhaps certain nitrogen oxides (like nitrite) inhibit the Gardos channel and may be able to protect sickle cells from dehydration and thereby improve outcome in the disease. © 2015 AABB.

G protein-coupled estrogen receptor is required for the neuritogenic mechanism of 17β-estradiol in developing hippocampal neurons.

PubMed

Ruiz-Palmero, Isabel; Hernando, Maria; Garcia-Segura, Luis M; Arevalo, Maria-Angeles

2013-06-15

Estradiol promotes neuritogenesis in developing hippocampal neurons by a mechanism involving the upregulation of neurogenin 3, a Notch-regulated transcription factor. In this study we have explored whether G-protein coupled estrogen receptor 1 (GPER) participates in this hormonal action. GPER agonists (17β-estradiol, G1, ICI 182,780) increased neurogenin 3 expression and neuritogenesis in mouse primary hippocampal neurons and this effect was blocked by the GPER antagonist G15 and by a siRNA for GPER. In addition, GPER agonists increased Akt phosphorylation in ser473, which is indicative of the activation of phosphoinositide-3-kinase (PI3K). G15 or GPER silencing prevented the estrogenic induction of Akt phosphorylation. Furthermore, the PI3K inhibitor wortmannin prevented the effect of G1 and estradiol on neurogenin 3 expression and the effect of estradiol on neuritogenesis. These findings suggest that GPER participates in the control of hippocampal neuritogenesis by a mechanism involving the activation of PI3K signaling. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Differential regulation of gonadotropin-releasing hormone (GnRH) neuron activity and membrane properties by acutely-applied estradiol: dependence on dose and estrogen receptor subtype

PubMed Central

Chu, Zhiguo; Andrade, Josefa; Shupnik, Margaret A.; Moenter, Suzanne M.

2009-01-01

GnRH neurons are critical to controlling fertility. In vivo, estradiol can inhibit or stimulate GnRH release depending on concentration and physiological state. We examined rapid, non-genomic effects of estradiol. Whole-cell recordings were made of GnRH neurons in brain slices from ovariectomized mice with ionotropic GABA and glutamate receptors blocked. Estradiol was bath-applied and measurements completed within 15 min. Estradiol from high physiological (preovulatory) concentrations (100pM) to 100nM enhanced action potential firing, reduced afterhyperpolarizing potential (AHP) and increased slow afterdepolarization (sADP) amplitudes, and reduced IAHP and enhanced IADP. The reduction of IAHP was occluded by prior blockade of calcium-activated potassium channels. These effects were mimicked by an estrogen receptor (ER) β-specific agonist and were blocked by the classical receptor antagonist ICI182780. ERα or GPR30 agonists had no effect. The acute stimulatory effect of high physiological estradiol on firing rate was dependent on signaling via protein kinase A. In contrast, low physiological levels of estradiol (10pM) did not affect intrinsic properties. Without blockade of ionotropic GABA and glutamate receptors, however, 10pM estradiol reduced firing of GnRH neurons; this was mimicked by an ERα agonist. ERα agonists reduced the frequency of GABA transmission to GnRH neurons; GABA can excite to these cells. In contrast, ERβ agonists increased GABA transmission and postsynaptic response. These data suggest rapid intrinsic and network modulation of GnRH neurons by estradiol is dependent upon both dose and receptor subtype. In cooperation with genomic actions, non-genomic effects may play a role in feedback regulation of GnRH secretion. PMID:19403828

Short-term estradiol administration in aging ovariectomized rats provides lasting benefits for memory and the hippocampus: a role for insulin-like growth factor-I.

PubMed

Witty, Christine F; Gardella, Layne P; Perez, Maria C; Daniel, Jill M

2013-02-01

We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle age exhibited enhanced spatial memory and increased levels of estrogen receptor (ER)-α in the hippocampus long after estradiol treatment was terminated. The implication for cognition of increased levels of ERα resulting from prior estradiol exposure is unknown. In the absence of estrogens, growth factors, including IGF-I, can induce ERα-mediated transcription through ligand-independent mechanisms. Our current goal was to determine whether IGF-I mediates the ability of short-term exposure to estradiol to exert long-term effects on cognition and the hippocampus of aging females. Ovariectomized middle-aged rats were implanted with estradiol or cholesterol vehicle capsules. After 40 days, all capsules were removed and drug treatments were initiated. Half of each hormone treatment group received chronic intracerebroventricular delivery of the IGF-I receptor antagonist JB1, and the other half received artificial cerebrospinal fluid vehicle. Rats were tested on a spatial memory radial-arm maze task and hippocampi were immunostained for proteins of interest by Western blotting. As expected, previous treatment with estradiol enhanced spatial memory and increased levels of ERα in the hippocampus. JB1 reversed these effects. Previous treatment with estradiol resulted in lasting increases in levels of IGF-I receptors and phosphorylation of ERK/MAPK, a downstream signaling molecule of both ERα and IGF-I receptors, and increased levels of the ERα-regulated protein, choline acetyltransferase. JB1 blocked effects on ERK/MAPK and choline acetyltransferase. Results indicate that activation of IGF-I receptors is necessary for prior estradiol exposure to exert lasting impact on the hippocampus and memory.

The regulation of progesterone receptor by 17 beta estradiol and tamoxifen in the Zr-75-1 human breast cancer cell line in defined medium.

PubMed

Allegra, J C; Korat, O; Do, H M; Lippman, M

1981-01-01

The regulation of progesterone receptor by 17 beta estradiol and tamoxifen in the ZR-75-1 human breast cancer cell line in defined medium is described. ZR-75-1 cells maintained in serum free hormone supplemented medium minus estradiol lack progesterone receptor activity. Readdition of estradiol to these cells leads to a marked stimulation of progesterone receptor activity (0 to greater than 100 fmols of specifically bound progesterone per million cells). Tamoxifen (10(-6)M-10(-8)M) does not stimulate progesterone receptor activity in this cell line. The presence of progesterone receptor activity is not directly related to growth. Withdrawal of insulin in the continued presence of estradiol has no effect on progesterone receptor concentration although net cell growth ceases. Conversely, withdrawal of estradiol in the continued presence of insulin induces a cessation of net cell growth accompanied by a loss of all progesterone receptor activity within 3-5 days.

OOCYTE ENVELOPE PROTEINS AND VITELLOGENIN IN MALE SHEEPHEAD MINNOW EXPOSED TO ESTRADIOL

EPA Science Inventory

Oocyte Envelope Proteins and Vitellogenin Expression in Male Sheepshead Minnows Exposed to Estradiol (Abstract). To be presented at the 22nd Annual Meeting of the Society of Environmental Toxicology and Chemistry: Changing Environmental Awareness: Societal Concerns and Scientifi...

Norelgestromin/ethinyl estradiol intravenous infusion formulation optimization, stability and compatibility testing: A case study to overcome polysorbate 80 interference in chromatographic analysis.

PubMed

Abdallah, Inas A; Hammell, Dana C; Hassan, Hazem E; Stinchcomb, Audra L

2016-06-05

Norelgestromin/ethinyl estradiol is a progestin/estrogen combination hormonal contraceptive indicated for the prevention of pregnancy in women. The very poor solubility and wettability of these drugs, along with their high potency (adsorption issues), give rise to difficulties in designing intravenous (IV) formulations to assess absolute bioavailability of products containing both drugs. The purpose of this study was to develop an IV formulation, evaluate its stability under different conditions and evaluate its compatibility with IV sets for potential use in absolute bioavailability studies in humans. Also, a selective high-performance liquid chromatography (HPLC) method for quantification of ethinyl estradiol and norelgestromin in polysorbate 80 matrix was developed and validated. Norelgestromin/ethinyl estradiol IV solution was prepared using sterile water for injection with 2.5% ethanol and 2.5% polysorbate 80 as a cosolvent/surfactant system to obtain a final drug solution of 25μg ethinyl estradiol and 252μg norelgestromin from a concentrated stock drug solution. The stabilities of the concentrated stock and IV solutions were assessed after storing them in the refrigerator (3.7±0.6°C) and at room temperature (19.5±0.5°C), respectively. Additional studies were conducted to examine the stability of the IV solution using an Alarias(®) low sorbing IV administration set with and without an inline filter. The solution was allowed to drip at 1mL/min over a 60min period. Samples were obtained at the beginning, middle and end of the 60min duration. The chemical stability was evaluated for up to 10 days. Norelgestromin and ethinyl estradiol concentration, purity, and degradant levels were determined using the HPLC method. The norelgestromin/ethinyl estradiol IV formulation met the chemical stability criteria when tested on day 1 through day 9 (216h). Norelgestromin concentrations assayed in stock and IV solutions were in the range of 90.0-98.5% and 90

Linking habitat use of Hudson River striped bass to accumulation of polychlorinated biphenyl congeners

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashley, J.T.F.; Secor, D.H.; Zlokovitz, E.

2000-03-15

Since 1976, the commercial striped bass fishery in the Hudson River (NY) has been closed due to total polychlorinated biphenyl (t-PCB) concentrations that exceed the US Food and Drug Administration's advisory level of 2 {micro}g/g-wet weight. Extensive monitoring of Hudson River striped bass demonstrated much more variability in t-PCB levels among individual striped bass than could be explained by their age, sex, or lipid contents. To investigate the possible role of differential habitat use among subpopulations of striped bass in controlling their PCB exposures, 70 fish collected throughout the Hudson River estuary and Long Island Sound in 1994--1995 were analyzedmore » for PCB congeners, and their lifetime migration behaviors were estimated by otolith microchemistry. The mean salinity encountered during the fish's last growth season prior to capture was inversely correlated with the t-PCB body burden. Striped bass permanently residing in fresh and oligohaline portions of the estuary adjacent to known PCB sources had elevated t-PCB levels and congeneric patterns with higher proportions of di-, tri-, and tetrachlorobiphenyls. Conversely, fish spending the majority of their life in more saline waters of the estuary or migrating frequently throughout the salinity gradient contained lower PCB levels composed of more highly chlorinated congeners. The approach used in this study allows habitat use to be incorporated into exposure assessments for anadromous fish species such as striped bass.« less

Effects of Estradiol on Post-Traumatic Stress Disorder Symptoms

DTIC Science & Technology

2010-03-01

Steroid Metabolism pathways 34 Figure 6. HPG Axis 35 Chapter 3 Figure 1. Effect of 7, 14, and 22 Days of...87 Treatment on Plasma CORT in OVX Sprague-Dawley Rats that were also Immobilization Stressed for 22 -days Figure 3. Effect of Early...for 22 -days Figure 5. Effect of Estradiol, Selective ERα Agonist, and ERβ Agonist 90 Treatment on Pre-Pulse Inhibition in OVX Sprague-Dawley

Relationship between Carotenoids, Retinol, and Estradiol Levels in Older Women

PubMed Central

Maggio, Marcello; de Vita, Francesca; Lauretani, Fulvio; Bandinelli, Stefania; Semba, Richard D.; Bartali, Benedetta; Cherubini, Antonio; Cappola, Anne R.; Ceda, Gian Paolo; Ferrucci, Luigi

2015-01-01

Background. In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2) in a cohort of late post-menopausal women. Methods. We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998–2000) by High-Performance Liquid Chromatography. Estradiol and testosterone (T) levels were assessed by Radioimmunometry (RIA) and testosterone-to-estradiol ratio (T/E2), as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1) and further adjusted for other confounders including Body Mass Index (BMI) BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2) were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. Results. After adjustment for age, α-carotene (β ± SE = −0.01 ± 0.004, p = 0.02) and β-carotene (β ± SE = −0.07 ± 0.02, p = 0.0007) were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01). After adjustment for other confounders (Model 2), the inverse relationship between α-carotene (β ± SE = −1.59 ± 0.61, p = 0.01), β-carotene (β ± SE = −0.29 ± 0.08, p

Relationship between Carotenoids, Retinol, and Estradiol Levels in Older Women.

PubMed

Maggio, Marcello; de Vita, Francesca; Lauretani, Fulvio; Bandinelli, Stefania; Semba, Richard D; Bartali, Benedetta; Cherubini, Antonio; Cappola, Anne R; Ceda, Gian Paolo; Ferrucci, Luigi

2015-08-05

In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2) in a cohort of late post-menopausal women. We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998-2000) by High-Performance Liquid Chromatography. Estradiol and testosterone (T) levels were assessed by Radioimmunometry (RIA) and testosterone-to-estradiol ratio (T/E2), as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1) and further adjusted for other confounders including Body Mass Index (BMI) BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2) were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. After adjustment for age, α-carotene (β ± SE = -0.01 ± 0.004, p = 0.02) and β-carotene (β ± SE = -0.07 ± 0.02, p = 0.0007) were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01). After adjustment for other confounders (Model 2), the inverse relationship between α-carotene (β ± SE = -1.59 ± 0.61, p = 0.01), β-carotene (β ± SE = -0.29 ± 0.08, p = 0.0009), and E2 persisted whereas the

The α-fetoprotein knock-out mouse model suggests that parental behavior is sexually differentiated under the influence of prenatal estradiol

PubMed Central

Keller, Matthieu; Pawluski, Jodi L.; Brock, Olivier; Douhard, Quentin; Bakker, Julie

2010-01-01

In rodent species, sexual differentiation of the brain for many reproductive processes depends largely on estradiol. This was recently confirmed again by using the α-fetoprotein knockout (AFP-KO) mouse model, which lacks the protective actions of α-fetoprotein against maternal estradiol and as a result represents a good model to determine the contribution of prenatal estradiol to the sexual differentiation of the brain and behavior. Female AFP-KO mice were defeminized and masculinized with regard to their neuroendocrine responses as well as sexual behavior. Since parental behavior is also strongly sexually differentiated in mice, we used the AFP-KO mouse model here to ask whether parental responses are differentiated prenatally under the influence of estradiol. It was found that AFP-KO females showed longer latencies to retrieve pups to the nest and also exhibited lower levels of crouching over the pups in the nest in comparison to WT females. In fact, they resembled males (WT and AFP-KO). Other measures of maternal behavior, for example the incidence of infanticide, tended to be higher in AFP-KO females than in WT females but this increase failed to reach statistical significance. The deficits observed in parental behavior of AFP-KO females could not be explained by any changes in olfactory function, novelty recognition or anxiety. Thus our results suggest that prenatal estradiol defeminizes the parental brain in mice. PMID:20109458

PROLACTIN LEVELS DO NOT RISE AMONG TRANSGENDER WOMEN TREATED WITH ESTRADIOL AND SPIRONOLACTONE.

PubMed

Bisson, Jason R; Chan, Kelly J; Safer, Joshua D

2018-04-30

Existing transgender treatment guidelines suggest that for transfeminine hormone treatment there is a need to monitor prolactin levels. Also, recent studies suggest that use of cyproterone acetate as an adjunctive anti-androgen during transgender hormone treatment may elevate serum prolactin. We sought to determine whether the reported relationship between transfeminine estradiol treatment and hyperprolactinemia would be evident when the regimen used spironolactone as the adjunctive anti-androgen. Estradiol levels, testosterone levels, prolactin levels, and BMI as well as prescribed spironolactone dosage were extracted from the electronic medical records of 98 de-identified transgender women treated with estrogen therapy at the Endocrinology Clinic at Boston Medical Center. Up to 6 years of data were available for some patients. We found no statistically significant relationship between prolactin and any of the other measures. No estrogen dose associated elevations in prolactin were found. None of the patients were diagnosed with prolactinoma. Our data suggest that there may be no significant rise in prolactin when transgender women are treated with estrogen along with spironolactone as the adjunct anti-androgen, and that it may be unnecessary to monitor prolactin in women on this treatment combination. BMI = body mass index; BMC = Boston Medical Center; HT = hormone therapy; ENIGI = European Network for the Investigation of Gender Incongruence; E2 = estradiol; LCMS/MS = liquid chromatography tandem mass spectrometry; T = testosterone.

Dietary Exposure to Individual Polybrominated Diphenyl Ether Congeners BDE-47 and BDE-99 Alters Innate Immunity and Disease Susceptibility in Juvenile Chinook Salmon.

PubMed

Arkoosh, Mary R; Van Gaest, Ahna L; Strickland, Stacy A; Hutchinson, Greg P; Krupkin, Alex B; Dietrich, Joseph P

2015-06-02

Polybrominated diphenyl ethers (PBDEs), used as commercial flame-retardants, are bioaccumulating in threatened Pacific salmon. However, little is known of PBDE effects on critical physiological functions required for optimal health and survival. BDE-47 and BDE-99 are the predominant PBDE congeners found in Chinook salmon collected from the Pacific Northwest. In the present study, both innate immunity (phagocytosis and production of superoxide anion) and pathogen challenge were used to evaluate health and survival in groups of juvenile Chinook salmon exposed orally to either BDE-47 or BDE-99 at environmentally relevant concentrations. Head kidney macrophages from Chinook salmon exposed to BDE-99, but not those exposed to BDE-47, were found to have a reduced ability in vitro to engulf foreign particles. However, both congeners increased the in vitro production of superoxide anion in head kidney macrophages. Salmon exposed to either congener had reduced survival during challenge with the pathogenic marine bacteria Listonella anguillarum. The concentration response curves generated for these end points were nonmonotonic and demonstrated a requirement for using multiple environmentally relevant PBDE concentrations for effect studies. Consequently, predicting risk from toxicity reference values traditionally generated with monotonic concentration responses may underestimate PBDE effect on critical physiological functions required for optimal health and survival in salmon.

Candidate chromosome 1 disease susceptibility genes for Sjogren’s syndrome xerostomia are narrowed by novel NOD.B10 congenic mice

PubMed Central

Mongini, Patricia K. A.; Kramer, Jill M.; Ishikawa, Tomo-o; Herschman, Harvey; Esposito, Donna

2014-01-01

Sjogren’s syndrome (SS) is characterized by salivary gland leukocytic infiltrates and impaired salivation (xerostomia). Cox-2 (Ptgs2) is located on chromosome 1 within the span of the Aec2 region. In an attempt to demonstrate that COX-2 drives antibody-dependent hyposalivation, NOD.B10 congenic mice bearing a Cox-2flox gene were generated. A congenic line with non-NOD alleles in Cox-2-flanking genes failed manifest xerostomia. Further backcrossing yielded disease-susceptible NOD.B10 Cox-2flox lines; fine genetic mapping determined that critical Aec2 genes lie within a 1.56 to 2.17 Mb span of DNA downstream of Cox-2. Bioinformatics analysis revealed that susceptible and non-susceptible lines exhibit non-synonymous coding SNPs in 8 protein-encoding genes of this region, thereby better delineating candidate Aec2 alleles needed for SS xerostomia. PMID:24685748

17beta-Estradiol and testosterone in drainage and runoff from poultry litter applications to tilled and no-till crop land under irrigation.

PubMed

Jenkins, Michael B; Endale, Dinku M; Schomberg, Harry H; Hartel, Peter G; Cabrera, Miguel L

2009-06-01

Thirteen million [corrected] metric tons of poultry litter are produced annually by poultry producers in the U.S. Poultry litter contains the sex hormones estradiol and testosterone, endocrine disruptors that have been detected in surface waters. The objective of this study was to evaluate the potential impact of poultry litter applications on estradiol and testosterone concentrations in subsurface drainage and surface runoff in irrigated crop land under no-till and conventional-till management. We conducted an irrigation study in fall of 2001 and spring of 2002. Four treatments, no-till plus poultry litter, conventional-till plus poultry litter, no-till plus conventional fertilizer, and conventional-till plus conventional fertilizer, were evaluated. Flow-weighted concentration and load ha(-1) of the two hormones were measured in drainage and runoff. Soil concentrations of estradiol and testosterone were measured. Based on comparisons to the conventional fertilizer (and control) treatments, poultry litter did not add to the flow-weighted concentration or load ha(-1) of either estradiol or testosterone in subsurface drainage or surface runoff. Significant differences were, however, observed between tillage treatments: flow-weighted concentrations of estradiol were greater for no-till than conventional-till plots of the June irrigation; and runoff loads of both estradiol and testosterone were less from no-till than conventional-till plots for the November irrigation. Although the differences between no-till and conventional-tillage appeared to affect the hydrologic transport of both hormones, the differences appeared to have inconsequential environmental impact.

Contraception containing estradiol valerate and dienogest--advantages, adherence and user satisfaction.

PubMed

Graziottin, A

2014-10-01

The contraceptive pill containing estradiol valerate and dienogest meets women's requests for: a more natural contraceptive, that is reliable and easy to use, with positive cosmetic effects; less intense and shorter bleeding, reduced anaemia and increased vital energy; reduced dysmenorrhoea and all the specific cycle-related symptoms linked to a drop in oestrogen and the related systemic inflammation, the result of a hormone free interval (HFI) of just two days; with a good impact on sexuality and overall well-being, all associated with a high level of efficacy: (uncorrected Pearl Index: 0.79; corrected: 0.42). Women would prefer more natural hormonal contraception, with high reliability, good tolerability, a simple dosing schedule and possibly some health advantages. To evaluate what the pill containing estradiol valerate and dienogest can offer women and the best way to communicate this opportunity, after 4 years of growing clinical use. A review of literature plus the Author's clinical experience. The new pill containing estradiol valerate and dienogest may satisfy women's need for: a more natural hormonal contraceptive with a low hormone dosage, high reliability and good tolerability; a simple dosing schedule (one pill per day for 28 days); a positive cosmetic effect on the skin; lighter and shorter withdrawal bleeding, improved anaemia, less fatigue and higher vital energy; reduced dysmenorrhoea and a dramatic reduction in all symptoms thanks to a shorter Hormone Free Interval (HFI) of just two days. The new pill is an option for all women taking hormonal contraception who would like a more natural choice; for those who have never used hormonal contraception and may consider this new opportunity positively, for those who suffer from various menstrual symptoms, related inflammation ("a shorter HFI means much fewer or no symptoms") and, possibly for pre-menopausal women, an opportunity to combine excellent contraception with a definite improvement in their well

Tamoxifen and estradiol improved locomotor function and increased spared tissue in rats after spinal cord injury: their antioxidant effect and role of estrogen receptor alpha.

