J Alzheimers Dis. 2002 Dec;4(6):449-57.
17Alpha-estradiol and 17beta-estradiol treatments are effective in lowering cerebral amyloid-beta levels in AbetaPPSWE transgenic mice.

Levin-Allerhand JA, Lominska CE, Wang J, Smith JD.

The Rockefeller University, New York, NY, USA.

Post-menopausal estrogen therapy is associated with a decreased incidence of Alzheimer disease and in vitro models have shown that 17beta-estradiol is effective in lowering amyloidogenic processing. To examine the effects of estrogen withdrawal and replacement on amyloid beta (Abeta) levels and amyloid beta-protein precursor (AbetaPP) processing in vivo, Swedish mutant AbetaPP transgenic mice were ovariectomized or sham ovariectomized at four weeks of age and treated with placebo or 17beta- or 17alpha-estradiol pellets, the latter being a weak estrogen receptor agonist. Compared to sham ovariectomized mice, ovariectomy with placebo did not alter Abeta levels; however, the levels of Abeta were decreased by 27% and 38% in mice treated with 17beta- and 17alpha- estradiol, respectively, with no change in AbetaPP holoprotein. Endogenous and exogenous estrogen both significantly increased the levels of sAbetaPPalpha, the secreted form of AbetaPP. The ratio of Abeta/sAbetaPPalpha, a measure of amyloidogenic processing, was reduced in all estrogen-containing groups. The Abeta lowering effect of 17beta- and 17alpha-estradiol was replicated when estrogens were administered at a more physiological dose in the drinking water, or when mice were ovariectomized at three months of age. The increased efficacy of 17alpha-estradiol versus 17beta-estradiol may help to develop safe and effective therapeutics.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12515896&dopt=Abstract estradiol




Pharmacology. 2003 Sep;69(1):20-6.
Estradiol relaxes rat aorta via endothelium-dependent and -independent mechanisms.

Abou-Mohamed G, Elmarakby A, Carrier GO, Catravas JD, Caldwell RW, White RE.

Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USA. gaboail.mcg.edu

The effects of estrogen on arterial function are heterogeneous with respect to vessel and/or species. We have investigated 17beta-estradiol-induced relaxation in isolated rat aorta with regard to the role of the vascular endothelium and ionic mechanisms. Estrogen induced a concentration-dependent relaxation of 46.5 +/- 7.9% and 70.1 +/- 12.2% (10(-8) and 10(-7)M), which was reduced by endothelial denudation. Furthermore, L-nitroarginine methyl ester completely abrogated this effect; however, estradiol did not relax KCl-contracted rings. Tetraethyl ammonium (1 mmol/l) completely blocked estradiol-induced relaxation. Estradiol increased [cGMP] in isolated aortic rings via NO, but did not significantly affect NOS activity in endothelial cells. Thus, estrogen can relax rat aorta in vitro via both endothelium-dependent and -independent mechanisms involving the NO/cGMP and potassium channel signaling system. Copyright 2003 S. Karger AG, Basel

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12886026&dopt=Abstract estradiol




Epilepsia. 2003 Aug;44(8):1014-21.
Valproate inhibits the conversion of testosterone to estradiol and acts as an apoptotic agent in growing porcine ovarian follicular cells.

Tauboll E, Gregoraszczuk EL, Kolodziej A, Kajta M, Ropstad E.

Department of Neurology, Rikshospitalet, University of Oslo, Norway. erik.taubollinmed.uio.no

PURPOSE: Long-term valproate (VPA) treatment has been associated with hyperandrogenism and polycystic ovaries in women with epilepsy. The exact mechanisms of action of the drug on sex steroid hormone function are still unsettled. The aim of the present study was to investigate the action of VPA on basal and gonadotropin-stimulated steroid secretion in porcine ovarian follicular cells and to measure the conversion of testosterone to estradiol. Second, the action of VPA on proliferation and apoptosis of follicular cells was investigated. METHODS: Small and medium follicles were obtained from pig ovaries on days 8-10 and 14-16 of the estrus cycle. Both follicular compartments, theca and granulosa cells, were cultured as a coculture resembling follicles in vivo. VPA in concentrations of 100 and 250 micrg/ml was added to the control or gonadotropin-stimulated cultures. RESULTS: VPA caused a significant increase in basal and luteinizing hormone (LH)-stimulated testosterone secretion from small follicles, whereas in medium follicles, an increased basal but decreased LH-stimulated testosterone secretion was found. VPA caused decreased basal and follicle-stimulating hormone (FSH)-stimulated estradiol secretion by small follicles, whereas only the higher concentration decreased estradiol secretion in medium follicles. The conversion of testosterone to estradiol by small follicles was decreased under the influence of VPA in testosterone-alone and in testosterone-plus-FSH-stimulated cultures, whereas this was seen at only the higher VPA concentration in medium follicles. VPA had no effect on cell proliferation and viability, whereas in a dose-dependent manner, VPA increa




Biol Reprod. 2003 Dec;69(6):1793-800. Epub 2003 Jul 30.
Exposure of bovine oocytes to the endogenous metabolite 2-methoxyestradiol during in vitro maturation inhibits early embryonic development.

Lattanzi ML, Santos CB, Mudry MD, Baranao JL.

Instituto de Biologia y Medicina Experimental, Departamento de Ecologia, Genetica y Evolucion, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina.

