J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Aug 5;775(2):209-13.
Sensitive determination method of estradiol in plasma using high-performance liquid chromatography with electrochemical detection.
Yamada H, Yoshizawa K, Hayase T.
Kashima Pharmaceutical Development Laboratories, Mitsubishi Pharma Corporation, 14-Sunayama, Hasaki-machi, Kashima-gun, Ibaraki 314-0255, Japan. yamada.hiroyukm.m-pharma.co.jp
The improvement in the sensitive determination method of estradiol using HPLC with electrochemical detection is described. The improvement was due to the optimization of the potential applied to the electrode of the analytical cell and employment of a guard cell. The detection conditions were optimized from the electrochemical properties of estradiol in acidic and alkaline eluents. The employment of the guard cell drastically decreased the background noise without any reduction in the response of estradiol, and contributed to improvement in the sensitivity. The optimized method combined with pretreatment by liquid-liquid extraction was applied to the determination of estradiol in rat plasma. The detection limit of 8 pg for the standard solution and 24 pg for the plasma sample, which was about 6-8-fold more sensitive compared to the previous reports, was attained. Copyright 2002 Elsevier Science BV.
Endocr Pathol. 1998 Autumn;9(3):261-274.
Remodeling of Hyperplastic Pituitaries in Hypothyroid us-Subunit Knockout Mice After Thyroxine and 1713-Estradiol Treatment: Role of Apoptosis.
Kulig E, Camper SA, Kuecker S, Jin L, Lloyd RV.
Hyperplasia of pituitary thyrotrophs is often associated with hypothyroidism. In this study. the effects of thyroxine and 1 7B-estradiol on thyrotroph hyperplasia was analyzed using a hypothyroid mouse model resulting from targeted disruption of the glycoprotein hormone a-subunit (aSU) gene, which leads to lack of functional thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) and underdevelopment of the thyroid and gonads. Thyroxine replacement for 2 mo resulted in a decrease in the relative percent of thyrotrophs and an increase of lactotrophs and somatotrophs numbers to normal values. A twofold increase in the relative percent of gonadotrophs was observed compared to wild-type mouse pituitary. Treatment for 2 mo with 17B-estradiol led to an increase in lactotroph numbers to normal levels, but had no influence on thyrotroph hyperplasia. Rearrangement of the hyperplastic pituitary phenotype after hormonal replacement proceeded without any evidence of pituitary cell necrosis. A slight increase in apoptotic cell death was observed in hormone-treated pituitaries, and this was localized to TSH cells by double-labeling experiments. Chronic thyroxine treatment resulted in increased expression of Bcl-2 protein in hypertrophied pituitary cells, whereas 17f3-estradiol increased expression of Bad protein in prolactin cells. These results suggest that apoptotic cell death is involved in reversal of thyrotroph hyperplasia in the presence of thyroid hormone. Thyroxine and 17-estradiol may influence cell death in this model by regulating expression of the Bcl-2 protein family in a celltype specific manner.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12114718&dopt=Abstract estradiol [PubMed - as supplied by publisher]
Am J Obstet Gynecol. 2002 Jul;187(1):72-9.
Regulation of matrix metalloproteinase expression by estrogen in fibroblasts that are derived from the pelvic floor.
Moalli PA, Klingensmith WL, Meyn LA, Zyczynski HM.
Department of Obstetrics and Gynecology and Division of Gynecologic Specialties, Magee-Womens Hospital and Magee-Womens Research Institute, University of Pittsburgh, PA 15213, USA.