PubMed

Mosquera, Laurivette; Colón, Jennifer M; Santiago, José M; Torrado, Aranza I; Meléndez, Margarita; Segarra, Annabell C; Rodríguez-Orengo, José F; Miranda, Jorge D

2014-05-02

17β-Estradiol is a multi-active steroid that imparts neuroprotection via diverse mechanisms of action. However, its role as a neuroprotective agent after spinal cord injury (SCI), or the involvement of the estrogen receptor-alpha (ER-α) in locomotor recovery, is still a subject of much debate. In this study, we evaluated the effects of estradiol and of Tamoxifen (an estrogen receptor mixed agonist/antagonist) on locomotor recovery following SCI. To control estradiol cyclical variability, ovariectomized female rats received empty or estradiol filled implants, prior to a moderate contusion to the spinal cord. Estradiol improved locomotor function at 7, 14, 21, and 28 days post injury (DPI), when compared to control groups (measured with the BBB open field test). This effect was ER-α mediated, because functional recovery was blocked with an ER-α antagonist. We also observed that ER-α was up-regulated after SCI. Long-term treatment (28 DPI) with estradiol and Tamoxifen reduced the extent of the lesion cavity, an effect also mediated by ER-α. The antioxidant effects of estradiol were seen acutely at 2 DPI but not at 28 DPI, and this acute effect was not receptor mediated. Rats treated with Tamoxifen recovered some locomotor activity at 21 and 28 DPI, which could be related to the antioxidant protection seen at these time points. These results show that estradiol improves functional outcome, and these protective effects are mediated by the ER-α dependent and independent-mechanisms. Tamoxifen׳s effects during late stages of SCI support the use of this drug as a long-term alternative treatment for this condition. Copyright © 2014 Elsevier B.V. All rights reserved.

Low-Temperature Catalytic Decomposition of 130 Tetra- to Octa-PCDD/Fs Congeners over CuOX and MnOX Modified V2O5/TiO2-CNTs with the Assistance of O3.

PubMed

Zhao, Rixiao; Jin, Dongdong; Yang, Hangsheng; Lu, Shengyong; Potter, Phillip M; Du, Cuicui; Peng, Yaqi; Li, Xiaodong; Yan, Jianhua

2016-10-07

In this study, a reliable and steady PCDD/F generation system was utilized to investigate the performance of catalysts, in which 130 congeners of tetra- to octapolychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) vapors were studied under simulated flue gas with/without O 3 . TiO 2 and carbon nanotubes (CNTs) supported vanadium oxides (VO X /TiO 2 -CNTs) modified with MnO X and CuO X , which were reported to be beneficial to the decomposition of model molecules, were found to have a negative effect on the removal of real PCDD/Fs in the simulated flue gas without O 3 . Moreover, the addition of MnO X presented different effects depending on whether CuO X existed in catalysts or not, which was also contrary to its effects on the degradation of model molecules. In an O 3 -containing atmosphere, low chlorination level PCDD/Fs congeners were removed well over VO X -MnO X /TiO 2 -CNTs, while high chlorination level PCDD/Fs congeners were removed well over VO X -CuO X /TiO 2 -CNTs. Fortunately, all PCDD/Fs congeners decomposed well over VO X -MnO X -CuO X /TiO 2 -CNTs. Finally, the effects of tetra- to octachlorination level for the adsorption and degradation behaviors of PCDD/Fs congeners were also investigated.

Fructose-rich diet and insulin action in female rat heart: Estradiol friend or foe?

PubMed

Bundalo, Maja; Romic, Snjezana; Tepavcevic, Snezana; Stojiljkovic, Mojca; Stankovic, Aleksandra; Zivkovic, Maja; Koricanac, Goran

2017-09-15

Increased intake of fructose in humans and laboratory animals is demonstrated to be a risk factor for development of metabolic disorders (insulin resistance, metabolic syndrome, type 2 diabetes) and cardiovascular diseases. On the other hand, estradiol is emphasized as a cardioprotective agent. The main goal of this review is to summarize recent findings on damaging cardiac effects of fructose-rich diet in females, mostly experimental animals, and to evaluate protective capacity of estradiol. Published results of our and other research groups indicate mostly detrimental effects of fructose-rich diet on cardiac insulin signaling molecules, glucose and fatty acid metabolism, nitric oxide production and ion transport, as well as renin-angiotensin system and inflammation. Some of these processes are involved in cardiac insulin signal transmission, others are regulated by insulin or have an influence on insulin action. Administration of estradiol to ovariectomized female rats, exposed to increased intake of fructose, was mostly beneficial to the heart, but sometimes it was ineffective or even detrimental, depending on the particular processes. We believe that these data, carefully translated to human population, could be useful for clinicians dealing with postmenopausal women susceptible to metabolic diseases and hormone replacement therapy. Copyright © 2017. Published by Elsevier B.V.

The folic acid combined with 17-β estradiol produces antidepressant-like actions in ovariectomized rats forced to swim.

PubMed

Molina-Hernández, Miguel; Téllez-Alcántara, N Patricia; Olivera-López, Jorge I; Jaramillo, M Teresa

2011-01-15

Folic acid or 17-β estradiol produces antidepressant effects, either alone or combined with several antidepressants. However, the antidepressant-like actions of folic acid combined with 17-β estradiol in the forced swimming test (FST) have not been tested before. Thus, in the present study, ovariectomized female rats received folic acid (5.0 nmol/i.c.v., P<0.05; 10.0 nmol/ i.c.v., P<0.05; or 50mg/kg, P<0.05, p.o.; 75.0; mg/kg, P<0.05, p.o.), or fluoxetine (20.0mg/kg, P<0.05; 25.0mg/kg, P<0.05) or 17-β estradiol (10.0 μg/rat, P<0.05; 20.0 μg/rat, P<0.05) and they displayed reduced immobility by increasing swimming behavior when they were tested in the FST. Combination of subthreshold doses of folic acid (2.5 nmol/i.c.v.; or 25.0mg/kg, p.o.) with subthreshold doses of 17-β estradiol (5.0 μg/rat, P<0.05) or with subthreshold doses of fluoxetine (15.0mg/kg, P<0.05) produced antidepressant-like actions. Ketanserin was used to evaluate the participation of the drugs used in the serotonergic pathway; ketanserin cancelled the antidepressant-like actions of the several combinations used. In conclusion, folic acid alone or combined with estradiol or fluoxetine in the FST reduced immobility in the FST. These antidepressant-like actions probably were due to modifications of the serotonergic system since swimming behavior was increased and these effects were cancelled by ketanserin. Copyright © 2010 Elsevier Inc. All rights reserved.

Estradiol impairs the antiproliferative and proapoptotic effect of Zoledronic acid in hormone sensitive breast cancer cells in vitro.

PubMed

Gschwantler-Kaulich, Daphne; Weingartshofer, Sigrid; Grunt, Thomas W; Mairhofer, Mario; Tan, Yen; Gamper, Jutta; Singer, Christian F

2017-01-01

Zoledronic acid (ZA) has antiresorptive effects and protects from bone metastasis in women with early breast cancer. In addition, in postmenopausal women with endocrine responsive breast cancer ZA prolongs DFS. The exact mechanism is still unclear. We have therefore investigated the effect of increasing concentrations of ZA in breast cancer cell lines in the absence or presence of estradiol to mimic the hormonal environment in vitro. Using assays for cell proliferation (EZ4U, BrdU) and cell death (Annexin/PI), we have analyzed the dose-dependent antiproliferative and pro-apoptotic effects of ZA in two hormone sensitive cell lines (MCF-7 and T47D) and a hormone insensitive, triple negative cell line (MDA-MB-231) in the presence of 0, 1 and 10 nM estradiol. In the absence of estradiol, ZA exerts dose-dependent antiproliferative and pro-apoptotic antitumor effects in both, hormone sensitive (MCF-7, T47D) and -insensitive (MDA-MB-231) breast cancer cell lines (p<0.0001). In the presence of estradiol, the antitumoral effect of ZA was significantly decreased only in the hormone sensitive MCF-7 and T47D cell lines (p = 0.0008 and p = 0.0008, respectively). We have demonstrated that estradiol impairs the antiproliferative and proapoptotic effect of ZA in hormone sensitive, but not in hormone insensitive breast cancer cell lines. Our findings provide a possible explanation for the differential effect of ZA on DFS in pre- and postmenopausal patients with hormone sensitive early breast cancer, which has been demonstrated clinically. We further hypothesize that endocrine insensitive tumors such as triple negative breast cancer (TNBC) should benefit from ZA irrespective of their menopausal status.

EFFECTS OF ETHYNYL ESTRADIOL EXPOSURE ON REPRODUCTIVE PARAMETERS IN AN ESTUARINE FISH

EPA Science Inventory

This study investigated the impact of ethynyl estradiol (EE2) on reproductive success of cunner, Tautogolabrus adspersus. EE2 is the estrogen used in human contraceptives and is released into the aquatic environment in sewage treatment effluent. Reproductively active male and fem...

Pregnancy rates after ewes were treated with estradiol-17beta and oxytocin.

USDA-ARS?s Scientific Manuscript database

Cervical dilation may improve transcervical sheep embryo-transfer procedures, if the cervical dilation method does not reduce pregnancy rates. This experiment was conducted to determine whether estradiol-17beta-oxytocin treatment, which dilates the cervix in luteal-phase ewes, affects pregnancy rat...

Pregnancy-induced gingivitis and OMICS in dentistry: in silico modeling and in vivo prospective validation of estradiol-modulated inflammatory biomarkers.

PubMed

Gürsoy, Mervi; Zeidán-Chuliá, Fares; Könönen, Eija; Moreira, José C F; Liukkonen, Joonas; Sorsa, Timo; Gürsoy, Ulvi K

2014-09-01

Pregnancy-associated gingivitis is a bacterial-induced inflammatory disease with a remarkably high prevalence ranging from 35% to 100% across studies. Yet little is known about the attendant mechanisms or diagnostic biomarkers that can help predict individual susceptibility for rational personalized medicine. We aimed to define inflammatory proteins in saliva, induced or inhibited by estradiol, as early diagnostic biomarkers or target proteins in relation to pregnancy-associated gingivitis. An in silico gene/protein interaction network model was developed by using the STITCH 3.1 with "experiments" and "databases" as input options and a confidence score of 0.700 (high confidence). Salivary estradiol, interleukin (IL)-1β and -8, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-2, -8, and -9, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 levels from 30 women were measured prospectively three times during pregnancy and twice during postpartum. In silico analysis revealed that estradiol interacts with IL-1β and -8 by an activation link when the "actions view" was consulted. In saliva, estradiol concentrations associated positively with TIMP-1 and negatively with MPO and MMP-8 concentrations. When the gingival bleeding on probing percentage (BOP%) was included in the model as an effect modifier, the only association, a negative one, was found between estradiol and MMP-8. Throughout gestation, estradiol modulates the inflammatory response by inhibiting neutrophilic enzymes, such as MMP-8. The interactions between salivary degradative enzymes and proinflammatory cytokines during pregnancy suggest promising ways to identify candidate biomarkers for pregnancy-associated gingivitis, and for personalized medicine in the field of dentistry. Finally, we call for greater investments in, and action for biomarker research in periodontology and dentistry that have surprisingly lagged behind in personalized medicine compared to other fields, such as cancer research.

Pregnancy-Induced Gingivitis and OMICS in Dentistry: In Silico Modeling and in Vivo Prospective Validation of Estradiol-Modulated Inflammatory Biomarkers

PubMed Central

Zeidán-Chuliá, Fares; Könönen, Eija; Moreira, José C. F.; Liukkonen, Joonas; Sorsa, Timo; Gürsoy, Ulvi K.

2014-01-01

Abstract Pregnancy-associated gingivitis is a bacterial-induced inflammatory disease with a remarkably high prevalence ranging from 35% to 100% across studies. Yet little is known about the attendant mechanisms or diagnostic biomarkers that can help predict individual susceptibility for rational personalized medicine. We aimed to define inflammatory proteins in saliva, induced or inhibited by estradiol, as early diagnostic biomarkers or target proteins in relation to pregnancy-associated gingivitis. An in silico gene/protein interaction network model was developed by using the STITCH 3.1 with “experiments” and “databases” as input options and a confidence score of 0.700 (high confidence). Salivary estradiol, interleukin (IL)-1β and -8, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-2, -8, and -9, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 levels from 30 women were measured prospectively three times during pregnancy and twice during postpartum. In silico analysis revealed that estradiol interacts with IL-1β and -8 by an activation link when the “actions view” was consulted. In saliva, estradiol concentrations associated positively with TIMP-1 and negatively with MPO and MMP-8 concentrations. When the gingival bleeding on probing percentage (BOP%) was included in the model as an effect modifier, the only association, a negative one, was found between estradiol and MMP-8. Throughout gestation, estradiol modulates the inflammatory response by inhibiting neutrophilic enzymes, such as MMP-8. The interactions between salivary degradative enzymes and proinflammatory cytokines during pregnancy suggest promising ways to identify candidate biomarkers for pregnancy-associated gingivitis, and for personalized medicine in the field of dentistry. Finally, we call for greater investments in, and action for biomarker research in periodontology and dentistry that have surprisingly lagged behind in personalized medicine compared to other fields

Development and evaluation of polymer nanoparticles for oral delivery of estradiol to rat brain in a model of Alzheimer's pathology.

PubMed

Mittal, G; Carswell, H; Brett, R; Currie, S; Kumar, M N V Ravi

2011-03-10

The purpose of this study was to develop tween 80 (T-80) coated polylactide-co-glycolide (PLGA) nanoparticles that can deliver estradiol to the brain upon oral administration. Estradiol containing nanoparticles were made by a single emulsion technique and T-80 coating was achieved by incubating the re-constituted nanoparticles at different concentrations of T-80. The process of T-80 coating on the nanoparticles was optimized and the pharmacokinetics of estradiol nanoparticles was studied as a function of T-80 coating. The nanoparticles were then evaluated in an ovariectomized (OVX) rat model of Alzheimer's disease (AD) that mimics the postmenopausal conditions. The nanoparticles bound T-80 were found to proportionally increase from 9.72 ± 1.07 mg to 63.84 ± 3.59 mg with an increase in the initial concentration T-80 from 1% to 5% and were stable in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Orally administered T-80 coated nanoparticles resulted in significantly higher brain estradiol levels after 24h (1.969 ± 0.197 ng/g tissue) as compared to uncoated ones (1.105 ± 0.136 ng/g tissue) at a dose of 0.2mg/rat, suggesting a significant role of surface coating. Moreover, these brain estradiol levels were almost similar to those obtained after administration of the same dose of drug suspension via 100% bioavailable intramuscular route (2.123 ± 0.370 ng/g tissue), indicating the increased fraction of bioavailable drug reaching the brain when administered orally. Also, the nanoparticle treated group was successful in preventing the expression of amyloid beta-42 (Aβ42) immunoreactivity in the hippocampus region of brain. Together, the results indicate the potential of nanoparticles for oral delivery of estradiol to brain. Copyright © 2010 Elsevier B.V. All rights reserved.

DEVELOPMERNT OF A LOW-LEVEL ANALYTICAL METHOD FOR CO-PLANAR PCB CONGENERS IN SOIL/SEDIMENT MATRICES USING GC/ECD.

EPA Science Inventory

The method development is on-going in the Region 10 Laboratory. The conditions of the separation technique is complete. The MDLs have been determined to be between 3 to 6 ppt in marine sediment for co-planar PCB congeners #77; #81; #126 and #169. The procedure has been used fo...

Sex differences in creatine kinase after acute heavy resistance exercise on circulating granulocyte estradiol receptors.

PubMed

Wolf, Megan R; Fragala, Maren S; Volek, Jeff S; Denegar, Craig R; Anderson, Jeffrey M; Comstock, Brett A; Dunn-Lewis, Courtenay; Hooper, David R; Szivak, Tunde K; Luk, Hui-Ying; Maresh, Carl M; Häkkinen, Keijo; Kraemer, William J

2012-09-01

Previous research has shown reduced tissue disruption and inflammatory responses in women as compared to men following acute strenuous exercise. While the mechanism of this action is not known, estrogen may reduce the inflammatory response through its interaction with granulocytes. The purpose of this study was to determine if estrogen receptor β expression on granulocytes is related to sex differences in tissue disruption in response to an acute heavy resistance exercise protocol. Seven healthy, resistance-trained, eumenorrheic women (23 ± 3 years, 169 ± 9.1 cm, 66.4 ± 10.5 kg) and 8 healthy, resistance-trained men (25 ± 5 years, 178 ± 6.7 cm, 82.3 ± 9.33 kg) volunteered to participate in the study. Subjects performed an acute resistance exercise test consisting of six sets of five squats at 90% of the subject's one repetition maximum. Blood samples were obtained pre-, mid-, post-, and 1-, 6-, and 24-h postexercise. Blood samples were analyzed for 17-β-estradiol by ELISA, creatine kinase by colorimetric enzyme immunoassay, and estradiol receptors on circulating granulocytes through flow cytometry. Men had higher CK concentrations than women at baseline/control. Men had significantly higher CK concentrations at 24-h postexercise than women. No significant changes in estradiol β receptors were expressed on granulocytes after exercise or between sexes. While sex differences occur in CK activity in response to strenuous eccentric exercise, they may not be related to estradiol receptor β expression on granulocytes. Thus, although there are sex differences in CK expression following acute resistance exercise, the differences may not be attributable to estrogen receptor β expression on granulocytes.

Localization of /sup 3/H-estradiol in the reproductive organs of male and female baboons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weaker, F.J.; Sheridan, P.J.

1982-05-01

The uptake and retention of radiolabeled estradiol by both the male and female reproductive organs were examined in the baboon. Two male and two female baboons were injected intracardially with 1 microgram/kg body weight of /sup 3/H-estradiol and two animals, one male and one female, were injected with both labeled and 100 micrograms/kg body weight of unlabeled estradiol. One and a half hours after the injections, the animals were sacrificed and the uterus, cervix, vagina, oviduct, seminal vesicles, and prostate gland were removed and processed for autoradiography. The stratified squamous epithelia of the cervix and vagina demonstrated a light uptakemore » of the label in the germinative, but not in the superficial cell layers. The columnar cells lining the oviduct and uterine glands were labeled, whereas the luminal epithelium of the uterus and the glandular epithelia of the seminal vesicles and prostate gland did not sequester the tritiated steroid. The interstitial cells of all the organs studied demonstrated a moderate to heavy uptake of the radioactivity, whereas the smooth muscle cells were lightly labeled except in the vagina, in which these cells displayed a moderate number of silver grains.« less

Differential vulnerability to adverse nutritional conditions in male and female rats: Modulatory role of estradiol during development.

PubMed

Pinos, Helena; Carrillo, Beatriz; Díaz, Francisca; Chowen, Julie A; Collado, Paloma

2018-01-01

Many studies have shown the importance of an adequate nutritional environment during development to optimally establish the neurohormonal circuits that regulate feeding behavior. Under- or over-nutrition during early stages of life can lead to alterations in the physiology and brain networks that control food intake, resulting in a greater vulnerability to suffer maladjustments in energy metabolism in adulthood. These alterations produced by under- or over-nourishment during development differ between males and females, as does the modulatory action that estradiol exerts on the alterations produced by malnutrition. Estradiol regulates metabolism and brain metabolic circuits through the same transcription factor pathway, STAT3, that leptin and ghrelin use to program feeding circuits. Although more research is needed to disentangle the actual role of estradiol during development on the programming of feeding circuits, a synergistic role together with leptin and/or ghrelin might be hypothesized. Copyright © 2017 Elsevier Inc. All rights reserved.

Relative congener scaling of Polychlorinated dibenzo-p-dioxins and dibenzofurans to estimate building fire contributions in air, surface wipes, and dust samples.

PubMed

Pleil, Joachim D; Lorber, Matthew N

2007-11-01

The United States Environmental Protection Agency collected ambient air samples in lower Manhattan for about 9 months following the September 11, 2001 World Trade Center (WTC) attacks. Measurements were made of a host of airborne contaminants including volatile organic compounds, polycyclic aromatic hydrocarbons, asbestos, lead, and other contaminants of concern. The present study focuses on the broad class of polychlorinated dibenzo-p-dioxins (CDDs) and dibenzofurans (CDFs) with specific emphasis on the 17 CDD/CDF congeners that exhibit mammalian toxicity. This work is a statistical study comparing the internal patterns of CDD/CDFs using data from an unambiguous fire event (WTC) and other data sets to help identify their sources. A subset of 29 samples all taken between September 16 and October 31, 2001 were treated as a basis set known to be heavily impacted by the WTC building fire source. A second basis set was created using data from Los Angeles and Oakland, CA as published by the California Air Resources Board (CARB) and treated as the archetypical background pattern for CDD/CDFs. The CARB data had a congener profile appearing similar to background air samples from different locations in America and around the world and in different matrices, such as background soils. Such disparate data would normally be interpreted with a qualitative pattern recognition based on congener bar graphs or other forms of factor or cluster analysis that group similar samples together graphically. The procedure developed here employs aspects of those statistical methods to develop a single continuous output variable per sample. Specifically, a form of variance structure-based cluster analysis is used to group congeners within samples to reduce collinearity in the basis sets, new variables are created based on these groups, and multivariate regression is applied to the reduced variable set to determine a predictive equation. This equation predicts a value for an output variable

Estradiol-modified prolactin secretion independently of action potentials and Ca2+ and blockade of outward potassium currents in GH3 cells.

PubMed

Sánchez, Manuel; Suárez, Lorena; Cantabrana, Begoña; Bordallo, Javier

2017-01-01

Estrogens facilitate prolactin (PRL) secretion acting on pituitary cells. In GH 3 cells, estradiol induces acute action potentials and oscillations of intracellular Ca 2+ associated with the secretagogue function. Estradiol modulates several ion channels which may affect the action potential rate and the release of PRL in lactotroph cells, which might depend on its concentration. The aims were to characterize the acute effect of supraphysiological concentrations of estradiol on Ca 2+ and noninactivating K + currents and measure the effect on the spontaneous action potentials and PRL release in the somatolactotroph cell line, GH 3 . Electrophysiological studies were carried out by voltage- and current-clamp techniques and ELISA determination of PRL secretion. Pharmacological concentrations of estradiol (above 1 μM), without a latency period, blocked Ca 2+ channels and noninactivating K + currents, including the large-conductance voltage- and Ca 2+ -activated K + channels (BK), studied in whole-cell nystatin perforated and in excided inside-out patches of GH 3 and CHO cells, transiently transfected with the human α-pore forming subunit of BK. The effect on BK was contrary to the agonist effect associated with the regulatory β 1 -subunits of the BK, which GH 3 cells lack, but its transient transfection did not modify the noninactivating current blockade, suggesting a different mechanism of regulation. Estradiol, at the same concentration range, acutely decreased the frequency of action potentials, an expected effect as consequence of the Ca 2+ channel blockade. Despite this, PRL secretion initially increased, followed by a decrease in long-term incubations. This suggests that, in GH 3 cells, supraphysiological concentrations of estradiol modulating PRL secretion are partially independent of extracellular Ca 2+ influx.

Human uterine and placental arteries exhibit tissue-specific acute responses to 17β-estradiol and estrogen-receptor-specific agonists.

PubMed

Corcoran, Jemma J; Nicholson, Christopher; Sweeney, Michèle; Charnock, Jayne C; Robson, Stephen C; Westwood, Melissa; Taggart, Michael J

2014-05-01

The discrete regulation of vascular tone in the human uterine and placental circulations is a key determinant of appropriate uteroplacental blood perfusion and pregnancy success. Humoral factors such as estrogen, which increases in the placenta and maternal circulation throughout human pregnancy, may regulate these vascular beds as studies of animal arteries have shown that 17β-estradiol, or agonists of estrogen receptors (ER), can exert acute vasodilatory actions. The aim of this study was to compare how acute exposure to ER-specific agonists, and 17β-estradiol, altered human placental and uterine arterial tone in vitro. Uterine and placental arteries were isolated from biopsies obtained from women with uncomplicated pregnancy delivering a singleton infant at term. Vessels were mounted on a wire myograph, exposed to the thromboxane receptor agonist U46619 (10(-6) M), and then incubated with incremental doses (5 min, 0.03-30 µM) of either 17β-estradiol or agonists specific for the ERs ERα (PPT), ERβ (DPN) or the G-protein-coupled estrogen receptor GPER-1 (G1). ERα and ERβ mRNA expression was assessed. 17β-estradiol, PPT and DPN each relaxed myometrial arteries (P < 0.05) in a manner that was partly endothelium-dependent. In contrast, 17β-estradiol or DPN relaxed placental arteries (maximum relaxation to 42 ± 1.1 or 47.6 ± 6.53% of preconstriction, respectively) to a lesser extent than myometrial arteries (to 0.03 ± 0.03 or 8.0 ± 1.0%) and in an endothelial-independent manner whereas PPT was without effect. G1 exposure did not inhibit the constriction of myometrial nor placenta arteries. mRNA expression of ERα and ERβ was greater in myometrial arteries than placental arteries. ER-specific agonists, and 17β-estradiol, differentially modulate the tone of uterine versus placental arteries highlighting that estrogen may regulate human uteroplacental blood flow in a tissue-specific manner.

USING BASE-SPECIFIC SALMONELLA TESTER STRAINS TO CHARACTERIZE THE TYPES OF MUTATION INDUCED BY BENZIDINE AND BENZIDINE CONGENERS AFTER REDUCTIVE METABOLISM

EPA Science Inventory

Abstract
Benzidine, 4-aminobiphenyl, 3,3'-dichlorobenzidine HCl, 3,3'-dimethylbenzidine, 3,3'- dimethoxybenzidine and benzidine congener-based dye trypan blue were mutagenic in Salmonella typhimurium TAl 00 only with metabolic activation. It was found that a hamster liver 89 ...

Estradiol and Progesterone Administration After pMCAO Stimulates the Neurological Recovery and Reduces the Detrimental Effect of Ischemia Mainly in Hippocampus.

PubMed

Perez-Alvarez, Maria Jose; Mateos, Laura; Alonso, Alvaro; Wandosell, Francisco

2015-12-01

Epidemiological studies have suggested a differential response, males versus female, in stroke incidence and prognosis. These divergences in brain response after damage are based mostly on hormonal differences. To date, estradiol and progesterone administered independently have demonstrated neuroprotection after ischemia in animal models. Nonetheless, contradictory results were revealed using a combined administration. In order to evaluate the effects of combinatorial treatment administered after ischemia induction, we used two different approaches: in vivo and in vitro models. Male rats which underwent permanent middle cerebral artery occlusion were treated with a combination of estradiol/progesterone at 6, 24 and 48 h after injury and sacrificed at 54 h post-ischemia. The rat brains were evaluated for reactive gliosis, NeuN-positive neurons, levels of synapse-associated proteins and activity levels of PI3K/Akt/GSK3/β-catenin survival pathway. Also, primary cortical neurons were subjected to oxygen and glucose deprivation for 17 h and returned to a normal environment in the presence of estradiol or estradiol/progesterone. Cell viability was evaluated, and activity levels of the PI3K/Akt/GSK3/β-catenin pathway. Our results indicate that some beneficial effects of estradiol were abolished in the presence of progesterone, particularly in the cerebral cortex (core). However, the combinatorial treatment showed positive effects in the hippocampus.

Therapeutic Efficacy of a Combination Therapy of Topical 17α-Estradiol and Topical Minoxidil on Female Pattern Hair Loss: A Noncomparative, Retrospective Evaluation.

PubMed

Choe, Sung Jay; Lee, Solam; Choi, Jaewoong; Lee, Won-Soo

2017-06-01

A variety of agents have been used to treat female pattern hair loss (FPHL), including topical minoxidil, topical 17α-estradiol, oral anti-androgen agents, and mineral supplements. Compared with these single agent regimens, combination therapies could be a better therapeutic option in expectation of superior treatment outcome. This study was designed to determine the efficacy of a combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil in Korean patients with FPHL. Therapeutic efficacy was evaluated in 34 women who applied topical 0.025% 17α-estradiol and 3% minoxidil once daily for more than 6 months. Phototrichogram analysis was performed before and after therapy. The efficacy was evaluated with respect to total hair count, hair caliber (as assessed by phototrichogram analysis), and photographic assessment. Total hair count and hair caliber both increased from baseline to 6 months in patients treated with the combination therapy of topical 0.025% 17α-estradiol and 3% minoxidil ( p <0.001). Photographic assessment also revealed significant disease improvement, thus supporting the therapeutic efficacy. A combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil can be tried as an effective treatment for FPHL.

Estradiol impairs the antiproliferative and proapoptotic effect of Zoledronic acid in hormone sensitive breast cancer cells in vitro

PubMed Central

Weingartshofer, Sigrid; Grunt, Thomas W.; Mairhofer, Mario; Tan, Yen; Gamper, Jutta; Singer, Christian F.

2017-01-01

Background Zoledronic acid (ZA) has antiresorptive effects and protects from bone metastasis in women with early breast cancer. In addition, in postmenopausal women with endocrine responsive breast cancer ZA prolongs DFS. The exact mechanism is still unclear. We have therefore investigated the effect of increasing concentrations of ZA in breast cancer cell lines in the absence or presence of estradiol to mimic the hormonal environment in vitro. Materials and methods Using assays for cell proliferation (EZ4U, BrdU) and cell death (Annexin/PI), we have analyzed the dose-dependent antiproliferative and pro-apoptotic effects of ZA in two hormone sensitive cell lines (MCF-7 and T47D) and a hormone insensitive, triple negative cell line (MDA-MB-231) in the presence of 0, 1 and 10 nM estradiol. Results In the absence of estradiol, ZA exerts dose-dependent antiproliferative and pro-apoptotic antitumor effects in both, hormone sensitive (MCF-7, T47D) and -insensitive (MDA-MB-231) breast cancer cell lines (p<0.0001). In the presence of estradiol, the antitumoral effect of ZA was significantly decreased only in the hormone sensitive MCF-7 and T47D cell lines (p = 0.0008 and p = 0.0008, respectively). Conclusion We have demonstrated that estradiol impairs the antiproliferative and proapoptotic effect of ZA in hormone sensitive, but not in hormone insensitive breast cancer cell lines. Our findings provide a possible explanation for the differential effect of ZA on DFS in pre- and postmenopausal patients with hormone sensitive early breast cancer, which has been demonstrated clinically. We further hypothesize that endocrine insensitive tumors such as triple negative breast cancer (TNBC) should benefit from ZA irrespective of their menopausal status. PMID:28945801

Coronaridine congeners inhibit human α3β4 nicotinic acetylcholine receptors by interacting with luminal and non-luminal sites.

PubMed

Arias, Hugo R; Targowska-Duda, Katarzyna M; Feuerbach, Dominik; Jozwiak, Krzysztof

2015-08-01

To characterize the interaction of coronaridine congeners with human (h) α3β4 nicotinic acetylcholine receptors (AChRs), structural and functional approaches were used. The Ca(2+) influx results established that coronaridine congeners noncompetitively inhibit hα3β4 AChRs with the following potency (IC50's in μM) sequence: (-)-ibogamine (0.62±0.23)∼(+)-catharanthine (0.68±0.10)>(-)-ibogaine (0.95±0.10)>(±)-18-methoxycoronaridine [(±)-18-MC] (1.47±0.21)>(-)-voacangine (2.28±0.33)>(±)-18-methylaminocoronaridine (2.62±0.57 μM)∼(±)-18-hydroxycoronaridine (2.81±0.54)>(-)-noribogaine (6.82±0.78). A good linear correlation (r(2)=0.771) between the calculated IC50 values and their polar surface area was found, suggesting that this is an important structural feature for its activity. The radioligand competition results indicate that (±)-18-MC and (-)-ibogaine partially inhibit [(3)H]imipramine binding by an allosteric mechanism. Molecular docking, molecular dynamics, and in silico mutation results suggest that protonated (-)-18-MC binds to luminal [i.e., β4-Phe255 (phenylalanine/valine ring; position 13'), and α3-Leu250 and β4-Leu251 (leucine ring; position 9')], non-luminal, and intersubunit sites. The pharmacophore model suggests that nitrogens from the ibogamine core as well as methylamino, hydroxyl, and methoxyl moieties at position 18 form hydrogen bonds. Collectively our data indicate that coronaridine congeners inhibit hα3β4 AChRs by blocking the ion channel's lumen and probably by additional negative allosteric mechanisms by interacting with a series of non-luminal sites. Copyright © 2015 Elsevier Ltd. All rights reserved.

17β-Estradiol Induced Effects on Anterior Cruciate Ligament Laxness and Neuromuscular Activation Patterns in Female Runners.

PubMed

Khowailed, Iman Akef; Petrofsky, Jerrold; Lohman, Everett; Daher, Noha; Mohamed, Olfat

2015-08-01

We investigate the effects of 17β-Estradiol across phases of menstrual cycle on the laxness of the anterior cruciate ligament (ACL) and the neuromuscular control patterns around the knee joint in female runners. Twelve healthy female runners who reported normal menstrual cycles for the previous 6 months were tested twice across one complete menstrual cycle for serum levels of 17β-estradiol, and knee joint laxity (KJL). Electromyographic (EMG) activity of the quadriceps and hamstrings muscles was also recorded during running on a treadmill. The changes in the EMG activity, KJL, and hormonal concentrations were recorded for each subject during the follicular and the ovulatory phases across the menstrual cycle. An observed increase in KJL in response to peak estradiol during the ovulatory phase was associated with increased preactivity of the hamstring muscle before foot impact (p<0.001). A consistent pattern was also observed in the firing of the quadriceps muscle recruitment pattern throughout the follicular phase associated with decreased hamstring recruitment pattern during weight acceptance phase of running (p=0.02). Additionally, a low ratio of medial to lateral quadriceps recruitment was associated with a significant reduction of the quadriceps to hamstring co-contraction ratio during the follicular phase. Changes in KJL during the menstrual cycle in response to 17β-estradiol fluctuations changes the neuromuscular control around the knee during running. Female runners utilize different neuromuscular control strategies during different phases of the menstrual cycle, which may contribute to increased ACL injury risk.

Interaction of estradiol and high density lipoproteins on proliferation of the human breast cancer cell line MCF-7 adapted to grow in serum free conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jozan, S.; Faye, J.C.; Tournier, J.F.

1985-11-27

The responsiveness of the human mammary carcinoma cell line MCF-7 to estradiol and tamoxifen treatment has been studied in different culture conditions. Cells from exponentially growing cultures were compared with cells in their initial cycles after replating from confluent cultures (''confluent-log'' cells). It has been observed that estradiol stimulation of tritiated thymidine incorporation decreases with cell density and that ''confluent-log'' cells are estrogen unresponsive for a period of four cell cycles in serum-free medium conditions. On the other hand, growth of cells replated from exponentially growing, as well as from confluent cultures, can be inhibited by tamoxifen or a combinedmore » treatment with tamoxifen and the progestin levonorgestrel. This growth inhibitory effect can be rescued by estradiol when cells are replated from exponentially growing cultures. The growth inhibitory effect cannot be rescued by estradiol alone (10(-10) to 10(-8) M) when cells are replated from confluent cultures. In this condition, the addition of steroid depleted serum is necessary to reverse the state of estradiol unresponsiveness. Serum can be replaced by high density lipoproteins but not by low density lipoproteins or lipoprotein deficient serum. The present data show that estradiol and HDL interact in the control of MCF-7 cell proliferation.« less

Time-trends and congener profiles of PBDEs and PCBs in California peregrine falcons (Falco peregrinus).

PubMed

Park, June-Soo; Holden, Arthur; Chu, Vivian; Kim, Michele; Rhee, Alexandra; Patel, Puja; Shi, Yating; Linthicum, Janet; Walton, Brian J; McKeown, Karen; Jewell, Nicholas P; Hooper, Kim

2009-12-01

High levels (microg/g lw) of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were measured in peregrine falcon eggs from California (n = 90 eggs from 52 birds, 38 nest sites, collected 1986-2007, SigmaPBDEs median = 4.53, range = 0.08-53.1). Over the past 22 years, PBDE levels more than tripled each decade in the eggs, whereas PCB levels had no significant changes. PBDE levels were highest in eggs from major California cities ("Big Cities"), whereas PCBs showed no difference across the regions. For PBDEs, Big City eggs had markedly different patterns from Coastal eggs: BDE-209 and the higher brominated PBDEs (hexa-nona) were dominant congeners in Big City eggs, while BDE-47 and -99 were dominant in Coastal eggs. In many of the birds that gave multiple eggs over time ("time series"), PBDE patterns changed over time: the high proportions of BDE-209 and higher brominated PBDEs (short half-lives) in young birds contrasted with increasingly higher proportions of BDE-153 (long half-life) and other lower brominated PBDEs as the birds aged. These data are consistent with metabolic debromination of BDE-209 (t(1/2) = 1-2 weeks) to the lower brominated PBDEs, with accumulation over time of BDE-153 (t(1/2) = 3-4 years). In contrast, PCB patterns showed no differences by locations, and did not change over time. Diet (prey birds) may explain the urban PBDE pattern, as the patterns in urban pigeons and peregrines were similar, with high proportions of BDE-209 and the higher-brominated PBDEs. Also, our prey data (feathers from peregrine nests) showed urban peregrines having a higher proportion (>2 fold) of granivorous/opportunistic birds (e.g., "introduced feral" pigeons, mourning doves, starlings) in their diet than coastal peregrines. In summary, these data indicate that BDE-209 exits consumer products as an environmental contaminant to be taken up by wildlife (particularly in urban locations), and undergoes metabolic debromination to the banned lower

Increased egg estradiol concentration feminizes digit ratios of male pheasants (Phasianus colchicus)

NASA Astrophysics Data System (ADS)

Saino, N.; Rubolini, D.; Romano, M.; Boncoraglio, G.

2007-03-01

The length ratio between individual digits differs between males and females in humans, other mammals, lizards, and one bird species. Sexual dimorphism in digit ratios and variation among individuals of the same sex may depend on differential exposure to androgens and estrogens during embryonic life. Organizational effects of sex hormones could cause the observed correlations between digit ratios and diverse phenotypic traits in humans. However, no study has investigated experimentally the effect of prenatal estrogens on digit ratios. We analyzed the effect of estradiol injection in ring-necked pheasant (Phasianus colchicus) eggs on digit ratios. Males from control eggs had higher ratios between the second or third and the fourth digit of the right foot compared to females. Estradiol-treated eggs produced males with lower (feminized) right foot second to fourth digit ratio. Thus, we provided the first experimental evidence that prenatal exposure to physiologically high estrogen levels affects bird digit ratios.

Divergent effects of estradiol and the estrogen receptor-alpha agonist PPT on eating and activation of PVN CRH neurons in ovariectomized rats and mice.

PubMed

Thammacharoen, Sumpun; Geary, Nori; Lutz, Thomas A; Ogawa, Sonoko; Asarian, Lori

2009-05-01

Eating is modulated by estradiol in females of many species and in women. To further investigate the estrogen receptor mechanism mediating this effect, ovariectomized rats and mice were treated with estradiol benzoate or the estrogen receptor-alpha (ER-alpha)-selective agonist PPT. PPT inhibited eating in rats much more rapidly than estradiol (approximately 2-6 h versus >24 h). In contrast, the latencies to vaginal estrus after PPT and estradiol were similar (>24 h). PPT also inhibited eating within a few hours in wild-type mice, but failed to inhibit eating in transgenic mice deficient in ER-alpha (ERalphaKO mice). PPT, but not estradiol, induced the expression of c-Fos in corticotrophin-releasing hormone (CRH)-expressing cells of the paraventricular nucleus (PVN) of the hypothalamus within 90-180 min in rats. Both PPT and estradiol reduced c-Fos expression in an ER-alpha-containing area of the nucleus of the solitary tract. The anomalously rapid eating-inhibitory effect of PPT suggests that PPT's neuropharmacological effect differs from estradiol's, perhaps because PPT differentially activates membrane versus nuclear ER-alpha or because PPT activates non-ER-alpha membrane estrogen receptors in addition to ER-alpha. The failure of PPT to inhibit eating in ERalphaKO mice, however, indicates that ER-alpha is necessary for PPT's eating-inhibitory action and that any PPT-induced activation of non-ER-alpha estrogen receptors is not sufficient to inhibit eating. Finally, the rapid induction of c-Fos in CRH-expressing cells in the PVN by PPT suggests that PPT elicits a neural response that is similar to that elicited by stress or aversive emotional stimuli.

Treatment of acne using a 3-milligram drospirenone/20-microgram ethinyl estradiol oral contraceptive administered in a 24/4 regimen: a randomized controlled trial.

PubMed

Maloney, J Michael; Dietze, Peter; Watson, David; Niknian, Minoo; Lee-Rugh, Sooji; Sampson-Landers, Carole; Korner, Paul

2008-10-01

To assess the efficacy of the combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol (3-mg drospirenone/20-microgram ethinyl estradiol) administered as 24 consecutive days of active treatment after a 4-day hormone-free interval (24/4 regimen) compared with placebo for the treatment of moderate acne vulgaris. Healthy females aged 14-45 years with moderate acne were randomized in this double-blind study to 3-mg drospirenone/20-microgram ethinyl estradiol (n=270) or placebo (n=268) for six cycles of 28 days. The primary outcome measures of acne lesion counts and Investigator Static Global Assessment scale ratings were assessed at baseline and during cycles 1, 3, and 6. The percentage reduction from baseline to endpoint for total lesions is 46.3% for 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 combination oral contraceptive group and 30.6% for placebo group (P<.001). The likelihood of participants in the 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen group having "clear" or "almost clear" skin as rated by the investigators at endpoint was about threefold (odds ratio 3.13, 95% confidence interval 1.69-5.81; P=.001) greater than in the placebo group. The 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen was well tolerated. The low-dose combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol administered in a 24/4 regimen significantly reduced acne lesion counts more effectively than placebo and demonstrated greater improvement in the Investigator Static Global Assessment rating of acne. The safety profile was consistent with low-dose combined oral contraceptive use.

Adenosine Amine Congener as a Cochlear Rescue Agent

PubMed Central

Vlajkovic, Srdjan M.; Chang, Hao; Paek, Song Yee; Chi, Howard H.-T.; Sreebhavan, Sreevalsan; Telang, Ravindra S.; Tingle, Malcolm; Housley, Gary D.; Thorne, Peter R.