OBJECTIVE: The purpose of this study was to determine whether estrogen suppresses matrix metalloproteinase-2 and -9 proenzyme expression by fibroblasts that are derived from the supportive connective tissue of the pelvic floor. STUDY DESIGN: A primary fibroblast culture that was developed from a biopsy specimen of the arcus tendineus was treated with interleukin-1 beta (10-15 ng/mL), transforming growth factor-beta 1 (5-15 ng/mL), 17 beta-estradiol (10(-9)-10(-7) mol/L), and Imperial Chemical Industries (ICI) 182 780 (10(-8)-10(-6) mol/L). Cellular and extracellular protein were analyzed by Western blotting and substrate zymography, respectively, for the effect of each treatment on the amount of pro-matrix metalloproteinase-2 and -9 and the membrane type 1 matrix metalloproteinase protein. RESULTS: Both cellular and extracellular pro-matrix metalloproteinase-2 protein were increased by transforming growth factor-beta1 (P =.01) and decreased by estradiol (P <.001) and ICI 182 780 (P =.02 and.002, respectively). Membrane type 1 matrix metalloproteinase was not affected by estradiol, ICI 182 780, interleukin-1 beta, or transforming growth factor-beta 1. Extracellular pro-matrix metalloproteinase-9 was increased by the cytokines interleukin-1 beta (P <.001) and transforming growth factor-beta1 (P <.001) and decreased by estradiol (P <.001) and ICI 182 780 (P <.001). CONCLUSION: The proenzymes of the tissue-degrading matrix metalloproteinases -2 and -9 are decreased by 17-beta estradiol and ICI 182 780.
J Neurobiol. 2003 May;55(2):247-60.
Estradiol initially enhances but subsequently suppresses (via adrenal steroids) granule cell proliferation in the dentate gyrus of adult female rats.
Ormerod BK, Lee TT, Galea LA.
Department of Psychology, The University of British Columbia, Vancouver, Canada V6T 1Z4.
In the dentate gyrus of adult female meadow voles, a high dose of estradiol benzoate (EB) increases (within 4 h) then decreases (within 48) the number of dividing progenitor cells (Ormerod BK, Galea LAM. 2001. Reproductive status regulates cell proliferation within the dentate gyrus of the adult female meadow vole: A possible regulatory role for estradiol. Neurosci 2:169-179). We investigated whether time-dependent EB exposure differentially influences the number of new granule cells produced in the adult female rat dentate gyrus and whether EB-stimulated adrenal activity mediates the decrease in cell proliferation. Ovariectomized rats received either an EB (10 microg in 0.1 mL) or vehicle (0.1 mL) injection either 4 or 48 h (Experiment 1) before a BrdU injection (200 mg/kg) and were perfused 24 h later to assess the number of new cells. Relative to vehicle, the number of new cells increased following a 4 h exposure (p < or = 0.04) but decreased following a 48 h exposure (p < or = 0.006) to EB. In Experiment 2, the number of new cells within the dentate gyrus of ovariectomized and adrenalectomized females did not significantly differ between groups exposed to EB versus vehicle for 48 h prior to BrdU administration, suggesting the decreased number of new cells observed within the dentate gyrus of adrenal-intact adult female rats is mediated by EB-stimulated adrenal activity. We conclude that estradiol dynamically regulates cell proliferation within the dentate gyrus of adult female rats in the time-dependent manner observed previously in voles and suppresses cell proliferation by influencing adrenal steroids. Investigating how estradiol dynamically regulates neurogenesis could provi
J Exp Zool. 2002 Jun 15;293(1):73-80.
Pituitary adenylate cyclase-activating polypeptide induces testicular testosterone synthesis through PGE(2) mediation in crested newt, Triturus carnifex.
Gobbetti A, Zerani M.