2014-01-01

We have previously shown that adenosine amine congener (ADAC), a selective A1 adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment. Methods. ADAC (25–300 μg/kg) was administered intraperitoneally to Wistar rats (8–10 weeks old) at intervals (6–72 hours) after exposure to traumatic noise (8–16 kHz, 110 dB sound pressure level, 2 hours). Hearing sensitivity was assessed using auditory brainstem responses (ABR) before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous) administration. Results. ADAC was most effective in the first 24 hours after noise exposure at doses >50 μg/kg, providing up to 21 dB protection (averaged across 8–28 kHz). Pharmacokinetic studies demonstrated a short (5 min) half-life of ADAC in plasma after intravenous administration without detection of degradation products. Conclusion. Our data show that ADAC mitigates noise-induced hearing loss in a dose- and time-dependent manner, but further studies are required to establish its translation as a clinical otological treatment. PMID:25243188

Congener-specific distribution and bioaccumulation of short-chain chlorinated paraffins in sediments and bivalves of the Bohai Sea, China.

PubMed

Ma, Xindong; Chen, Chen; Zhang, Haijun; Gao, Yuan; Wang, Zhen; Yao, Ziwei; Chen, Jiping; Chen, Jingwen

2014-02-15

Short-chain chlorinated paraffins (SCCPs) are a new type of persistent organic pollutants that are of great environmental concern because of their wide distribution. In this study, surface sediments and bivalve samples were collected from the coastal area of the Bohai Sea in China. Total SCCP (ΣSCCP) concentrations in surface sediments and bivalves ranged from 97.4 ng g(-1) dry weight (dw) to 1756.7 ng g(-1) dw and 476.4-3269.5 ng g(-1) dw, respectively. C10-CPs and C11-CPs were the predominant homologue groups in all sediments and bivalves. Specific congener composition analysis and correspondence analysis indicated that the local SCCP source mainly came from CP-42 and CP-52 products, and riverine input had an important function. The biota-sediment accumulation factors of ΣSCCPs for bivalves ranged from 1.08 to 1.61, and a significant correlation indicated that the SCCP congener with higher chlorination degree was more likely to be accumulated in bivalves. Copyright © 2014. Published by Elsevier Ltd.

Sufficient progesterone-priming prior to estradiol stimulation is required for optimal induction of the cervical prostaglandin system in pregnant sheep at 0.7 gestations.

PubMed

Wu, Wen Xuan; Coksaygan, Turhan; Chakrabarty, Kaushik; Collins, Valta; Rose, James C; Nathanielsz, Peter W

2005-08-01

The purposes of this study were to determine the separate and interactive functions of progesterone and estradiol in regulating the cervical prostaglandin (PG) system in pregnant sheep at 0.7 gestations. At 106-108 days of gestational age (dGA), ewes were treated with vehicle for 14 days (n = 5) or vehicle for 12 days followed by estradiol 5 mg twice a day, intramuscularly for 2 days (n = 5) or progesterone 100 mg, twice a day, intramuscularly for 14 days (n = 5) or progesterone 100 mg twice a day, intramuscularly for 10 days and then 2 days vehicle followed by estradiol 5 mg twice a day intramuscularly for 2 days (n = 5). At 121-123 dGA, cervical tissues were obtained under halothane anesthesia. Cervical RNA and protein were extracted and analyzed for prostaglandin-endoperoxide synthase 2 (COX2), two PGE(2) receptors, PTGER2 and PTGER4, and estrogen receptor alpha (ESR1) by Northern and Western blot analysis. Immunocytochemistry and in situ hybridization were applied to localize cellular distribution of COX2, PTGER2, and PTGER4 in the cervix. Data were analyzed by ANOVA. COX2 and PTGER4 mRNAs and proteins were increased (P < 0.05) in ewes treated with combined estradiol and progesterone but not in ewes treated with estradiol or progesterone alone compared with controls. ESR1 mRNA was increased in ewes treated with progesterone and estradiol plus progesterone. In contrast, PTGER2 mRNA and protein remained the same after all treatments. COX2 mRNA and protein were localized only in cervical glandular epithelial cells, whereas PTGER2 and PTGER4 were localized in both cervical glandular epithelial and smooth muscle cells. In conclusion, these data suggest that additional progesterone priming at 0.7 gestations synergizes with estradiol to induce cervical COX2, PTGER4, and ESR1 and support our hypothesis that stimulation of the cervical PG system by estradiol is optimized by sufficient progesterone priming in the pregnant sheep cervix.

Estradiol and luteinizing hormone regulate recognition memory following subchronic phencyclidine: Evidence for hippocampal GABA action.

PubMed

Riordan, Alexander J; Schaler, Ari W; Fried, Jenny; Paine, Tracie A; Thornton, Janice E

2018-05-01

The cognitive symptoms of schizophrenia are poorly understood and difficult to treat. Estrogens may mitigate these symptoms via unknown mechanisms. To examine these mechanisms, we tested whether increasing estradiol (E) or decreasing luteinizing hormone (LH) could mitigate short-term episodic memory loss in a phencyclidine (PCP) model of schizophrenia. We then assessed whether changes in cortical or hippocampal GABA may underlie these effects. Female rats were ovariectomized and injected subchronically with PCP. To modulate E and LH, animals received estradiol capsules or Antide injections. Short-term episodic memory was assessed using the novel object recognition task (NORT). Brain expression of GAD67 was analyzed via western blot, and parvalbumin-containing cells were counted using immunohistochemistry. Some rats received hippocampal infusions of a GABA A agonist, GABA A antagonist, or GAD inhibitor before behavioral testing. We found that PCP reduced hippocampal GAD67 and abolished recognition memory. Antide restored hippocampal GAD67 and rescued recognition memory in PCP-treated animals. Estradiol prevented PCP's amnesic effect in NORT but failed to restore hippocampal GAD67. PCP did not cause significant differences in number of parvalbumin-expressing cells or cortical expression of GAD67. Hippocampal infusions of a GABA A agonist restored recognition memory in PCP-treated rats. Blocking hippocampal GAD or GABA A receptors in ovx animals reproduced recognition memory loss similar to PCP and inhibited estradiol's protection of recognition memory in PCP-treated animals. In summary, decreasing LH or increasing E can lessen short-term episodic memory loss, as measured by novel object recognition, in a PCP model of schizophrenia. Alterations in hippocampal GABA may contribute to both PCP's effects on recognition memory and the hormones' ability to prevent or reverse them. Copyright © 2018 Elsevier Ltd. All rights reserved.

Night shift work and other determinants of estradiol, testosterone, and dehydroepiandrosterone sulfate among middle-aged nurses and midwives.

PubMed

Peplonska, Beata; Bukowska, Agnieszka; Lie, Jenny Anne; Gromadzinska, Jolanta; Zienolddiny, Shanbeh

2016-09-01

The aims of our study were to (i) investigate the association between rotating night shift work and blood concentrations of estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) and (2) evaluate the role of their non-occupational determinants. A cross-sectional study was conducted on 345 premenopausal and 187 postmenopausal nurses and midwives (263 women working rotating night shifts and 269 women working during days). Data from in-person interviews were used, anthropometric measurements were performed, and body mass index (BMI) and waist- to-hip ratio were calculated. Morning blood and spot urine samples were collected. Multiple linear regression models were fitted with hormone concentrations as dependent variables, and night shift work characteristics and demographic, reproductive, lifestyle and anthropometric determinants as independent variables. Modification of the effect by chronotype was examined. Among postmenopausal women, we observed a statistically significant positive association between the total duration of night shift work >15 years and estradiol level (P<0.05 when compared to night work duration <5 years). Night shift work characteristics were significantly associated with estradiol among morning-type postmenopausal women. The well-established associations between hormones and their major determinants, such as age and BMI, were confirmed. The findings of our study imply that prolonged night shift work may be associated with increased estradiol levels among postmenopausal women, especially among the morning-type postmenopausal women.

Efficacy of a new oral contraceptive containing drospirenone and ethinyl estradiol in the long-term treatment of hirsutism.

PubMed

Batukan, Cem; Muderris, Iptisam Ipek

2006-02-01

This study represents long term clinical and biochemical results and the response of different body parts to medical therapy with oral ethinyl estradiol/drospirenone combination in hirsute patients with or without polycystic ovary syndrome (PCOS). Prospective, open, controlled clinical study. Outpatients at Erciyes University Medical School. Fifty women with moderate to severe hirsutism were recruited. Two women were lost to follow-up. Women were treated with 3 mg of drospirenone and 30 microg of ethinyl estradiol for 12 cycles. Hirsutism was assessed at 6-month intervals using the Ferriman-Gallwey (F-G) scoring system. Serum FSH, LH, total and free testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), estradiol (E2), and sex-hormone binding globulin (SHBG) levels at 6 and 12 months of therapy were compared with baseline values. Total mean FG score declined by 67% and 78% after 6 and 12 months, respectively. Improvement was most prominent on the chest and abdomen, followed by the upper lip and chin. The lowest effect was observed on the back and arms. Serum levels of total and free T and A decreased, whereas SHBG levels increased significantly after 6 and 12 months when compared with baseline levels. Drospirenone/ethinyl estradiol combination exerts significant antiandrogenic activity and is effective in improving facial hirsutism. The beneficial effect is most obvious after six cycles and continues thereafter at a slower rate.

The new extended-cycle levonorgestrel-ethinyl estradiol oral contraceptives.

PubMed

Bonnema, Rachel A; Spencer, Abby L

2011-09-19

Effective contraceptive counseling requires an understanding of a woman's preferences and medical history as well as the risks, benefits, side effects, and contraindications of each contraceptive method. Hormonal contraceptives using a variety of delivery methods are highly effective and this review highlights the new extended-cycle levonorgestrel-ethinyl estradiol contraceptives. Extended-cycle OCPs are unique in offering fewer or no withdrawal bleeds over the course of one year but providers need to carefully counsel women regarding the initial increased breakthrough bleeding. Extended-cycle OCPs may be of particular benefit in women with medical comorbidities who would benefit from less withdrawal bleeds, those desiring to avoid monthly menses due to increased hormonal withdrawal symptoms, or simply women who don't desire a monthly period. The risks associated with all extended-cycle OCPs have been found to be similar to those of traditional OCPs therefore counseling on the risks and side effects is comparable to that of any combined hormonal contraceptives. Newer extended-cycle regimens shorten or eliminate the hormone-free interval, decrease frequency of menses to four times per year or eliminate menses altogether. This can reduce the risk of common menstrual symptoms, endometriosis, or severe dysmenorrhea by offering potentially greater ovarian suppression and preventing endogenous estradiol production while still providing highly effective, rapidly reversible, and safe contraception.

Biomagnification of higher brominated PBDE congeners in an urban terrestrial food web in north China based on field observation of prey deliveries.

PubMed

Yu, Le-Huan; Luo, Xiao-Jun; Wu, Jiang-Ping; Liu, Li-Yu; Song, Jie; Sun, Quan-Hui; Zhang, Xiu-Lan; Chen, Da; Mai, Bi-Xian

2011-06-15

As an important group of brominated flame retardants, polybrominated diphenyl ethers (PBDEs) persist in the wildlife food webs. However, the biomagnification of PBDEs has not been adequately studied in the terrestrial food webs. In this study, a terrestrial food web composed of common kestrels, sparrows, rats, grasshoppers, and dragonflies in the urban environment from northern China was obtained. A field prey delivery study, reinforced by δ¹³C and δ¹⁵N analyses, indicates that sparrows are the primary prey items of common kestrels. Concentrations of PBDEs were in the following order: common kestrel > sparrow > rat > grasshopper and dragonfly with BDE-209 as the dominant congener. Biomagnification factors (BMFs) were calculated as the ratio between the lipid normalized concentrations in the predator and prey. The highest BMF (6.9) was determined for BDE-153 in sparrow/common kestrel food chain. Other higher brominated congeners, such as BDE-202, -203, -154, -183, -197, and -209, were also biomagnified in this terrestrial food chain with BMF of 1.3-4.7. BDE-47, -99, and -100 were found to be biodiluted from sparrow to common kestrel (BMFs < 1). Measured BMF values for BDE-153, -47, -99, and -100 were consistent with predicted values from a nonsteady-state model in American kestrels from another study. Retention factors and metabolism of BDE congeners may be confounding factors influencing the measured BMFs in this current study.

The effect of a rise or fall of serum estradiol the day before oocyte retrieval in women aged 40-42 with diminished egg reserve.

PubMed

Check, J H; Amui, J; Choe, J K; Cohen, R

2015-01-01

To determine the effect of a drop in serum estradiol the day after injection of human chorionic gonadotropin (hCG) in in vitro fertilization-embryo transfer (IVF-ET) cycles in women aged 40-42 with diminished oocyte reserve. Retrospective study with further requirement that the female partner had a day 3 serum follicle stimulating hormone (FSH) of ≥ 12 miU/mL and ≥ five antral follicles. A drop in serum estradiol the day after hCG injection is not associated with a lower chance of pregnancy compared to those women whose serum estradiol increases. However, their chances of releasing the oocyte before retrieval is significantly higher. A drop in serum estradiol in women of advanced reproductive age with diminished oocyte reserve should not signal the need to cancel the retrieval.

Lack of support for relation between woman's masculinity preference, estradiol level and mating context.

PubMed

Marcinkowska, Urszula M; Ellison, Peter T; Galbarczyk, Andrzej; Milkowska, Karolina; Pawlowski, Boguslaw; Thune, Inger; Jasienska, Grazyna

2016-02-01

It has been proposed that women's preferences for male facial sexual dimorphism are positively correlated with conception probability and differ between short- and long-term mating contexts. In this study, we tested this assumption by analyzing relationships between estradiol levels to the women's preferences of male faces that were manipulated to vary in masculinity. Estradiol was measured in daily saliva samples throughout the entire menstrual cycle collected by Polish women with regular menstrual cycles. In our analyses, we included the three most commonly used definitions of the fertile window in the literature. After computing the overall masculinity preference of each participant and measuring hormone levels, we found that i) the timing of ovulation varied greatly among women (between -11 and -17days from the onset of the next menses, counting backwards), ii) there was no relationship between daily, measured during the day of the test (N=83) or average for the cycle (N=115) estradiol levels and masculinity preferences, iii) there were no differences in masculinity preferences between women in low- and high-conception probability phases of the cycle, and iv) there were no differences in masculinity preferences between short- and long-term mating contexts. Our results do not support the idea that women's preferences for a potential sexual partner's facial masculinity fluctuate throughout the cycle. Copyright © 2015 Elsevier Inc. All rights reserved.

Estradiol modulates functional brain organization during the menstrual cycle: an analysis of interhemispheric inhibition.

PubMed

Weis, Susanne; Hausmann, Markus; Stoffers, Barbara; Vohn, René; Kellermann, Thilo; Sturm, Walter

2008-12-10

According to the hypothesis of progesterone-mediated interhemispheric decoupling (Hausmann and Güntürkün, 2000), functional cerebral asymmetries (FCAs), which are stable in men and change during the menstrual cycle in women, are generated by interhemispheric inhibition of the dominant on the nondominant hemisphere. The change of lateralization during the menstrual cycle in women might indicate that sex hormones play an important role in modulating FCAs. We used functional magnetic resonance imaging to examine the role of estradiol in determining cyclic changes of interhemispheric inhibition. Women performed a word-matching task, while they were scanned twice during the cycle, once during the menstrual and once during the follicular phase. By use of a connectivity analysis we found that the inhibitory influence of left-hemispheric language areas on homotopic areas of the right hemisphere is strongest during the menses, resulting in a pronounced lateralization. During the follicular phase, due to rising estradiol levels, inhibition and thus functional cerebral asymmetries are reduced. These results reveal a powerful neuromodulatory action of estradiol on the dynamics of functional brain organization in the female brain. They may further contribute to the ongoing discussion of sex differences in brain function in that they help explain the dynamic part of functional brain organization in which the female differs from the male brain.

Exogenous application of estradiol to eggs unexpectedly induces male development in two turtle species with temperature-dependent sex determination.

PubMed

Warner, Daniel A; Addis, Elizabeth; Du, Wei-guo; Wibbels, Thane; Janzen, Fredric J

2014-09-15

Steroid hormones affect sex determination in a variety of vertebrates. The feminizing effects of exposure to estradiol and the masculinizing effects of aromatase inhibition during development are well established in a broad range of vertebrate taxa, but paradoxical findings are occasionally reported. Four independent experiments were conducted on two turtle species with temperature-dependent sex determination (Chrysemys picta and Chelydra serpentina) to quantify the effects of egg incubation temperature, estradiol, and an aromatase inhibitor on offspring sex ratios. As expected, the warmer incubation temperatures induced female development and the cooler temperatures produced primarily males. However, application of an aromatase inhibitor had no effect on offspring sex ratios, and exogenous applications of estradiol to eggs produced male offspring across all incubation temperatures. These unexpected results were remarkably consistent across all four experiments and both study species. Elevated concentrations of estradiol could interact with androgen receptors or inhibit aromatase expression, which might result in relatively high testosterone concentrations that lead to testis development. These findings add to a short list of studies that report paradoxical effects of steroid hormones, which addresses the need for a more comprehensive understanding of the role of sex steroids in sexual development. Copyright © 2014 Elsevier Inc. All rights reserved.

The effects on ovarian activity of a monophasic oral contraceptive with 100 microg levonorgestrel and 20 microg ethinyl estradiol.

PubMed

Coney, P; DelConte, A

1999-11-01

An open-label, single-center, noncomparative study was conducted to determine the effects of a monophasic oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol on ovarian activity. The subjects were 26 healthy women 20 to 35 years of age who had normal ovulatory cycles and were not at risk for becoming pregnant. For 3 treatment cycles, they took 1 tablet of active drug daily for 21 days followed by placebo tablets for 7 days. Follicle diameters and serum progesterone and 17beta-estradiol levels were measured before, during, and after treatment. In 2 (2.7%) of 73 cycles, luteinized unruptured follicles were present and in another 2 (2.7%) cycles, ovulation was confirmed by the disappearance of the enlarged follicle. Ovarian activity, as reflected by mean serum progesterone levels, was restored after treatment. The results of this study are in agreement with those of other studies that showed suppression of ovarian activity in women treated with a monophasic oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol. These results indicate that low-dose 100 microg levonorgestrel and 20 microg ethinyl estradiol given for 21 days is effective in suppressing ovarian activity and they confirm the contraceptive efficacy observed in clinical trials (Pearl index of 0.8).

Estradiol regulates expression of miRNAs associated with myogenesis in rainbow trout

USDA-ARS?s Scientific Manuscript database

17-Estradiol (E2) is a steroid hormone that negatively affects muscle growth in rainbow trout, but the mechanism associated with this response is not fully understood. To better characterize the effects of E2 on muscle, we identified differentially regulated microRNAs (miRNAs) and muscle atrophy-rel...

Conversion of estrone to estradiol in male fathead minnows: Implications for assessing risk

EPA Science Inventory

Estrogens are frequently observed in aquatic environments associated with anthropogenic influence, such as agricultural runoff and wastewater treatment effluent. While 17â-estradiol (E2) is the most potent naturally-occurring estrogen, estrone (E1) is often found at higher ...

Local effect of bisphenol A on the estradiol synthesis of ovarian granulosa cells from PCOS.

PubMed

Wang, Yuan; Zhu, Qinling; Dang, Xuan; He, Yaqiong; Li, Xiaoxue; Sun, Yun

2017-01-01

Close relationship between polycystic ovary syndrome (PCOS) and bisphenol A (BPA) has drawn much attention in recent years, while the underlying mechanisms are poorly understood. In our study, we aim to detect BPA concentration in the follicular fluid and investigate its effect on estradiol synthesis in human granulosa cells from PCOS and non-PCOS patients. Follicular fluid and granulosa cells were collected from women who underwent controlled ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection. BPA concentration in the follicular fluid from PCOS patients (440.50 ± 63.70 pg/ml) was significantly higher than that from non-PCOS patients (338.00 ± 57.88 pg/ml). Expression of aromatase and estradiol synthesis in cultured granulosa cells was examined after treatment with BPA from 0.01 to 1 μM for 24 h. Expression of aromatase and estradiol synthesis was downregulated by BPA in a dose-dependent manner in PCOS, but no effect was observed in granulosa cells from non-PCOS patients. These findings provide evidence that increased BPA concentration in the follicular fluid of PCOS patients may play an important role in its pathogenesis by attenuating the expression of aromatase in granulosa cells.

Fetal Hypothalamus-Pituitary-Adrenal Responses to Estradiol Sulfate

PubMed Central

2011-01-01

Estradiol (E2) is an important modifier of the activity of the fetal hypothalamus-pituitary-adrenal axis. We have reported that estradiol-3-sulfate (E2SO4) circulates in fetal blood in far higher concentrations than E2 and that the fetal brain expresses steroid sulfatase, required for local deconjugation of E2SO4. We performed the present study to test the hypothesis that chronic infusion of E2SO4 chronically increases ACTH and cortisol secretion and that it shortens gestation. Chronically catheterized fetal sheep were treated with E2SO4 intracerebroventricular (n = 5), E2SO4 iv (n = 4), or no steroid infusion (control group, n = 5). Fetuses were subjected to arterial blood sampling every other day until spontaneous birth for plasma hormone analysis. Treatment with E2SO4 attenuated preparturient increases in ACTH secretion near term without affecting the ontogenetic rise in plasma cortisol. Infusion of E2SO4 intracerebroventricularly significantly increased plasma E2, plasma E2SO4, and plasma progesterone and shortened gestation compared with all other groups. These results are consistent with the conclusion that E2SO4: 1) interacts with the hypothalamus-pituitary-adrenal axis primarily by stimulating cortisol secretion and inhibiting ACTH and pro-ACTH secretion by negative feedback; and 2) stimulates the secretion of E2 and E2SO4. We conclude that the endocrine response to E2SO4 in the fetus is not identical with the response to E2. PMID:21952234

Baseline Serum Estradiol and Fracture Reduction During Treatment With Hormone Therapy: The Women’s Health Initiative Randomized Trial

PubMed Central

Cauley, Jane A.; LaCroix, Andrea Z.; Robbins, John A.; Larson, Joseph; Wallace, Robert; Wactawski-Wende, Jean; Chen, Zhao; Bauer, Douglas C.; Cummings, Steven R.; Jackson, Rebecca

2009-01-01

Purpose To test the hypothesis that the reduction in fractures with hormone therapy (HT) is greater in women with lower estradiol levels. Methods We conducted a nested case-control study within the Women’s Health Initiative HT Trials. The sample included 231 hip fracture case-control pairs and a random sample of 519 all fracture case-control pairs. Cases and controls were matched for age, ethnicity, randomization date, fracture history and hysterectomy status. Hormones were measured prior to randomization. Incident cases of fracture identified over an average follow-up of 6.53 years. Results There was no evidence that the effect of HT on fracture differed by baseline estradiol (E2) or sex hormone binding globulin (SHBG). Across all quartiles of E2 and SHBG, women randomized to HT had about a 50% lower risk of fracture including hip fracture, compared to placebo. Conclusion The effect of HT on fracture reduction is independent of estradiol and SHBG levels. PMID:19436934

Neonatal exposure to estradiol valerate increases dopamine content in nigrostriatal pathway during adulthood in the rat.

PubMed

Cruz, G; Riquelme, R; Espinosa, P; Jara, P; Dagnino-Subiabre, A; Renard, G M; Sotomayor-Zárate, R

2014-05-01

Research in programming has focused in the study of stimuli that affect sensitive periods of development such as prenatal and neonatal stage. We previously showed that exposure to estradiol valerate to female rats during the first 12 h of life increased catecholamine content in ventromedial-arcuatus hypothalamus of the adult rat. However, changes in others dopaminergic circuits have not been studied. The purpose of this work was to determine the neurotransmitters changes induced by neonatal estradiol valerate (0.1 mg/50 μl s. c. per rat) administration on nigrostriatal pathway of adult female rats. Sesame oil (50 μl s. c. per rat) was administered in a control parallel group. EV-1 adult rats presented effective markers of long-term estrogenization as decreased serum levels of progesterone and a reduction in the size of estrogen-sensitive organs. In the brain, neonatal estradiol valerate administration led to a significant increase in dopamine content in striatum, substantia nigra and ventral tegmental area. With respect to the contents of dopamine metabolites, only 3-methoxytyramine content increased in substantia nigra and ventral tegmental area. In addition, the content of noradrenaline increased only in striatum. Interestingly, estrogenized rats lacked locomotor activity induced by acute dose of amphetamine (1 mg/kg i. p.). Altogether, these results show that neonatal exposure to estradiol valerate permanently modified the content of monoamine neurotransmitters in nigrostriatal pathway and amphetamine-induced locomotor activity of adult female rats. This might imply that estrogenized rats could have changes in the expression of key proteins in dopaminergic regulation, as tyrosine hydroxylase and dopamine transporter. © Georg Thieme Verlag KG Stuttgart · New York.

The Phytoestrogen Genistein Produces Similar Effects as 17β-Estradiol on Anxiety-Like Behavior in Rats at 12 Weeks after Ovariectomy

PubMed Central

Rivadeneyra-Domínguez, Eduardo; Herrera-Huerta, Emma Virginia; Santos-Torres, Andrea

2017-01-01

The phytoestrogen genistein produces anxiolytic-like effects in ovariectomized rats, which highlights its potential therapeutic effect in ameliorating anxiety in surgical menopausal women. However, no studies have directly compared the effects of identical doses of genistein and 17β-estradiol, the main estrogen used in hormone replacement therapy in menopausal women. The present study evaluated the anxiolytic-like effects of identical doses of genistein and 17β-estradiol (0.045, 0.09, and 0.18 mg/kg/7 days, s.c.) in a surgical menopause model in rats in the elevated plus maze and locomotor activity tests at 12 weeks after ovariectomy. Additionally, the participation of estrogen receptor-β in the anxiolytic-like effect of genistein and 17β-estradiol was explored by previous administration of the 5 mg/kg tamoxifen antagonist. Genistein and 17β-estradiol (0.09 and 0.18 mg/kg) similarly reduced anxiety-like behavior in the elevated plus maze and also increased the time spent grooming and rearing, without affecting crossing in locomotor activity test. These effects were blocked by tamoxifen. Present results indicate that the phytoestrogen genistein has a similar behavioral profile as 17β-estradiol in rats at 12 weeks after ovariectomy through action at the estrogen receptor-β. Thus genistein has potential for reducing anxiety-like behavior associated with low concentrations of ovarian hormones, which normally occurs during natural and surgical menopause. PMID:29226152

EFFECTS OF ETHINYL ESTRADIOL ON GONDAL DEVELOPMENT AND PATHOLOGY IN CUNNER, TAUTOGOLABRUS ADSPERSUS

EPA Science Inventory

The intent of this study was to determine histopathologically the effect of ethinyl estradiol (EE2) on gonadal development, liver and kidney condition in reproductively active cunner, Tautogolabrus adspersus. Reproductively active cunner were treated by implanting EE2 in a slow r...

17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes.

PubMed

Catanuto, Paola; Doublier, Sophie; Lupia, Enrico; Fornoni, Alessia; Berho, Mariana; Karl, Michael; Striker, Gary E; Xia, Xiaomei; Elliot, Sharon

2009-06-01

Diabetic nephropathy remains one of the most important causes of end-stage renal disease. This is particularly true for women from racial/ethnic minorities. Although administration of 17beta-estradiol to diabetic animals has been shown to reduce extracellular matrix deposition in glomeruli and mesangial cells, effects on podocytes are lacking. Given that podocyte injury has been implicated as a factor leading to the progression of proteinuria and diabetic nephropathy, we treated db/db mice, a model of type 2 diabetic glomerulosclerosis, with 17beta-estradiol or tamoxifen to determine whether these treatments reduce podocyte injury and decrease glomerulosclerosis. We found that albumin excretion, glomerular volume, and extracellular matrix accumulation were decreased in these mice compared to placebo treatment. Podocytes isolated from all treatment groups were immortalized and these cell lines were found to express the podocyte markers WT-1, nephrin, and the TRPC6 cation channel. Tamoxifen and 17beta-estradiol treatment decreased podocyte transforming growth factor-beta mRNA expression but increased that of the estrogen receptor subtype beta protein. 17beta-estradiol, but not tamoxifen, treatment decreased extracellular-regulated kinase phosphorylation. These data, combined with improved albumin excretion, reduced glomerular size, and decreased matrix accumulation, suggest that both 17beta-estradiol and tamoxifen may protect podocytes against injury and therefore ameliorate diabetic nephropathy.

Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells.

PubMed

Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui

2016-04-19

The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17β-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17β-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17β-estradiol-induced cell proliferation and reversed 17β-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of βKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of βKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of βKlotho in Ishikawa cells abolished 17β-estradiol-induced EMT via inhibiting ERK1/2 signaling. βKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKα signaling inhibitor. In conclusion, metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin.

Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells

PubMed Central

Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui

2016-01-01

The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17β-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17β-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17β-estradiol-induced cell proliferation and reversed 17β-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of βKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of βKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of βKlotho in Ishikawa cells abolished 17β-estradiol-induced EMT via inhibiting ERK1/2 signaling. βKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKα signaling inhibitor. In conclusion, metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin. PMID:26824324

Therapeutic Efficacy of a Combination Therapy of Topical 17α-Estradiol and Topical Minoxidil on Female Pattern Hair Loss: A Noncomparative, Retrospective Evaluation

PubMed Central

Choe, Sung Jay; Lee, Solam; Choi, Jaewoong

2017-01-01

Background A variety of agents have been used to treat female pattern hair loss (FPHL), including topical minoxidil, topical 17α-estradiol, oral anti-androgen agents, and mineral supplements. Compared with these single agent regimens, combination therapies could be a better therapeutic option in expectation of superior treatment outcome. Objective This study was designed to determine the efficacy of a combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil in Korean patients with FPHL. Methods Therapeutic efficacy was evaluated in 34 women who applied topical 0.025% 17α-estradiol and 3% minoxidil once daily for more than 6 months. Phototrichogram analysis was performed before and after therapy. The efficacy was evaluated with respect to total hair count, hair caliber (as assessed by phototrichogram analysis), and photographic assessment. Results Total hair count and hair caliber both increased from baseline to 6 months in patients treated with the combination therapy of topical 0.025% 17α-estradiol and 3% minoxidil (p<0.001). Photographic assessment also revealed significant disease improvement, thus supporting the therapeutic efficacy. Conclusion A combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil can be tried as an effective treatment for FPHL. PMID:28566902

Evaluation of Comprehensive 2-D Gas Chromatography-Time-Of-Flight Mass Spectrometry for 209 Chlorinated Biphenyl Congeners in Two Chromatographic Runs

EPA Science Inventory

This research evaluates a recently developed comprehensive 2-D GC coupled with a time-of-flight (TOF) mass spectrometer for the potential separation of 209 PCB congeners, using a sequence of 1-D and 2-D chromatographic modes. In two consecutive chromatographic runs, using a 40 m,...

Single Targeted Exon Mutation Creates a True Congenic Mouse for Competitive Hematopoietic Stem Cell Transplantation: The C57BL/6-CD45.1(STEM) Mouse.

PubMed

Mercier, Francois E; Sykes, David B; Scadden, David T

2016-06-14

Defining the molecular regulators of hematopoietic stem and progenitor cells (HSPCs) requires in vivo functional analyses. Competitive bone marrow transplants (BMTs) compare control and test HSPCs to demonstrate the functional role of a genetic change or chemical perturbation. Competitive BMT is enabled by antibodies that specifically recognize hematopoietic cells from congenic mouse strains due to variants of the cell surface protein CD45, designated CD45.1 and CD45.2. The current congenic competitor strain, B6.SJL-Ptprc(a) Pepc(b)/BoyJ (CD45.1), has a substantial inherent disadvantage in competition against the C57BL/6 (CD45.2) strain, confounding experimental interpretation. Despite backcrossing, the congenic interval over which the B6.SJL-Ptprc(a) Pepc(b)/BoyJ strain differs is almost 40 Mb encoding ∼300 genes. Here, we demonstrate that a single amino acid change determines the CD45.1 epitope. Further, we report on the single targeted exon mutant (STEM) mouse strain, CD45.1(STEM), which is functionally equivalent to CD45.2 cells in competitive BMT. This strain will permit the precise definition of functional roles for candidate genes using in vivo HSPC assays. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Can Measurement of Progesterone, Estradiol, and Prolactin by Immunoassay be Interchanged? A Comparison of the Roche Cobas e601 vs. Abbott Architect i2000sr.

PubMed

Yin, Lianli; Chen, Xiang; Tang, Yinghua; Sun, Yifan

2017-03-01

Progesterone is a reliable indicator of either natural or induced ovulation, and it plays an important role in preparing for implantation in the uterus and maintaining pregnancy. Estradiol is the most powerful natural estrogen in humans. It adjusts reproductive function in females and, with progesterone, maintains a pregnancy. Prolactin is also an important indicator, and its major physiological action is the initiation and maintenance of lactation in women. Architect i2000sr and Cobas e601 are automated immunoassay systems that are widely used to measure progesterone, estradiol, and prolactin concentrations in the blood. However, there is a dearth of confidence in these methods for comparative research. Therefore, the aim of this study is to investigate the correlation of serum progesterone, estradiol, and prolactin results measured with Architect i2000sr and Cobas e601. Two hundred venous blood samples from routine serum progesterone, estradiol, and prolactin tests were analyzed on the Cobas e601 and the Architect i2000sr in our laboratory within the same day. Passing-Bablok regression analysis and a Bland-Altman plot were used to compare methods. According to the concordance correlation coefficient, the correlation was strong in estradiol, but the correlation of prolactin and progesterone was poor between the two systems. The Bland-Altman plots showed that the measured value of progesterone, estradiol, and prolactin detected by Cobas e601 were about 1.30, 1.24, and 1.10 times higher, respectively, than that measured using Architect i2000sr. The results of progesterone, estradiol, and prolactin of one method should not be directly transferable to the other.

Congeners in sugar cane spirits aged in casks of different woods.

PubMed

Bortoletto, Aline M; Alcarde, André R

2013-08-15

The profile of volatile compounds and aging markers in sugar cane spirits aged for 36 months in casks made of 10 types of wood were studied. The ethanol content, volatile acidity, aldehydes, esters, higher alcohols, and methanol were determined. In addition, gallic, vanilic and syringic acids, siringaldehyde, coniferaldehyde, sinapaldehyde, vanillin, 5-hydroxymethylfurfural and furfural were identified and quantified. The profile of volatile compounds characterised aging in each type of wood. The beverage aged in oak cask achieved the highest contents of maturation-related congeners. The Brazilian woods, similar to oak, were jequitibá rosa and cerejeira, which presented the highest contents of some maturation-related compounds, such as vanillin, vanilic acid, syringaldehyde and sinapaldehyde. Although oak wood conferred more chemical complexity to the beverage, Brazilian woods, singly or complementarily, present potential for spirit characterisation and for improving the quality of sugar cane spirits. Copyright © 2013 Elsevier Ltd. All rights reserved.

Contribution of estradiol levels and hormonal contraceptives to sex differences within the fear network during fear conditioning and extinction.

PubMed

Hwang, Moon Jung; Zsido, Rachel G; Song, Huijin; Pace-Schott, Edward F; Miller, Karen Klahr; Lebron-Milad, Kelimer; Marin, Marie-France; Milad, Mohammed R

2015-11-18

Findings about sex differences in the field of fear conditioning and fear extinction have been mixed. At the psychophysiological level, sex differences emerge only when taking estradiol levels of women into consideration. This suggests that this hormone may also influence sex differences with regards to activations of brain regions involved in fear conditioning and its extinction. Importantly, the neurobiological correlates associated with the use of hormonal oral contraceptives in women have not been fully contrasted against men and against naturally cycling women with different levels of estradiol. In this study, we begin to fill these scientific gaps. We recruited 37 healthy men and 48 healthy women. Of these women, 16 were using oral contraceptives (OC) and 32 were naturally cycling. For these naturally cycling women, a median split was performed on their serum estradiol levels to create a high estradiol (HE) group (n = 16) and a low estradiol (LE) group (n = 16). All participants underwent a 2-day fear conditioning and extinction paradigm in a 3 T MR scanner. Using the 4 groups (men, HE women, LE women, and OC users) and controlling for age and coil type, one-way ANCOVAs were performed to look at significant activations within the nodes of the fear circuit. Using post-hoc analyses, beta-weights were extracted in brain regions showing significant effects in order to unveil the differences based on hormonal status (men, HE, LE, OC). Significant main effect of hormonal status group was found across the different phases of the experiment and in different sub-regions of the insular and cingulate cortices, amygdala, hippocampus, and hypothalamus. During conditioning, extinction and recall, most of the observed differences suggested higher activations among HE women relative to men. During the unconditioned response, however, a different pattern was observed with men showing significantly higher brain activations. Our data further support the important contribution

The congenic normal R/APfd and jaundiced R/APfd-j/j rat strains: a new animal model of hereditary non-haemolytic unconjugated hyperbilirubinaemia due to defective bilirubin conjugation.

PubMed

Leyten, R; Vroemen, J P; Blanckaert, N; Heirwegh, K P

1986-10-01

In this paper the production of the R/APfd-j/j strain which is congenic with the R/APfd strain is reported. The R/APfd-j/j completely lacks hepatic bilirubin UDP-glucuronyltransferase activity, as do our GUNNXR/Pfd-j/j rat strain and various other stocks of GUNN rats (j/j) described in the literature. Our recombinant inbred strain GUNNXR/Pfd-j/j was produced from non-inbred GUNN (j/j) rats. This GUNNXR/Pfd-j/j rat was used as a donor of the jaundice gene j, the R/APfd rat serving as the recipient. After eight backcross-intercross cycles (16 generations) the R/APfd-j/j strain was obtained which is congenic with the R/APfd strain. Congenicity was demonstrated by various techniques including transplantation of skin tissue, strain-specific tumour cells and hepatocytes, the mixed lymphocyte reaction, and comparison of biochemical markers. The potential of the novel inbred strain of jaundiced rat, R/APfd-j/j, and the corresponding control strain R/APfd for biochemical and clinical studies of bilirubin metabolism are briefly discussed.

In Vitro Drug Transfer Due to Drug Retention in Human Epidermis Pretreated with Application of Marketed Estradiol Transdermal Systems.

PubMed

Krishnaiah, Yellela S R; Pavurala, Naresh; Yang, Yang; Manda, Prashanth; Katragadda, Usha; Yang, Yongsheng; Shah, Rakhi; Fang, Guodong; Khan, Mansoor A

2017-08-01

Study objective was to assess skin-to-skin drug transfer potential that may occur due to drug retention in human epidermis (DRE) pretreated with application of estradiol transdermal drug delivery systems (TDDS) and other estradiol transdermal dosage forms (gels and sprays). TDDS (products-A, B, and C) with varying formulation design and composition, and other estradiol transdermal products (gel and spray) were applied to heat separated human epidermis (HSE) and subjected to in vitro drug permeation study. Amounts of DRE were quantified after 24 h. The DRE with product-B was significantly (P < 0.001) higher than that with product-C, product-A, gel, and spray. However, products-A and C, gel, and spray showed almost the same (P > 0.05) amounts of DRE. A separate in vitro permeation study was carried out to determine amounts of drug transferred from drug-retaining epidermis to untreated HSE. The amounts of drug transferred, due to DRE after 8 h, with product-C were significantly (P < 0.001) higher than those with products-A and B, gel, and spray. The in vitro study results indicate a high potential of skin-to-skin drug transfer due to the DRE after labeled period of using estradiol TDDS, though the clinical relevance of these findings is yet to be determined.

Role of 17 beta-estradiol on type IV collagen fibers volumetric density in the basement membrane of bladder wall.

PubMed

de Fraga, Rogerio; Dambros, Miriam; Miyaoka, Ricardo; Riccetto, Cássio Luís Zanettini; Palma, Paulo César Rodrigues

2007-10-01

The authors quantified the type IV collagen fibers volumetric density in the basement membrane of bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old) randomly divided in 4 groups: group 1, remained intact (control); group 2, submitted to bilateral oophorectomy and daily replacement 4 weeks later of 17 beta-estradiol for 12 weeks; group 3, sham operated and daily replacement 4 weeks later of sesame oil for 12 weeks; and group 4, submitted to bilateral oophorectomy and killed after 12 weeks. It was used in immunohistochemistry evaluation using type IV collagen polyclonal antibody to stain the fibers on paraffin rat bladder sections. The M-42 stereological grid system was used to analyze the fibers. Ovariectomy had an increase effect on the volumetric density of the type IV collagen fibers in the basement membrane of rat bladder wall. Estradiol replacement in castrated animals demonstrated a significative difference in the stereological parameters when compared to the castrated group without hormonal replacement. Surgical castration performed on rats induced an increasing volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall and the estradiol treatment had a significant effect in keeping a low volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall.

Systemic delivery of estradiol, but not testosterone or progesterone, alters very low density lipoprotein-triglyceride kinetics in postmenopausal women.

PubMed

Smith, Gordon I; Reeds, Dominic N; Okunade, Adewole L; Patterson, Bruce W; Mittendorfer, Bettina

2014-07-01

Sexual dimorphism in plasma triglyceride (TG) metabolism is well established but it is unclear to what extent it is driven by differences in the sex hormone milieu. RESULTS from previous studies evaluating the effects of sex steroids on plasma TG homeostasis are inconclusive because they relied on orally administered synthetic hormone preparations or evaluated only plasma lipid concentrations but not kinetics. The purpose of this study was to evaluate the effects of systemically delivered 17β-estradiol, progesterone, and T on very low density lipoprotein-triglyceride (VLDL-TG) concentration and kinetics in postmenopausal women. VLDL-TG concentration and kinetics were evaluated by using stable isotope-labeled tracer techniques in four groups of postmenopausal women (n = 27 total) who were studied before and after treatment with either 17β-estradiol (0.1 mg/d via continuous delivery skin patch), progesterone (100 mg/d via vaginal insert) and T (12.5 mg/d via skin gel), or no intervention (control group). VLDL-TG concentration and kinetics were unchanged in the control group and not altered by T and progesterone administration. Estradiol treatment, in contrast, reduced VLDL-TG concentration by approximately 30% due to accelerated VLDL-TG plasma clearance (25.1 ± 2.5 vs. 17.4 ± 2.7 mL/min; P < .01). Estradiol, but not progesterone or T, is a major regulator of VLDL-TG metabolism.