Department of Molecular, Cellular and Animal Biology, University of Camerino, Camerino, Italy. anna.gobbettnicam.it
The aim of the present work was to study the possible role of adenylate cyclase-activating polypeptide (PACAP) 38 in the testicular intracellular mechanism regulating steroidogenesis of crested newt, Triturus carnifex. Gonads were incubated in vitro with PACAP 38 and prostaglandin (PG) E(2) alone or with inhibitors of cyclooxygenase (COX), adenylate cyclase (AC), and phospholipase C (PLC) for 30 min and 60 min. PGE(2), PGF(2 alpha), testosterone, and estradiol-17 beta were measured in the culture medium; aromatase (AR) activity and cAMP were assessed in the tissue. PACAP 38 increased PGE(2) (30 min and 60 min), estradiol-17 beta (60 min), cAMP (60 min), and AR (60 min) but decreased testosterone (60 min). PGE(2) increased estradiol-17 beta, cAMP, and AR and decreased testosterone at 30 and 60 min.PLC inhibitor counteracted the effects of PACAP 38, while AC inhibitor counteracted these effects except for PGE(2) increase. AC inhibitor counteracted the effects of PGE(2), while PLC did not. COX inhibitor decreased PGF(2 alpha) (30 min and 60 min), PGE(2) (30 min and 60 min), estradiol-17 beta (60 min), cAMP (60 min), and AR (60 min), but increased testosterone (60 min). These in vitro results suggest that, in newt testis, PACAP 38 acts on PLC, inducing the increase of PGE(2) which, in turn, acting on AC, increases AR activity with the consequent estradiol-17 beta increase and testosterone decrease. Copyright 2002 Wiley-Liss, Inc.
Estradiol has a direct impact on the exocrine pancreas as demonstrated by enzyme and vigilin expression.
Hilgendorf I, Gellersen O, Emmrich J, Mikkat U, Rohwedel J, Krammer HJ, Muller PK, Kruse C.
Department of Medical Molecular Biology, Medical University of Lubeck, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
BACKGROUND: Estrogen receptors have been found in the exocrine pancreas; however, the exact role of estrogen in pancreatic enzyme synthesis and secretion remains to be elucidated. Vigilin, a multi-KH domain protein, is part of a tRNA-containing ribonucleoprotein complex and may be a suitable marker for stimulation of the translational machinery. In the present study, we investigated the influence of estradiol and compared it to CCK on the expression of vigilin, trypsin and amylase in rat pancreatic acini. METHODS: Acini were isolated and incubated with CCK or estradiol. The change in amylase and trypsin levels in the medium and in cell extracts were determined using a photometric method. The change in vigilin mRNA and protein expression were determined by RT-PCR and Western blotting, respectively. RESULTS: Treatment of isolated exocrine pancreatic cells with estradiol caused stimulation of amylase and trypsin production and inhibition of secretion, while treatment with CCK showed only a minor effect on enzyme production and resulted mainly in a stimulation of secretion. Further we found an increase in vigilin mRNA and protein expression in acini stimulated with both CCK-8 and estradiol. CONCLUSION: Our data suggest that estradiol may play a role in inducing exocrine enzyme production but not secretion, and that vigilin, as a marker for translational activity, is stimulated in parallel to the pancreatic enzymes: amylase and trypsin.
Biomed Mater Eng. 2002;12(2):157-67.
Therapeutic effect of in vivo sustained estradiol release from poly (lactide-co-glycolide) microspheres on bone mineral density of osteoporosis rats.
Otsuka M, Uenodan H, Matsuda Y, Mogi T, Ohshima H, Makino K.
Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Motoyama-Kitamachi 4-19-1, Higashi-Nada, Kobe 658-8558, Japan. m-otsukobepharma-u.ac.jp
Poly (lactide-co-glycolide or PLGA) microspheres containing 0.3% (w/w) of estradiol were prepared by a solvent evaporation method. These PLGA microspheres had a wide particle distribution between 0.5 and more than 100 microm. The average size was 76 microm. Physicochemical properties of the microspheres were characterized by X-ray diffraction patterns, FT-IR spectra and DSC. In vitro estradiol release was maintained at a constant rate from these PLGA microspheres for 1 month. The loaded drug was totally recovered in the collection buffer within this time period. In vivo experiments were performed on Wistar rats that had received ovariectomy. These rats were fed with a vitamin D-deficient and Ca-deficient diet. The combination of ovariectomy and diet induced osteoporosis. PLGA microspheres containing either 50, 100, or 200 microg estradiol were injected into these rats. The plasma estradiol in each rat was monitored for 50 days. These in vivo drug release patterns were found to be different from the one obtained from in vitro release. The Ca-AUC was not significant different among various dosages administered. However, bone mineral density for rats after the injection of estradiol loaded microspheres was higher than that obtained for the control. This suggested that all estradiol microspheres administration induced bone generation in osteoporosis rats.
Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats.
Bowman RE, Ferguson D, Luine VN.
Department of Psychology, Hunter College of the City University of New York, 695 Park Avenue, New York, NY 10021, USA. rbowmahiva.hunter.cuny.edu
Twenty-one days of chronic restraint stress impairs male rat performance on the radial arm maze [Luine et al. (1994) Brain Res. 639, 167-170], but enhances female rat performance [Bowman et al. (2001) Brain Res. 904, 279-289]. To assess possible ovarian hormone mechanisms underlying this sexually dimorphic response to stress, we examined chronic stress effects in ovariectomized rats. Ovariectomized rats received Silastic capsule implants containing cholesterol or estradiol and were assigned to a daily restraint stress (21 days, 6 h/day) or non-stress group. Following the stress period, subjects were tested for open field activity and radial arm maze performance. Stress and estradiol treatment affected open field activity. All stressed animals, with or without estradiol treatment, made fewer total outer sector crossings. In contrast, estradiol-treated animals, with or without stress, made more inner sector visits, an indication that estradiol decreased anxious behavior on the open field across time. As measured by the total number of visits required to complete the task, stress did not affect radial arm maze performance in ovariectomized rats, but estradiol-treated animals, with or without stress, performed better than non-treated animals on the radial arm maze. Stressed subjects receiving estradiol showed the best radial arm maze performance. Following killing, tissue samples were obtained from various brain regions known to contribute to learning and memory, and monoamine and metabolite levels were measured. Several changes were observed in response to both stress and estradiol. Most noteworthy, stress treatment decreased ho
Drug Alcohol Depend. 2002 Aug 1;67(3):281-90.
Influence of estrous cycle and estradiol on behavioral sensitization to cocaine in female rats.
Sell SL, Thomas ML, Cunningham KA.
Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77555-1031, USA.
The hypotheses that the estrous cycle and estradiol modulate behavioral sensitization to cocaine in female rats were assessed. In an analysis of sensitization across the estrous cycle, female rats were administered saline or cocaine (15 mg/kg) twice daily for 5 days. Sensitization developed in the intact female rats as measured by the significant increase in stimulant behaviors seen between day 1 and day 5 of treatment. Rats were challenged with cocaine (5 mg/kg) at 3 days following discontinuation of drug treatment. The expression of sensitization as measured between cocaine and saline-treated rats was evident only in female rats in diestus at the time of the challenge test with cocaine. To explore the role of estradiol in sensitization, female rats were ovariectomized or ovariectomized and implanted with estradiol for two weeks prior to treatment with cocaine (15 mg/kg) twice daily for 5 days. Sensitization developed in both ovariectomized and ovariectomized+estradiol rats treated with cocaine as measured by the significant increase in stimulant-like behaviors seen between day 1 and day 5 of treatment. Rats were challenged with 5 mg/kg of cocaine at 3, 13 and 34 days following discontinuation of drug treatment. While neither hormone treatment group exposed to the cocaine regimen expressed sensitization at 3 days of withdrawal, both groups exhibited sensitization at 13 and 34 days following discontinuation of cocaine treatment. The estradiol-treated groups exhibited higher levels of activity relative to their untreated cohorts in both saline or cocaine treatment groups. These results suggest that detection of sensitization in female rats is not only influenced by injection regimen and length of abstinence but
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