Nasal Bone Shape Is under Complex Epistatic Genetic Control in Mouse Interspecific Recombinant Congenic Strains

PubMed Central

Burgio, Gaétan; Baylac, Michel; Heyer, Evelyne; Montagutelli, Xavier

2012-01-01

Background Genetic determinism of cranial morphology in the mouse is still largely unknown, despite the localization of putative QTLs and the identification of genes associated with Mendelian skull malformations. To approach the dissection of this multigenic control, we have used a set of interspecific recombinant congenic strains (IRCS) produced between C57BL/6 and mice of the distant species Mus spretus (SEG/Pas). Each strain has inherited 1.3% of its genome from SEG/Pas under the form of few, small-sized, chromosomal segments. Results The shape of the nasal bone was studied using outline analysis combined with Fourier descriptors, and differential features were identified between IRCS BcG-66H and C57BL/6. An F2 cross between BcG-66H and C57BL/6 revealed that, out of the three SEG/Pas-derived chromosomal regions present in BcG-66H, two were involved. Segments on chromosomes 1 (∼32 Mb) and 18 (∼13 Mb) showed additive effect on nasal bone shape. The three chromosomal regions present in BcG-66H were isolated in congenic strains to study their individual effect. Epistatic interactions were assessed in bicongenic strains. Conclusions Our results show that, besides a strong individual effect, the QTL on chromosome 1 interacts with genes on chromosomes 13 and 18. This study demonstrates that nasal bone shape is under complex genetic control but can be efficiently dissected in the mouse using appropriate genetic tools and shape descriptors. PMID:22662199

Ethinyl estradiol and levonorgestrel alter cognition and anxiety in rats concurrent with a decrease in tyrosine hydroxylase expression in the locus coeruleus and brain-derived neurotrophic factor expression in the hippocampus.

PubMed

Simone, Jean; Bogue, Elizabeth A; Bhatti, Dionnet L; Day, Laura E; Farr, Nathan A; Grossman, Anna M; Holmes, Philip V

2015-12-01

In the United States, more than ten million women use contraceptive hormones. Ethinyl estradiol and levonorgestrel have been mainstay contraceptive hormones for the last four decades. Surprisingly, there is scant information regarding their action on the central nervous system and behavior. Intact female rats received three weeks of subcutaneous ethinyl estradiol (10 or 30μg/rat/day), levonorgestrel (20 or 60μg/rat/day), a combination of both (10/20μg/rat/day and 30/60μg/rat/day), or vehicle. Subsequently, the rats were tested in three versions of the novel object recognition test to assess learning and memory, and a battery of tests for anxiety-like behavior. Serum estradiol and ovarian weights were measured. All treatment groups exhibited low endogenous 17β-estradiol levels at the time of testing. Dose-dependent effects of drug treatment manifested in both cognitive and anxiety tests. All low dose drugs decreased anxiety-like behavior and impaired performance on novel object recognition. In contrast, the high dose ethinyl estradiol increased anxiety-like behavior and improved performance in cognitive testing. In the cell molecular analyses, low doses of all drugs induced a decrease in tyrosine hydroxylase mRNA and protein in the locus coeruleus. At the same time, low doses of ethinyl estradiol and ethinyl estradiol/levonorgestrel increased galanin protein in this structure. Consistent with the findings above, the low dose treatments of ethinyl estradiol and combination ethinyl estradiol/levonorgestrel reduced brain-derived neurotrophic factor mRNA in the hippocampus. These effects of ethinyl estradiol 10μg alone and in combination with levonorgestrel 20μg suggest a diminution of norepinephrine input into the hippocampus resulting in a decline in learning and memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

Confirmation of the progesterone receptor as an efficient marker of treatment with 17β-estradiol in veal calves.

PubMed

Pezzolato, Marzia; Botta, Mario; Baioni, Elisa; Richelmi, Guia Benedetta; Pitardi, Danilo; Varello, Katia; Caramelli, Maria; Bozzetta, Elena

2016-01-01

Under current European Union legislation the use of anabolic steroids in food-producing livestock is banned because of their long-term adverse effects on human health. We examined the expression profile of the immunohistochemical marker progesterone receptor in veal calves' sex accessory glands following experimental administration of anabolic compounds. The aim was to confirm the accuracy of the immunohistochemical approach in the detection of the over-expression of the progesterone receptor induced by the administration of sexual steroids at low levels (17β-estradiol and nandrolone alone or in combination). A total of 217 male veal calves were randomly divided into four groups: group A (104 calves) treated with 17β-estradiol (5 mg/head; 4 weekly injections); group B (20 calves) treated with nandrolone (50 mg/head; 4 weekly injections); group C (20 calves) treated with the association of the two steroids (5 mg estradiol + 50 mg nandrolone; 4 weekly injections); and group K (73 calves) kept as a control. All the sexual accessory glands were collected at the slaughterhouse (15 days after the last administration) and subjected to immunohistochemical staining with anti-progesterone receptor antibody. All the calves treated with 17β-estradiol alone or in association with nandrolone (groups A and C) showed strong positivity, while nandrolone-treated calves and controls (groups B and K) gave negative results to the immunohistochemical investigation. The statistical analysis showed that the progesterone receptor is a significant predictor of 17β-estradiol treatment alone or in association with nandrolone (p < 0.001): the immunohistochemical study resulted in 100% sensitivity (CI = 95%: 97.1-100%) and specificity (CI = 95%: 95.1-100%) for prostate and 99% sensitivity (CI = 95%: 95.6-100%) and 100% specificity (CI = 95%: 95.1-100%) for bulbo-urethral glands. The data confirm that this innovative biological approach offers a reliable tool to enhance the efficacy of

Transport of estradiol-17β-glucuronide, estrone-3-sulfate and taurocholate across the endoplasmic reticulum membrane: evidence for different transport systems☆

PubMed Central

Wlcek, Katrin; Hofstetter, Lia; Stieger, Bruno

2014-01-01

Important reactions of drug metabolism, including UGT mediated glucuronidation and steroidsulfatase mediated hydrolysis of sulfates, take place in the endoplasmic reticulum (ER) of hepatocytes. Consequently, UGT generated glucuronides, like estradiol-17β-glucuronide, have to be translocated back into the cytoplasm to reach their site of excretion. Also steroidsulfatase substrates, including estrone-3-sulfate, have to cross the ER membrane to reach their site of hydrolysis. Based on their physicochemical properties such compounds are not favored for passive diffusion and therefore likely necessitate transport system(s) to cross the ER membrane in either direction. The current study aims to investigate the transport of taurocholate, estradiol-17β-glucuronide, and estrone-3-sulfate in smooth (SER) and rough (RER) endoplasmic reticulum membrane vesicles isolated from Wistar and TR− rat liver. Time-dependent and bidirectional transport was demonstrated for taurocholate, showing higher uptake rates in SER than RER vesicles. For estradiol-17β-glucuronide a fast time-dependent efflux with similar efficiencies from SER and RER but no clear protein-mediated uptake was shown, indicating an asymmetric transport system for this substrate. Estrone-3-sulfate uptake was time-dependent and higher in SER than in RER vesicles. Inhibition of steroidsulfatase mediated estrone-3-sulfate hydrolysis decreased estrone-3-sulfate uptake but had no effect on taurocholate or estradiol-17β-glucuronide transport. Based on inhibition studies and transport characteristics, three different transport mechanisms are suggested to be involved in the transport of taurocholate, estrone-3-sulfate and estradiol-17β-glucuronide across the ER membrane. PMID:24406246

Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses

PubMed Central

Saal, Frederick S. vom; Timms, Barry G.; Montano, Monica M.; Palanza, Paola; Thayer, Kristina A.; Nagel, Susan C.; Dhar, Minati D.; Ganjam, V. K.; Parmigiani, Stefano; Welshons, Wade V.

1997-01-01

On the basis of results of studies using high doses of estrogens, exposure to estrogen during fetal life is known to inhibit prostate development. However, it is recognized in endocrinology that low concentrations of a hormone can stimulate a tissue, while high concentrations can have the opposite effect. We report here that a 50% increase in free-serum estradiol in male mouse fetuses (released by a maternal Silastic estradiol implant) induced a 40% increase in the number of developing prostatic glands during fetal life; subsequently, in adulthood, the number of prostatic androgen receptors per cell was permanently increased by 2-fold, and the prostate was enlarged by 30% (due to hyperplasia) relative to untreated males. However, as the free serum estradiol concentration in male fetuses was increased from 2- to 8-fold, adult prostate weight decreased relative to males exposed to the 50% increase in estradiol. As a model for fetal exposure to man-made estrogens, pregnant mice were fed diethylstilbestrol (DES) from gestation days 11 to 17. Relative to controls, DES doses of 0.02, 0.2, and 2.0 ng per g of body weight per day increased adult prostate weight, whereas a 200-ng-per-g dose decreased adult prostate weight in male offspring. Our findings suggest that a small increase in estrogen may modulate the action of androgen in regulating prostate differentiation, resulting in a permanent increase in prostatic androgen receptors and prostate size. For both estradiol and DES, prostate weight first increased then decreased with dose, resulting in an inverted-U dose-response relationship. PMID:9050904

Exposure to increased levels of estradiol during development can have long-term effects on the response to undernutrition in female rats.

PubMed

Carrillo, B; Collado, P; Díaz, F; Chowen, J A; Pinos, H

2016-11-01

Undernutrition during development alters the expression of peptides that control energy expenditure and feeding behavior. Estrogens can also modulate these peptides. Here, we analyze whether the early postnatal administration of estradiol modulates the effects of undernutrition on neuroendocrine parameters in adult female Wistar rats. Control rats were fed a control diet. Undernourished pups were submitted to a restricted diet with half of the undernourished rats receiving 0.4 mg/kg s.c. of estradiol benzoate (EB) from postnatal day (P) 6 until P13. Quantitative real-time polymerase chain reaction was performed to determine expression in the hypothalamus of agouti-related peptide (AgRP), proopiomelanocortin (POMC), neuropeptide Y (NPY), and cocaine- and amphetamine-regulated transcript. Plasma estradiol, testosterone, and adiponectin levels were measured by enzyme-linked immunosorbent assay. Total and acylated ghrelin levels were measured in plasma by radioimmunoassay. Insulin and leptin were measured by mulitplex immunoassays. Undernourishment decreased body weight, fat mass, plasma leptin and insulin levels, and hypothalamic POMC mRNA levels. An increase in orexigenic signals AgRP and NPY mRNA levels, and in plasma adiponectin levels were found in undernourished animals. Early postnatal treatment with EB to undernourished female rats reversed the effects of undernutrition on adult hypothalamic POMC mRNA levels. In addition, neonatal EB treatment to undernourished females significantly decreased adult plasma testosterone, estradiol, and acylated ghrelin levels. Our results suggest that increased estradiol during a critical period of development has the capacity to modulate the alterations that undernutrition produces on energy metabolism.

New GLC analysis of urushiol congeners in different plant parts of poison ivy, Toxicodendron radicans.

PubMed

Craig, J C; Waller, C W; Billets, S; Elsohly, M A

1978-04-01

Methods are presented for the direct GLC analysis of the catechol C15 alkenyl side-chain congeners contained in the urushiol fraction of poison ivy (Toxicodendron radicans) and the C17 homologs of poison oak (Toxicodendron diversilobum). A number of liquid phases were investigated and demonstrated varying degrees of separation. The methods developed were applied to the analysis of the urushiol fractions obtained from different plant parts of poison ivy. The effects of extraction before and after drying demonstrated tht a larger percentage of urushiol was obtained when the fresh plant material was extracted with ethanol.

A new comprehensive technique of catheterisation, blood sampling, sample preparation and sample analysis by means of high-pressure liquid chromatography for pharmacokinetic studies with estradiol-linked nitrosoureas and their metabolites.

PubMed

Betsch, B; Berger, M R; Spiegelhalder, B

1990-09-01

Estradiol-linked nitrosoureas are offering new perspectives in the antineoplastic chemotherapy of estradiol-receptor positive mammary carcinomas. In such a molecule estradiol has the function of a carrier which brings about a specific accumulation of the anticancer drug in estradiol-receptor containing tumor cells. However, there is only little knowledge about the pharmacokinetic behavior of this new group of anticancer agents. For that reason a new comprehensive technique of catheterisation, blood sampling, sample preparation and sample analysis with high-pressure liquid chromatography (HPLC) for preclinical pharmacokinetic studies with estradiol-linked nitrosoureas and their metabolites has been developed. N-(2-Chloroethyl)-N-nitroso-carbamoyl-L-alanine-estradiol-17-ester (CNC-alanine-estradiol-17-ester) and N-(2-chloroethyl)-N-nitroso-carbamoyl-L-alanine (CNC-alanine) were used as test compounds. The drugs were tested in female Sprague-Dawley rats with chemically induced mammary carcinomas. The laboratory animals were supplied with two catheters prior to the pharmacokinetic experiments. The blood samples were drawn from the vena cava catheter after the drug had been applied through a vena jugularis catheter. The compounds were extracted from plasma with C18 silicagel reversed phase cartridges. The clean-up technique delivered clear samples only slightly contaminated with the biological matrix. The recovery from plasma was 75 +/- 5% for the hormone-linked CNC-alanine-estradiol-17-ester and 70 +/- 5% for the unlinked CNC-alanine. The analysis was carried out by means of HPLC.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute genistein treatment mimics the effects of estradiol by enhancing place learning and impairing response learning in young adult female rats

PubMed Central

Pisani, Samantha L.; Neese, Steven L.; Doerge, Daniel R.; Helferich, William G.; Schantz, Susan L.; Korol, Donna L.

2012-01-01

Endogenous estrogens have bidirectional effects on learning and memory, enhancing or impairing cognition depending on many variables, including the task and the memory systems that are engaged. Moderate increases in estradiol enhance hippocampus-sensitive place learning, yet impair response learning that taps dorsal striatum function. This memory modulation likely occurs via activation of estrogen receptors, resulting in altered neural function. Supplements containing estrogenic compounds from plants are widely consumed despite limited information about their effects on brain function, including learning and memory. Phytoestrogens can enter the brain and signal through estrogen receptors to affect cognition. Enhancements in spatial memory and impairments in executive function have been found following treatment with soy phytoestrogens, but no tests of actions on striatum-sensitive tasks have been made to date. The present study compared the effects of acute exposure to the isoflavone genistein with the effects of estradiol on performance in place and response learning tasks. Long-Evans rats were ovariectomized, treated with 17β-estradiol benzoate, genistein-containing sucrose pellets, or vehicle (oil or plain sucrose pellets) for two days prior to behavioral training. Compared to vehicle controls, estradiol treatment enhanced place learning at a low (4.5 μg/kg) but not high dose (45 μg/kg), indicating an inverted pattern of spatial memory facilitation. Treatment with 4.4 mg of genistein over two days also significantly enhanced place learning over vehicle controls. For the response task, treatment with estradiol impaired learning at both the low and high doses; likewise, genistein treatment impaired response learning compared to rats receiving vehicle. Overall, genistein was found to mimic estradiol-induced shifts in place and response learning, facilitating hippocampus-sensitive learning and slowing striatum-sensitive learning. These results suggest signaling

Aptamer/Au nanoparticles/cobalt sulfide nanosheets biosensor for 17β-estradiol detection using a guanine-rich complementary DNA sequence for signal amplification.

PubMed

Huang, Ke-Jing; Liu, Yu-Jie; Zhang, Ji-Zong; Cao, Jun-Tao; Liu, Yan-Ming

2015-05-15

We have developed a sensitive sensing platform for 17β-estradiol by combining the aptamer probe and hybridization reaction. In this assay, 2-dimensional cobalt sulfide nanosheet (CoS) was synthesized by a simple hydrothermal method with L-cysteine as sulfur donor. An electrochemical aptamer biosensor was constructed by assembling a thiol group tagged 17β-estradiol aptamer on CoS and gold nanoparticles (AuNPs) modified electrode. Methylene blue was applied as a tracer and a guanine-rich complementary DNA sequence was designed to bind with the unbound 17β-estradiol aptamer for signal amplification. The binding of guanine-rich DNA to the aptamer was inhibited when the aptamer captured 17β-estradiol. Using guanine-rich DNA in the assay greatly amplified the redox signal of methylene blue bound to the detection probe. The CoS/AuNPs film formed on the biosensor surface appeared to be a good conductor for accelerating the electron transfer. The method demonstrated a high sensitivity of detection with the dynamic concentration range spanning from 1.0×10(-9) to 1.0×10(-12) M and a detection limit of 7.0×10(-13) M. Besides, the fabricated biosensor exhibited good selectivity toward 17β-estradiol even when interferents were presented at 100-fold concentrations. Our attempt will extend the application of the CoS nanosheet and this signal amplification assay to biosensing areas. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of sediment particle size on biotransformation of 17β-estradiol and 17β-trenbolone.

PubMed

Zhang, Yun; Sangster, Jodi L; Gauza, Lukasz; Bartelt-Hunt, Shannon L

2016-12-01

Soil/sediment particle size has been reported to influence the sorption and bioavailability of steroid hormones in the environment. However, the impact of particle size on biotransformation has not been well elucidated. The present study investigated the dissipation of 17β-estradiol and 17β-trenbolone and the formation and degradation of the subsequent transformation products in different size fractions of a sandy and a silt loam sediment. The results showed that the decay of 17β-estradiol and 17β-trenbolone associated with fine particles followed a biphasic pattern with more rapid decay in the initial phase followed by a second phase with slower decay of the residues compared to their decay rates in the sand fraction. Estrone and trendione were detected as a primary biotransformation product for 17β-estradiol and 17β-trenbolone, respectively. The parent-to-product conversion ratios and the degradation rates of estrone and trendione varied among different size fractions, but no consistent correlation was observed between decay rates and sediment particle size. Estrone and trendione decayed in the whole sediments at rates not statistically different from those associated with the fine fractions. These results indicate that fine particles may play an important role in influencing the persistence of and the potential risk posed by steroid hormones in the aquatic systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Phenomenological and Spectroscopic Analysis on the Effects of Sediment Ageing and Organic Carbon on the Fate of a PCB Congener Spiked to Sediment

EPA Science Inventory

This study assesses the full cycle transport and fate of a polychlorinated biphenyl (PCB) congener spiked to sediment to empirically and spectroscopically investigate the effects of sediment ageing and organic carbon on the adsorption, desorption, and reaction of the PCB. Caesar ...

Effect of a chronic treatment with 17β-estradiol on striatal dopamine neurotransmission and the Akt/GSK3 signaling pathway in the brain of ovariectomized monkeys.

PubMed

Sánchez, Maria Gabriela; Morissette, Marc; Di Paolo, Thérèse

2012-02-01

The present experiments sought the effect of chronic treatment with 17β-estradiol on striatal dopaminergic activity and the Akt/GSK3 signaling pathway in the brain of monkeys. Eight female monkeys (Macacca fascicularis) were ovariectomized (OVX) and a month later, half received a month treatment with 17β-estradiol and the other with vehicle. The DA transporter (DAT) was measured by autoradiography with [(125)I]RTI-121 and the vesicular DA transporter (VMAT(2)) with [(3)H]TBZ-OH at three rostro-caudal levels (anterior, middle and posterior) of the caudate nucleus and putamen subdivided in their lateral/medial, ventral/dorsal sub-regions. Specific binding to DAT was increased in all sub-regions of the caudate nucleus and the putamen of 17β-estradiol-treated compared to vehicle-treated monkeys whereas specific binding to VMAT(2) remained unchanged. We measured by Western blot the phosphorylated forms of Akt at serine 473 and threonine 308, GSK3β at serine 9 and tyrosine 216 and GSK3α at serine 21 in anterior, middle and posterior caudate nucleus and putamen. 17β-Estradiol treatment increased in all the caudate nucleus and putamen pAkt (Ser473)/βIII-tubulin, pGSK3β (Ser9)/βIII-tubulin and in putamen Akt/βIII-tubulin compared to vehicle-treated monkeys. In anterior and middle putamen, pAkt (Thr308)/βIII-tubulin was also increased in monkeys treated with 17β-estradiol. pGSK3β (Tyr216)/βIII-tubulin and pGSK3α (Ser21)/βIII-tubulin remained unchanged by the 17β-estradiol treatment. These results suggest that 17β-estradiol activates striatal DA neurotransmission in primates as reflected with increased DAT specific binding and downstream activation of Akt/GSK3 signaling. This supports a beneficial role of a chronic treatment with 17β-estradiol by increasing the activity of signaling pathways implicated in cell survival. Copyright © 2011 Elsevier Ltd. All rights reserved.

Long-range atmospheric transport of PAHs, PCBs and PBDEs to the central and eastern Mediterranean and changes of PCB and PBDE congener patterns in summer 2010

NASA Astrophysics Data System (ADS)

Mulder, Marie D.; Heil, Angelika; Kukučka, Petr; Kuta, Jan; Přibylová, Petra; Prokeš, Roman; Lammel, Gerhard

2015-06-01

The central and eastern Mediterranean is a receptor area for persistent organic pollutants (POPs) emitted in western, central and eastern Europe, particularly during summer. Atmospheric concentrations of PCBs, DDXs, PBDEs, penta- and hexachlorobenzene were measured during a ship-borne survey in the summer of 2010. The concentration of PCBs (sum of 7 congeners) was 3.61 (2.08-7.72) pg m-3, of which 6.7% was associated with the particulate phase. The mean concentration of DDT isomers and their metabolites, DDE and DDD, was 2.60 (0.46-7.60) pg m-3 (particulate mass fraction θ = 0.097), of penta- and hexachlorobenzene 0.22 (<0.39-2.80) pg m-3 and 6.29 (2.48-24.16) pg m-3, respectively, and of PBDEs (sum of 8 congeners) 7.31 (2.80-19.89) pg m-3. The air masses studied had been transported mostly across central Europe, some crossing western Europe. The observed changes of PCB congener patterns along transport routes are in agreement with the perception that the reaction with the OH radical is dominating PCB atmospheric lifetime, and indicate an overestimation of the second order gas-phase reaction rate coefficient of PCB153 with OH by structure-activity relationship.

Polychlorinated biphenyl congeners in sediment cores from the Upper Mississippi River

PubMed Central

Martinez, Andres; Schnoebelen, Douglas J.; Hornbuckle, Keri C.

2015-01-01

We determined polychlorinated biphenyls (PCBs) and radionuclide 137Cs in sediment cores from the Upper Mississippi River (UMR) and the Iowa River, Iowa, at their confluence. Vertical distribution of 137Cs indicated negligible mixing in the UMR core, while the Iowa River core showed signs of mixing. A clear 137Cs peak was found in the UMR core, which was correlated to 1963. The PCB vertical distribution in UMR core was similar to the historical trend in Aroclor production observed in Great Lakes cores, with a peak close to the 137Cs peak, suggesting a date near 1960. In general, PCB congener profiles in both cores resembled the Iowa soil background signal. We concluded that despite evidence of mixing in the Iowa River core, both cores retain the PCB signature of historical and regional environmental exposure. Further, our results indicate that this iconic waterway has a long history of PCBs that reflects national production and use. PMID:26547030

Bisphenol A Impairs Follicle Growth, Inhibits Steroidogenesis, and Downregulates Rate-Limiting Enzymes in the Estradiol Biosynthesis Pathway

PubMed Central

Peretz, Jackye; Gupta, Rupesh K.; Singh, Jeffrey; Hernández-Ochoa, Isabel; Flaws, Jodi A.

2011-01-01

Bisphenol A (BPA) is used as the backbone for plastics and epoxy resins, including various food and beverage containers. BPA has also been detected in 95% of random urine samples and ovarian follicular fluid of adult women. Few studies have investigated the effects of BPA on antral follicles, the main producers of sex steroid hormones and the only follicles capable of ovulation. Thus, this study tested the hypothesis that postnatal BPA exposure inhibits antral follicle growth and steroidogenesis. To test this hypothesis, antral follicles isolated from 32-day-old FVB mice were cultured with vehicle control (dimethyl sulfoxide [DMSO]), BPA (4.4–440μM), pregnenolone (10 μg/ml), pregnenolone + BPA 44μM, and pregnenolone + BPA 440μM. During the culture, follicles were measured for growth daily. After the culture, media was subjected to ELISA for hormones in the estradiol biosynthesis pathway, and follicles were processed for quantitative real-time PCR of steroidogenic enzymes. The results indicate that BPA (440μM) inhibits follicle growth and that pregnenolone cotreatment was unable to restore/maintain growth. Furthermore, BPA 44 and 440μM inhibit progesterone, dehydroepiandrosterone, androstenedione, estrone, testosterone, and estradiol production. Pregnenolone cotreatment was able to increase production of pregnenolone, progesterone, and dehydroepiandrosterone and maintain androstenedione and estrone levels in BPA-treated follicles compared with DMSO controls but was unable to protect testosterone or estradiol levels. Furthermore, pregnenolone was unable to protect follicles from BPA-(44–440 μM) induced inhibition of steroidogenic enzymes compared with the DMSO control. Collectively, these data show that BPA targets the estradiol biosynthesis pathway in the ovary. PMID:20956811

The estradiol 17-β concentration in mice after treated with ethanolic leaf extract of Azadirachta indica (neem)

NASA Astrophysics Data System (ADS)

Sitasiwi, Agung Janika; Isdadiyanto, Sri; Mardiati, Siti Muflichatun

2017-05-01

This research was conducted to determine the effect of ethanolic leaf extract of Azadirachta indica (Neem) on plasma estradiol 17-β synthesis in mice. Thirty virgin female mice (Swiss Webster strain) between 2.5 and 3 months old (25 ± 2.5 g body weight) were used as the experimental sample. The mice were divided into five groups: K-group were administered tap water; K+ group were administered contraceptive pills; P1 to P3 group were administered orally with ethanolic A. indica leaf extract at doses of 8.4, 11.2, and 14 mg/animal/day, respectively. The regularity of the estrous cycle was monitored during treatment. The mice were sacrificed after being treated orally for 21 days and blood was collected by cardiac puncture under chloroform anesthesia. The estradiol concentration was measured by ELISA. Ovaries were processed with the paraffin method and HE staining. Our results showed that the estrous cycle irregularity of treated groups was higher than K-group. The estradiol concentration was significantly different (p<0.05) compared to the control group (25.02 ± 1.16 pg/mL in the control group and 18.86 ± 2.21 pg/mL in treated group but there was no significant difference (p>0.05) between the treated groups. The atresia follicle number was significantly different (p<0.05), not compared to the control group but between treated groups also. It can be concluded that Neem extracts disrupt the estradiol 17-β concentration by interference with follicle development in the ovaries so that the regularity of estrous cycle was disrupted.

Estradiol prevents ozone-induced increases in brain lipid peroxidation and impaired social recognition memory in female rats.

PubMed

Guevara-Guzmán, R; Arriaga, V; Kendrick, K M; Bernal, C; Vega, X; Mercado-Gómez, O F; Rivas-Arancibia, S

2009-03-31

There is increasing concern about the neurodegenerative and behavioral consequences of ozone pollution in industrialized urban centers throughout the world and that women may be more susceptible to brain neurodegenerative disorders. In the present study we have investigated the effects of chronic (30 or 60 days) exposure to ozone on olfactory perception and memory and on levels of lipid peroxidation, alpha and beta estrogen receptors and dopamine beta-hydroxylase in the olfactory bulb in ovariectomized female rats. The ability of 17beta-estradiol to prevent these effects was then assessed. Results showed that ozone exposure for 30 or 60 days impaired formation/retention of a selective olfactory recognition memory 120 min after exposure to a juvenile stimulus animal with the effect at 60 days being significantly greater than at 30 days. They also showed impaired speed in locating a buried chocolate reward after 60 days of ozone exposure indicating some loss of olfactory perception. These functional impairments could all be prevented by coincident estradiol treatment. In the olfactory bulb, levels of lipid peroxidation were increased at both 30- and 60-day time-points and numbers of cells with immunohistochemical staining for alpha and beta estrogen receptors, and dopamine beta-hydroxylase were reduced as were alpha and beta estrogen receptor protein levels. These effects were prevented by estradiol treatment. Oxidative stress damage caused by chronic exposure to ozone does therefore impair olfactory perception and social recognition memory and may do so by reducing noradrenergic and estrogen receptor activity in the olfactory bulb. That these effects can be prevented by estradiol treatment suggests increased susceptibility to neurodegenerative disorders in aging women may be contributed to by reduced estrogen levels post-menopause.

Mastitis outcomes on pre-ovulatory follicle diameter, estradiol concentrations, subsequent luteal profiles and conception rate in Buffaloes.

PubMed

Mansour, Mohamed Mohsen; Zeitoun, Moustafa M; Hussein, Fekry M

2017-06-01

The objectives of this study was to investigate the outcome of mastitis, in its clinical or subclinical forms, on the mean diameter of pre-ovulatory follicle (POF), plasma estradiol concentration on the day of estrus, subsequent luteal profile and subsequent conception rate in buffaloes. Sixty dairy buffalo (Bubalus bubalus) conducted in this study were divided into three groups {healthy (H), n=20; subclinical mastitis (SCM), n=18; and clinical mastitis (CM), n=22}. Ultrasonography of ovaries revealed that mean diameter of POF was larger (P<0.05) in H buffalo (14.35mm) compared to SCM (12.40mm) and CM (10.25mm). Also, plasma estradiol concentration on the day of estrus was higher (P<0.05) in H buffalo compared to SCM and CM counterparts; 34.95 vs. 32.87 and 27.50pg/ml, respectively. Besides, positive correlation was observed between the POF diameter with plasma estradiol concentration in H, SCM and CM buffaloes (r=0.64, 0.74, 0.72 respectively, P<0.05). Moreover, positive correlations (P<0.01) were found on days 9, 12, 16, and 21 post-ovulation between POF diameter and luteal profile. Thus, the conception rate in H buffalo was higher (P<0.05) compared with SCM and CM counterparts; 55% vs. 38.89 and 18.18%, respectively. In conclusion, mastitis in its clinical or subclinical forms disrupts the functioning of the pre-ovulatory follicle on the day of estrus, associated with low follicular estradiol production, resulting in suppression to subsequent luteal profile leading to substantial decrease in pregnancy consequence of buffaloes. Copyright © 2017 Elsevier B.V. All rights reserved.

Pentagastrin-induced hemoconcentration in healthy volunteers and patients with panic disorder: effect of pretreatment with ethinyl estradiol.

PubMed

Le Melledo, Jean Michel; Perez-Parada, Jorge; Morrow, Jarret; Bellavance, Francois; Lara, Nathalie; Jahandar, Farideh; Granger, Robert; Tait, Glendon; McManus, Karen

2011-01-01

Panic disorder has been associated with both an increased risk of coronary events as well as an increased risk of stroke. Hemoconcentration, with both a decrease in plasma volume and an increase in plasma viscosity, is a possible contributor to the risk of acute ischemic events. Our objectives were to demonstrate the process of hemoconcentration in response to induced panic symptoms and to assess the effect of pretreatment with ethinyl estradiol on panic-induced hemoconcentration. Fifteen male patients with panic disorder and 10 male healthy volunteers were included in a double-blind cross-over placebo-controlled design consisting of two injections of pentagastrin following randomized pretreatment with placebo and ethinyl estradiol. Plasma levels of hematocrit and hemoglobin were assessed at baseline and post-injections, and used to calculate an indirect estimation of the change in plasma volume. Pentagastrin-induced panic symptoms were associated with a mean decrease in plasma volume of 4.8% in the placebo pretreatment condition. Pretreatment with ethinyl estradiol attenuated this effect. The acute hemoconcentration observed in relation to pentagastrin-induced panic symptoms may be relevant to the increased risk of stroke and acute coronary events found in patients with panic disorder.

Effect of Saraca asoca (Asoka) on estradiol-induced keratinizing metaplasia in rat uterus.

PubMed

Shahid, Adangam Purath; Salini, Sasidharan; Sasidharan, Nanu; Padikkala, Jose; Raghavamenon, Achuthan Chathrattil; Babu, Thekkekara Devassy

2015-09-01

Estrogen-mediated uterus endometrium instability is considered as one of the etiological factors in dysfunctional uterine bleeding (DUB) and uterine cancer. Saraca asoca (Family: Fabaceae) and its fermented preparation, Asokarishta, are extensively used as uterine tonic to treat gynecological disorders in Ayurveda. The present study evaluated the effect of S. asoca (Asoka) on estrogen-induced endometrial thickening of rat uterus. Endometrial thickening was induced by intraperitoneal injection of estradiol (20 μg/kg b.wt) to 8-day-old immature rats for alternate 5 days. Methanolic extract (200 mg/kg b. wt) from S. asoca bark was given orally along with estradiol. Uterus endometrial thickening was analyzed histopathologically and serum estrogen level by radioimmunoassay (RIA). Cyclooxygenase (COX-2) expression in rat uterus was also estimated by Western blot. Anti-inflammatory activity of the extract was analyzed by formalin- and carrageenan-elicited paw edema models in mouse. Uterus endometrium proliferation and keratinized metaplasia with seven to eight stratified epithelial layers on day 16 was observed in rats administered with estradiol. Treatment with S. asoca reduced the thickening to two to four layers and the serum estrogen level diminished significantly to 82.9±12.87 pg/mL compared to rats administered with estrogen alone (111.2±10.68 pg/mL). A reduction of formalin- and carrageenan-induced paw edema in mouse by S. asoca extract was observed. Lower level of lipopolysaccharides (LPS)-induced COX-2 enzyme in rat uterus by the extract further confirms its anti-inflammatory activity. Present study reveals the antiproliferative and antikeratinizing effects of S. asoca in uterus endometrium possibly through its anti-estrogenic and anti-inflammatory properties.

Subcellular localization of estradiol receptor in MCF7 cells studied with nanogold-labelled antibody fragments.

PubMed

Kessels, M M; Qualmann, B; Thole, H H; Sierralta, W D

1998-01-01

Ultrastructural localization studies of estradiol receptor in hormone-deprived and hormone-stimulated MCF7 cells were done using F(ab') fragments of three different antibodies (#402, 13H2, HT277) covalently linked to nanogold. These ultra-small, non-charged immunoreagents, combined with a size-enlargement by silver enhancement, localized estradiol receptor in both nuclear and cytoplasmic areas of non-stimulated target cells; stimulation with the steroid induced a predominantly nuclear labelling. In the cytoplasm of resting cells, tagging was often observed at or in the proximity of stress fibers. In the nucleus a large proportion of receptor was found inside the nucleolus, specially with the reagent derived from antibody 13H2. We postulate that different accessibilities of receptor epitopes account for the different labelling densities observed at cytoskeletal elements and the nucleoli.

Estradiol agonists inhibit human LoVo colorectal-cancer cell proliferation and migration through p53.

PubMed

Hsu, Hsi-Hsien; Kuo, Wei-Wen; Ju, Da-Tong; Yeh, Yu-Lan; Tu, Chuan-Chou; Tsai, Ying-Lan; Shen, Chia-Yao; Chang, Sheng-Huang; Chung, Li-Chin; Huang, Chih-Yang

2014-11-28

To investigate the effects of 17β-estradiol via estrogen receptors (ER) or direct administration of ER agonists on human colorectal cancer. LoVo cells were established from the Bioresource Collection and Research Center and cultured in phenol red-free DMEM (Sigma, United States). To investigate the effects of E2 and/or ER selective agonists on cellular proliferation, LoVo colorectal cells were treated with E2 or ER-selective agonists for 24 h and 48 h and subjected to the MTT (Sigma) assay to find the concentration. And investigate the effects of E2 and/or ER selective agonists on cell used western immunoblotting to find out the diversification of signaling pathways. In order to observe motility and migration the wound healing assay and a transwell chamber (Neuro Probe) plate were tased. For a quantitative measure, we counted the number of migrating cells to the wound area post-wounding for 24 h. We further examined the cellular migration-regulating factors urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and matrix metalloproteinase (MMP)-9 in human LoVo cells so gelatin zymography that we used and gelatinolytic activity was visualized by Coomassie blue staining. And these results are presented as means ± SE, and statistical comparisons were made using Student's t-test. The structure was first compared with E2 and ER agonists. We then treated the LoVo cells with E2 and ER agonists (10(-8) mol/L) for 24 h and 48 h and subsequently measured the cell viability using MTT assay. Our results showed that treatment with 17β-estradiol and/or ER agonists in human LoVo colorectal cancer cells activated p53 and then up-regulated p21 and p27 protein levels, subsequently inhibiting the downstream target gene, cyclin D1, which regulates cell proliferation. Taken together, our findings demonstrate the anti-tumorigenesis effects of 17β-estradiol and/or ER agonists and suggest that these compounds may prove to be a potential alternative

A hormone pulse induces transient changes in the subcellular distribution and leads to a lysosomal accumulation of the estradiol receptor alpha in target tissues.

PubMed

Qualmann, B; Kessels, M M; Thole, H H; Sierralta, W D

2000-06-01

An intrauterine pulse-stimulation with estradiol induced changes in the subcellular localization of estrogen receptor alpha in porcine endometrium, as detected with F(ab') fragments of various anti-receptor antibodies covalently linked to nanogold. The low-sterically hindered immunoreagents--recognizing different epitopes within the hormone binding domain--allowed for an efficient immunolabeling of estradiol receptor alpha, detecting it both in the cytoplasm and the nucleus of nonstimulated epithelium cells. In the cytoplasm, the receptor often seemed to be associated with actin filaments and the endoplasmatic reticulum. After the stimulation with estradiol, a predominantly nuclear localization and a labeling of nucleoli was observed. Our immunoelectron microscopy study demonstrates a localization of the receptor in cytoplasmic organelles that increased after the hormone pulse. These organelles exhibited the morphological properties of lysosomes and relocated to the perinuclear area. In analogous cytoplasmic organelles, the presence of cathepsin D was detected via indirect immunogold labeling, justifying their classification as lysosomes. Quantitative examinations revealed that not only the number of lysosomes in the proximity of the nucleus but also their immunostaining for estradiol receptor alpha increased significantly after the hormone pulse. Thus, estradiol induces both the rapid shift of receptor into the nucleus, a slower perinuclear accumulation of lysosomes and an increase of lysosomal ERalpha-immunoreactivity. These results suggest a role for lysosomes in the degradation of receptor shuttling out of the nucleus. This could serve as termination of the estradiol receptor alpha-dependent activation of target cells. This hypothesis is strengthened by the fact that the receptor content in uterine tissue declined drastically few hours after the hormone pulse.

Estradiol, progesterone and genistein differentially regulate levels of aquaporin (AQP)-1, 2, 5 and 7 expression in the uteri of ovariectomized, sex-steroid deficient rats.

PubMed

Chinigarzadeh, Asma; Muniandy, Sekaran; Salleh, Naguib

2016-11-01

In this study, effects of estradiol, progesterone and genistein on uterine aquaporin (AQP)-1, 2, 5 and 7 expression were investigated in sex-steroid deficient state which could help to elucidate the mechanisms underlying uterine fluid volume changes that were reported under these hormone and hormone-like compound influences. Uteri from ovariectomized, female Sprague-Dawley rats receiving seven days estradiol, progesterone or genistein (25, 50 and 100mg/kg/day) were harvested and levels of AQP-1, 2, 5 and 7 proteins and mRNAs were determined by Western blotting and Real-time PCR (qPCR) respectively. Distribution of these proteins in uterus was observed by immunohistochemistry. Genistein caused a dose-dependent increase in uterine AQP-1, 2, 5 and 7 protein and mRNA expression, however at the levels lower than following estradiol or progesterone stimulations. Effects of genistein were antagonized by estradiol receptor blocker, ICI 182780. Estradiol caused the highest AQP-2 protein and mRNA expression while progesterone caused the highest AQP-1, 5 and 7 protein and mRNA expression in uterus. AQP-1, 2, 5 and 7 protein were found to be distributed in the myometrium as well as in uterine luminal and glandular epithelia and endometrial blood vessels. In conclusion, the observed effects of estradiol, progesterone and genistein on uterine AQP-1, 2, 5 and 7 expression could help to explain the differences in the amount of fluid accumulated in the uterus under these different conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Transport of estradiol-17β-glucuronide, estrone-3-sulfate and taurocholate across the endoplasmic reticulum membrane: evidence for different transport systems.

PubMed

Wlcek, Katrin; Hofstetter, Lia; Stieger, Bruno

2014-03-01

Important reactions of drug metabolism, including UGT mediated glucuronidation and steroidsulfatase mediated hydrolysis of sulfates, take place in the endoplasmic reticulum (ER) of hepatocytes. Consequently, UGT generated glucuronides, like estradiol-17β-glucuronide, have to be translocated back into the cytoplasm to reach their site of excretion. Also steroidsulfatase substrates, including estrone-3-sulfate, have to cross the ER membrane to reach their site of hydrolysis. Based on their physicochemical properties such compounds are not favored for passive diffusion and therefore likely necessitate transport system(s) to cross the ER membrane in either direction. The current study aims to investigate the transport of taurocholate, estradiol-17β-glucuronide, and estrone-3-sulfate in smooth (SER) and rough (RER) endoplasmic reticulum membrane vesicles isolated from Wistar and TR(-) rat liver. Time-dependent and bidirectional transport was demonstrated for taurocholate, showing higher uptake rates in SER than RER vesicles. For estradiol-17β-glucuronide a fast time-dependent efflux with similar efficiencies from SER and RER but no clear protein-mediated uptake was shown, indicating an asymmetric transport system for this substrate. Estrone-3-sulfate uptake was time-dependent and higher in SER than in RER vesicles. Inhibition of steroidsulfatase mediated estrone-3-sulfate hydrolysis decreased estrone-3-sulfate uptake but had no effect on taurocholate or estradiol-17β-glucuronide transport. Based on inhibition studies and transport characteristics, three different transport mechanisms are suggested to be involved in the transport of taurocholate, estrone-3-sulfate and estradiol-17β-glucuronide across the ER membrane. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Increase in endogenous estradiol in the progeny of obese rats is associated with precocious puberty and altered follicular development in adulthood.

PubMed

Ambrosetti, Valery; Guerra, Marcelo; Ramírez, Luisa A; Reyes, Aldo; Álvarez, Daniela; Olguín, Sofía; González-Mañan, Daniel; Fernandois, Daniela; Sotomayor-Zárate, Ramón; Cruz, Gonzalo

2016-07-01

Maternal obesity during pregnancy has been related with several pathological states in offspring. However, the impact of maternal obesity on reproductive system on the progeny is beginning to be elucidated. In this work, we characterize the effect of maternal obesity on puberty onset and follicular development in adult offspring in rats. We also propose that alterations in ovarian physiology observed in offspring of obese mothers are due to increased levels of estradiol during early development. Offspring of control dams and offspring of dams exposed to a high-fat diet (HF) were studied at postnatal days (PND) 1, 7, 14, 30, 60, and 120. Body weight and onset of puberty were measured. Counting of ovarian follicles was performed at PND 60 and 120. Serum estradiol, estriol, androstenedione, FSH, LH, and insulin levels were measured by ELISA. Hepatic CYP3A2 expression was determined by Western blot. HF rats had a higher weight than controls at all ages and they also had a precocious puberty. Estradiol levels were increased while CYP3A2 expression was reduced from PND 1 until PND 60 in HF rats compared to controls. Estriol was decreased at PND60 in HF rats. Ovaries from HF rats had a decrease in antral follicles at PND60 and PND120 and an increase in follicular cysts at PND60 and PND120. In this work, we demonstrated that maternal obesity in rats alters follicular development and induces follicular cysts generation in the adult offspring. We observed that maternal obesity produces an endocrine disruption through increasing endogenous estradiol in early life. A programmed failure in hepatic metabolism of estradiol is probably the cause of its increase.

17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib.

PubMed

Girgert, Rainer; Emons, Günter; Gründker, Carsten

2017-02-01

Triple-negative breast cancers (TNBCs) are neither susceptible to endocrine therapy due to a lack of estrogen receptor α expression nor trastuzumab. TNBCs frequently overexpress epidermal growth factor receptor (EGFR) and membrane bound estrogen receptor, GPER. To a certain extent the growth of TNBCs is stimulated by 17β-estradiol via GPER. We analyzed whether inhibition of EGFR by gefitinib reduces the expression of GPER and subsequent signal transduction in TNBC cells. Dependence of proliferation on 17β-estradiol was determined using Alamar Blue assay. Expression of GPR30 and activation of c-src, EGFR and cAMP-responsive element binding (CREB) protein by 17β-estradiol was analyzed by western blotting. Expression of c-fos, cyclin D1 and aromatase was determined using RT-PCR. Gefitinib reduced GPER expression concentration‑ and time‑dependently. In HCC70 cells, GPER expression was reduced to 15±11% (p<0.05) after treatment with 200 nM gefitinib for four days, and in HCC1806 cells GPER expression was reduced to 39±5% (p<0.01) of the control. 17β-estradiol significantly increased the percentage of HCC1806 cells within 7 days to 145±29% of the control (HCC70, 110±8%). This increase in cell growth was completely prevented in both TNBC cell lines after GPR30 expression was downregulated by treatment with 200 nM gefitinib. In HCC1806 cells, activation of c-src was increased by 17β-estradiol to 350±50% (p<0.01), and gefitinib reduced src activation to 110%. Similar results were obtained in the HCC70 cells. Phosphorylation of EGFR increased to 240±40% (p<0.05) in the HCC1806 cells treated with 17β-estradiol (HCC70, 147±25%). Gefitinib completely prevented this activation. Phosphorylation of CREB and induction of c-fos, cyclin D1 and aromatase expression by 17β-estradiol were all prevented by gefitinib. These experiments conclusively show that reduction of GPER expression is a promising therapeutic approach for TNBC.

Fate of 4-nonylphenol and 17β-estradiol in the Redwood River of Minnesota

USGS Publications Warehouse

Writer, Jeffrey H.; Ryan, Joseph N.; Keefe, Steffanie H.; Barber, Larry B.

2012-01-01

The majority of previous research investigating the fate of endocrine-disrupting compounds has focused on single processes generally in controlled laboratory experiments, and limited studies have directly evaluated their fate and transport in rivers. This study evaluated the fate and transport of 4-nonylphenol, 17β-estradiol, and estrone in a 10-km reach of the Redwood River in southwestern Minnesota. The same parcel of water was sampled as it moved downstream, integrating chemical transformation and hydrologic processes. The conservative tracer bromide was used to track the parcel of water being sampled, and the change in mass of the target compounds relative to bromide was determined at two locations downstream from a wastewater treatment plant effluent outfall. In-stream attenuation coefficients (kstream) were calculated by assuming first-order kinetics (negative values correspond to attenuation, whereas positive values indicate production). Attenuation of 17β-estradiol (kstream = −3.2 ± 1.0 day–1) was attributed primarily due to sorption and biodegradation by the stream biofilm and bed sediments. Estrone (kstream = 0.6 ± 0.8 day–1) and 4-nonylphenol (kstream = 1.4 ± 1.9 day–1) were produced in the evaluated 10-km reach, likely due to biochemical transformation from parent compounds (17β-estradiol, 4-nonylphenolpolyethoxylates, and 4-nonyphenolpolyethoxycarboxylates). Despite attenuation, these compounds were transported kilometers downstream, and thus additive concentrations from multiple sources and transformation of parent compounds into degradates having estrogenic activity can explain their environmental persistence and widespread observations of biological disruption in surface waters.

Physiological and brain alterations produced by high-fat diet in male and female rats can be modulated by increased levels of estradiol during critical periods of development.

PubMed

Carrillo, Beatriz; Collado, Paloma; Díaz, Francisca; Chowen, Julie A; Pérez-Izquierdo, Mª Ángeles; Pinos, Helena

2017-07-11

Overnutrition due to a high-fat diet (HFD) can increase the vulnerability of the metabolic system to maladjustments. Estradiol has an inhibitory role on food intake and this hormone has demonstrated to be a crucial organizer during brain development. Our aim was to determine whether increased levels of estradiol in the early postnatal period modulate the alterations in metabolism and brain metabolic circuits produced by overnutrition. Twenty-four male and 24 female Wistar rats were submitted to a HFD (34.9% fat) or a control diet (5% fat) from gestational day 6. From postnatal (P) 6 to P13, both control and HFD groups were administered a s.c. injection of vehicle or estradiol benzoate (0.4 mg/kg), resulting in eight experimental groups (n = 6 in each group). Body weight, food intake and subcutaneous, visceral, and brown fat pads were measured. Agouti-related peptide, neuropeptide Y, orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay and plasma estradiol levels were measured by ELISA. Males fed a HFD showed an increase in body weight and the amount of visceral and subcutaneous fat, which was coincident with an increase in the number of kilocalories ingested. Neonatal estradiol treatment restored the body weight and subcutaneous fat of HFD males to control levels. Hypothalamic POMC mRNA levels in HFD females were increased with respect to control females. This increase was reverted with estradiol treatment during development. HFD and estradiol treatment have different effects on males and females. Overnutrition affects physiological parameters, such as body weight, visceral, and subcutaneous fat content, in males, while females present alterations in hypothalamic POMC mRNA levels. Hence, the increase in estradiol levels during a period that is critical for the programing of the feeding system can modulate some of the alterations produced by the continuous intake of high-fat content food.

Regulation of GnRH I receptor gene expression by the GnRH agonist triptorelin, estradiol, and progesterone in the gonadotroph-derived cell line alphaT3-1.

PubMed

Weiss, J M; Polack, S; Treeck, O; Diedrich, K; Ortmann, O

2006-08-01

The secretion of luteinizing hormone (LH) and the GnRH receptor (GnRH-R) concentration are modulated by ovarian steroids and GnRH. To elucidate whether this regulation is due to alterations at the transcriptional level, we examined the GnRH I-R mRNA expression in the gonadotroph-derived cell line alphaT3-1 treated with different estradiol and progesterone paradigms and the GnRH I agonist triptorelin. alphaT3-1 cells were treated with different steroid paradigms: 1 nM estradiol or 100 nM progesterone for 48 h alone or in combination. Cells were exposed to 10 nM or 100 pM triptorelin for 30 min, 3 h, 9 h, or, in pulsatile way, with a 5-min pulse per hour. The GnRH I-R mRNA was determined by Northern blot analysis. GnRH I-R mRNA from cells treated with continuous triptorelin decreased in a time- and concentration-dependent manner. Pulsatile triptorelin increased GnRH I-R gene expression. Progesterone alone further enhanced this effect, whereas estradiol and its combination with progesterone diminished it. Continuous combined treatment with estradiol and progesterone lead to a significant decrease of GnRH I-R mRNA by 30% and by 35% for estradiol alone. The addition of 10 nM triptorelin for 30 min or 3 h could not influence that steroid effect. In conclusion, estradiol and progesterone exclusively decreased GnRH I-R mRNA in alphaT3-1 cells no matter whether they are treated additionally with the GnRH I agonist triptorelin. The enhanced sensitivity of gonadotrophs and GnRH I-R upregulation by estradiol is not due to increased GnRH I gene expression because GnRH I-R mRNA is downregulated by estradiol and progesterone. Other pathways of the GnRH I-R signal transduction might be involved.

Protective Actions of 17β-Estradiol and Progesterone on Oxidative Neuronal Injury Induced by Organometallic Compounds

PubMed Central

Ishihara, Yasuhiro; Takemoto, Takuya; Yamazaki, Takeshi

2015-01-01

Steroid hormones synthesized in and secreted from peripheral endocrine glands pass through the blood-brain barrier and play a role in the central nervous system. In addition, the brain possesses an inherent endocrine system and synthesizes steroid hormones known as neurosteroids. Increasing evidence shows that neuroactive steroids protect the central nervous system from various harmful stimuli. Reports show that the neuroprotective actions of steroid hormones attenuate oxidative stress. In this review, we summarize the antioxidative effects of neuroactive steroids, especially 17β-estradiol and progesterone, on neuronal injury in the central nervous system under various pathological conditions, and then describe our recent findings concerning the neuroprotective actions of 17β-estradiol and progesterone on oxidative neuronal injury induced by organometallic compounds, tributyltin, and methylmercury. PMID:25815107

Pharmacokinetic drug-drug interaction assessment of LCZ696 (an angiotensin receptor neprilysin inhibitor) with omeprazole, metformin or levonorgestrel-ethinyl estradiol in healthy subjects.

PubMed

Gan, Lu; Jiang, Xuemin; Mendonza, Anisha; Swan, Therese; Reynolds, Christine; Nguyen, Joanne; Pal, Parasar; Neelakantham, Srikanth; Dahlke, Marion; Langenickel, Thomas; Rajman, Iris; Akahori, Mizuki; Zhou, Wei; Rebello, Sam; Sunkara, Gangadhar

2016-01-01

LCZ696 is a novel angiotensin receptor neprilysin inhibitor in development for the treatment of cardiovascular diseases. Here, we assessed the potential for pharmacokinetic drug-drug interaction of LCZ696 (400 mg, single dose or once daily [q.d.]) when co-administered with omeprazole 40 mg q.d. (n = 28) or metformin 1000 mg q.d. (n = 27) or levonorgestrel-ethinyl estradiol 150/30 μg single dose (n = 24) in three separate open-label, single-sequence studies in healthy subjects. Pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan), metformin, and levonorgestrel-ethinyl estradiol were assessed. Omeprazole did not alter the AUCinf of sacubitril and pharmacokinetics of LBQ657; however, 7% decrease in the Cmax of sacubitril, and 11% and 13% decreases in AUCinf and Cmax of valsartan were observed. Co-administration of LCZ696 with metformin had no significant effect on the pharmacokinetics of LBQ657 and valsartan; however, AUCtau,ss and Cmax,ss of metformin were decreased by 23%. Co-administration of LCZ696 with levonorgestrel-ethinyl estradiol had no effect on the pharmacokinetics of ethinyl estradiol and LBQ657 or AUCinf of levonorgestrel. The Cmax of levonorgestrel decreased by 15%, and AUCtau,ss and Cmax,ss of valsartan decreased by 14% and 16%, respectively. Co-administration of LCZ696 with omeprazole, metformin, or levonorgestrel-ethinyl estradiol was not associated with any clinically relevant pharmacokinetic drug interactions. © 2015, The American College of Clinical Pharmacology.

A comparative evaluation of treatments with 17β-estradiol and its brain-selective prodrug in a double-transgenic mouse model of Alzheimer's disease.

PubMed

Tschiffely, Anna E; Schuh, Rosemary A; Prokai-Tatrai, Katalin; Prokai, Laszlo; Ottinger, Mary Ann

2016-07-01

Estrogens are neuroprotective and, thus, potentially useful for the therapy of Alzheimer's disease; however, clinical use of hormone therapy remains controversial due to adverse peripheral effects. The goal of this study was to investigate the benefits of treatment with 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), a brain-selective prodrug of 17β-estradiol, in comparison with the parent hormone using APPswe/PS1dE9 double transgenic mice to model the pathology of the disease. Ovariectomized and intact females were continuously treated with vehicle, 17β-estradiol, or DHED via subcutaneous osmotic pumps from 6 to 8months of age. We confirmed that this prolonged treatment with DHED did not stimulate uterine tissue, whereas 17β-estradiol treatment increased uterine weight. Amyloid precursor protein decreased in both treatment groups of intact, but not in ovariectomized double transgenic females in which ovariectomy already decreased the expression of this protein significantly. However, reduced brain amyloid-β peptide levels could be observed for both treatments. Consequently, double-transgenic ovariectomized and intact mice had higher cognitive performance compared to untreated control animals in response to both estradiol and DHED administrations. Overall, the tested brain-selective 17β-estradiol prodrug proved to be an effective early-stage intervention in an Alzheimer's disease-relevant mouse model without showing systemic impact and, thus, warrants further evaluation as a potential therapeutic candidate. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel.

PubMed

Olsson, B; Landgren, B M

2001-11-01

Tolterodine is an antimuscarinic agent for the treatment of overactive bladder, a chronic condition that is particularly common in women. Given the prevalence pattern of overactive bladder and the widespread use of oral contraception, circumstances are likely to arise in which physicians may wish to prescribe tolterodine for patients already taking oral contraceptives. Based on a search of MEDLINE from 1990 to 2001, there have been no studies of whether concomitant use of these agents entails a risk of drug-drug interaction or conception. This study investigated the effects of tolterodine on the pharmacokinetics and pharmacodynamics of a low-dose combination oral contraceptive (ethinyl estradiol 30 microg/levonorgestrel 150 microg). This was an open-label, randomized, 2-period crossover study in healthy women. Oral contraception was given for 21 days either alone or in combination with oral tolterodine 2 mg BID (on days 1-14) over two 28-day contraceptive cycles. Pharmacokinetic assessments were performed on day 14 based on plasma levels of ethinyl estradiol and levonorgestrel up to 24 hours after dosing and serum tolterodine levels at 1 to 3 hours after dosing. The potential for pharmacodynamic interaction was assessed in terms of the risk of failure of suppression of ovulation based on serum levels of estradiol and progesterone measured throughout each cycle. Twenty-four healthy women (age, 23-41 years [mean, 30 years]; height, 155-178 cm [mean, 167 cm]; body weight, 51-75 kg [mean, 64 kg]) participated in the study. There was no evidence of a pharmacokinetic interaction between tolterodine and the steroid hormones in the oral contraceptive used, nor did the oral contraceptive show any relevant pharmacokinetic interaction with tolterodine. Serum levels of estradiol and progesterone indicated suppression of ovulation in both treatment periods. In this selected population. coadministration of tolterodine did not affect the contraceptive efficacy of a low

17ß-Estradiol Is Necessary for Extinction of Cocaine Seeking in Female Rats

ERIC Educational Resources Information Center

Twining, Robert C.; Tuscher, Jennifer J.; Doncheck, Elizabeth M.; Frick, Karyn M.; Mueller, Devin

2013-01-01

Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17ß-estradiol (E[subscript 2]) affects expression and extinction of cocaine seeking in female rats. Using a…

Estradiol regulates the insulin-like growth factor-I (IGF-I) signalling pathway: A crucial role of phosphatidylinositol 3-kinase (PI 3-kinase) in estrogens requirement for growth of MCF-7 human breast carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernard, Laurence; Legay, Christine; Adriaenssens, Eric

2006-12-01

Estrogens can stimulate the proliferation of estrogen-responsive breast cancer cells by increasing their proliferative response to insulin-like growth factors. With a view to investigating the molecular mechanisms implicated, we studied the effect of estradiol on the expression of proteins implicated in the insulin-like growth factor signalling pathway. Estradiol dose- and time-dependently increased the expression of insulin receptor substrate-1 and the p85/p110 subunits of phosphatidylinositol 3-kinase but did not change those of ERK2 and Akt/PKB. ICI 182,780 did not inhibit estradiol-induced IRS-1 and p85 expression. Moreover, two distinct estradiol-BSA conjugate compounds were as effective as estradiol in inducing IRS-1 and p85/p110more » expression indicating the possible implication of an estradiol membrane receptor. Comparative analysis of steroids-depleted and steroids-treated cells showed that IGF-I only stimulates cell growth in the latter condition. Nevertheless, expression of a constitutively active form of PI 3-kinase in steroid-depleted cells triggers proliferation. These results demonstrate that estradiol positively regulates essential proteins of the IGF signalling pathway and put in evidence that phosphatidylinositol 3-kinase plays a central role in the synergistic pro-proliferative action of estradiol and IGF-I.« less

Computerized optimization of radioimmunoassays for hCG and estradiol: an experimental evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yanagishita, M.; Rodbard, D.

1978-07-15

The mathematical and statistical theory of radioimmunoassays (RIAs) has been used to develop a series of computer programs to optimize sensitivity or precision at any desired dose level for either equilibrium or nonequilibrium assays. These computer programs provide for the calculation of the equilibrium constants of association and binding capacities for antisera (parameters of Scatchard plots), the association and dissociation rate constants, and prediction of optimum concentration of labeled ligand and antibody and optimum incubation times for the assay. This paper presents an experimental evaluation of the use of these computer programs applied to RIAs for human chorionic gonadotropin (hCG)more » and estradiol. The experimental results are in reasonable semiquantitative agreement with the predictions of the computer simulations (usually within a factor of two) and thus partially validate the use of computer techniques to optimize RIAs that are reasonably well behaved, as in the case of the hCG and estradiol RIAs. Further, these programs can provide insights into the nature of the RIA system, e.g., the general nature of the sensitivity and precision surfaces. This facilitates empirical optimization of conditions.« less

Low-dose levonorgestrel and ethinyl estradiol patch and pill: a randomized controlled trial.

PubMed

Kaunitz, Andrew M; Portman, David; Westhoff, Carolyn L; Archer, David F; Mishell, Daniel R; Rubin, Arkady; Foegh, Marie

2014-02-01

To compare a new low-dose levonorgestrel and ethinyl estradiol contraceptive patch (Patch) with a combination oral contraceptive (Pill; 100 micrograms levonorgestrel, 20 micrograms ethinyl estradiol) regarding efficacy, safety, compliance, and unscheduled uterine bleeding. Women (17-40 years; body mass index 16-60) were randomized in a 3:1 ratio to one of two groups: Patch only (13 cycles) or Pill (six cycles) followed by Patch (seven cycles). Investigators evaluated adverse events during cycles 2, 4, 6, 9, and 13. Participants recorded drug administration and uterine bleeding on daily diary cards. Compliance was assessed by measuring levonorgestrel and ethinyl estradiol plasma levels. Pearl Index (pregnancies per 100 woman-years) was calculated to evaluate efficacy. Participants (N=1,504) were randomized to Patch (n=1,129) or Pill (n=375). Approximately 30% were obese, more than 40% were racial or ethnic minorities, and more than 55% were new users of hormonal contraceptives. Laboratory-verified noncompliance (undetectable plasma drug levels) was 11% of Patch and 12.6% of Pill users at cycle 6. Pearl Indices (95% confidence intervals) for the intention-to-treat population (cycles 1-6) were 4.45 (2.34-6.57) for Patch and 4.02 (0.50-7.53) for Pill; excluding laboratory-verified noncompliant participants, Pearl Indices were 2.82 (0.98-4.67) for Patch and 3.80 (0.08-7.52) for Pill (differences not statistically significant). Incidence of unscheduled bleeding and incidence and severity of adverse events were similar for both contraceptives (no statistically significant difference). Efficacy and safety of the new contraceptive Patch are comparable to those of a Pill. Laboratory-verified noncompliance and bleeding profile are similar between the two treatments. The Patch was well tolerated. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01181479. I.

Effects of 17β-estradiol and progesterone on the production of adipokines in differentiating 3T3-L1 adipocytes: Role of Rho-kinase.

PubMed

Pektaş, Mehtap; Kurt, Akif Hakan; Ün, İsmail; Tiftik, Rukiye Nalan; Büyükafşar, Kansu

2015-04-01

Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17β-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco's modified Eagle's medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17β-estradiol (10(-8)-10(-7)M), progesterone (10(-6)-10(-5)M), the Rho-kinase inhibitor, Y-27632 (10(-5)M) and their combination for 8days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17β-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17β-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17β-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17β-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modulation of vitellogenin synthesis through estrogen receptor beta-1 in goldfish (Carassius auratus) juveniles exposed to 17-{beta} estradiol and nonylphenol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soverchia, L.; Ruggeri, B.; Palermo, F.

2005-12-15

Many synthetic chemicals, termed xenoestrogens, have been shown to interact as agonists with the estrogen receptor (ER) to elicit biological responses similar to those of natural hormones. To date, the regulation of vitellogenesis in oviparous vertebrates has been widely used for evaluation of estrogenic effects. Therefore, Carassius auratus juveniles were chosen as a fish model for studying the effects of estradiol-17{beta} and different concentrations (10{sup -6} and 10{sup -7} M) of 4-nonylphenol (4-NP) on the expression of liver ER{beta}-1 subtype; plasma vitellogenin and sex steroids (androgens and estradiol-17{beta}) were also evaluated together with the bioaccumulation process, through mass-spectrometry. C. auratusmore » is a species widespread in the aquatic environment and, on the toxicological point of view, can be considered a good 'sentinel' species. Juveniles of goldfish were maintained in tanks with only tap water or water with different concentrations (10{sup -6} and 10{sup -7} M) of 4-nonylphenol (4-NP), or 10{sup -7} M of estradiol-17{beta}. After 3 weeks of treatment, animals were anesthetized within 5 min after capture, and blood was immediately collected into heparinized syringes by cardiac puncture and stored at -70 deg. C; the gonads were fixed, then frozen and stored at -70 deg. C; the whole fish, liver, and muscle tissues were harvested and immediately stored at -70 deg. C for molecular biology experiments and bioaccumulation measurements. The estrogenic effects of 4-NP were evidenced by the presence of plasma vitellogenin in juveniles exposed both to estradiol-17{beta} and the two doses of 4-NP; moreover, exposure to 4-NP also increased aromatization of androgens, as suggested by decreasing androgens and increasing estradiol-17{beta} plasma levels. The changes of these parameters were in agreement with the increasing transcriptional rate of ER{beta}-1 mRNA in the liver, demonstrating that both estradiol-17{beta} and 4-NP modulate the