Catecholestrogens are endogenous metabolites that have been shown to modulate granulosa, theca, and luteal cell function in some species. The present study was aimed at determining the possible role of these steroids on oocyte maturation. Cumulus-enclosed bovine oocytes were matured for 24 h, fertilized, and then cultured for 8 days. Whereas estradiol was without effect, addition of catecholestrogens (2-hydroxyestradiol, 4-hydroxyestradiol, and 2-methoxyestradiol [2-MOE2]) to the maturation medium did not affect the cleavage rate but was associated with a decrease in blastocyst production on Day 8. Although 2-MOE2 was also able to inhibit blastocyst formation when added during embryo culture, the effects were less pronounced than those seen when the steroid was added only during maturation. In agreement with the known ability of 2-MOE2 to bind tubulin at the colchicine site, marked alterations were observed in the spindle assembly of oocytes exposed to 2-MOE2 during maturation, which lead to gross chromosomal aberrations after fertilization and consequent developmental arrest at the morula stage. Moreover, that the blastocyst rate was not affected when meiosis was blocked with roscovitine during 2-MOE2 exposure is consistent with the idea that altered nuclear maturation is the cause of the low developmental competence. Because 2-MOE2 could be increased in follicular fluid in response to aryl hydrocarbon-receptor ligands, such as some environmental contaminants, our results show that abnormally high intraovarian levels of catecholestrogens could have a deleterious effect on ooc




J Reprod Immunol. 2003 Jun;59(1):17-28.
17 beta-estradiol induces L-type Ca2+ channel activation and regulates redox function in macrophages.

Azenabor AA, Chaudhry AU.

Department of Health Sciences, Enderis Hall, Room 469, University of Wisconsin, 2400 East Hartford Avenue, Milwaukee, WI 53211, USA. aazenabwm.edu

17 beta-estradiol induces rapid effects on cells of the immune system via plasma membrane surface receptor but the ways in which delayed signals involving intracellular receptors affect the same functions are not well understood. To study the delayed but sustained events in estradiol signaling, we have investigated macrophage Ca(2+) signaling, detected specific Ca(2+) ion channel activated and found a relationship between intracellular calcium [Ca(2+)](i) and macrophage release of reactive oxygen species (ROS) and nitric oxide (NO) during delayed 17 beta-estradiol activity. We found evidence of additional effect of estradiol on capacitative entry of Ca(2+), Ca(2+) entry through L-type channel and a direct relationship between [Ca(2+)](i) and generation of ROS and NO. This study demonstrates that 17 beta-estradiol exhibits a delayed phase of Ca(2+) influx involving L-type channel and regulates macrophage immune redox function.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12892900&dopt=Abstract estradiol




J Pharmacol Exp Ther. 2003 Oct;307(1):395-401. Epub 2003 Jul 31.
17Beta-estradiol as a receptor-mediated cardioprotective agent.

Booth EA, Marchesi M, Kilbourne EJ, Lucchesi BR.

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0632, USA.

Cardiac tissue that undergoes an ischemic episode exhibits irreversible alterations that become more extensive upon reperfusion. Estrogen treatment has been reported to protect against reperfusion injury, but the mechanism remains unknown. The cardioprotective effects of 17beta-estradiol, a biologically active form of the hormone, and 17alpha-estradiol were assessed in an in vivo occlusion-reperfusion model. Anesthetized, ovariectomized rabbits were administered 17beta-estradiol (20 microg), 17alpha-estradiol (1 mg), or vehicle intravenously 30 min before a 30-min occlusion of the left anterior descending (LAD) coronary artery followed by 4 h of reperfusion. Infarct size as a percentage of area at risk decreased in the 17beta-estradiol-treated group (18.8 +/- 1.7) compared with 17alpha-estradiol (41.9 +/- 4.8; P < 0.01) or vehicle groups (48 +/- 5.5; P < 0.001). Similar results were obtained when infarct size was expressed as a percentage of total left ventricle. The second objective of the study was to assess fulvestrant (Faslodex, ICI 182,780), an estrogen receptor antagonist, for its effects on infarct size in ovariectomized female rabbits treated with 17beta-estradiol. ICI 182,780 was administered intravenously 1 h before the administration of 17beta-estradiol (20 microg) or vehicle. The hearts were subjected to 30-min LAD coronary artery occlusion and 4 h of reperfusion. Pretreatment with ICI 182,780 significantly limited the infarct size sparing effect of 17beta-estradiol when expressed as a percentage of the risk region (53.0 +/- 5.0). The results indicate that 17beta-estradiol protects the heart against ischemia-reperfusion injury and that the observed cardioprotection is mediated by the estrogen receptor.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12893838&dopt=Abstract estradiol [P




J Neuroendocrinol. 2003 Sep;15(9):855-64.
Immunocytochemical detection of progesterone receptor in the female rabbit forebrain: distribution and regulation by oestradiol and progesterone.

Caba M, Rovirosa MJ, Beyer C, Gonzalez-Mariscal G.

Laboratorio de Biologia de la Reproduccion, IIB, Universidad Veracruzana, Xalapa, Mexico.

There is no information on the neuroanatomical distribution of the progesterone receptor (PR) in the rabbit. Therefore, we mapped the distribution of PR-immunoreactive cells in the forebrain of ovariectomized female rabbits. Vehicle-injected ovariectomized rabbits showed PR-immunoreactive cells only in the infundibular nucleus (IN) and nucleus X (lateral to the ventromedial hypothalamic nucleus). The injection of oestradiol benzoate (EB; 5 micro g/day for 5 days) increased the number of PR-immunoreactive cells in the IN and in three nuclei of the preoptic region (periventricular, medial, and principal). Abundant PR were also found in the paraventricular nucleus and nucleus X. Administration of progesterone (10 mg/day) for 3 days to EB-treated rabbits (a treatment that induces digging behaviour for the maternal nest and suppresses sexual receptivity and scent-marking) eliminated PR-immunoreactivity from all brain areas analysed except the IN. Thus, one-third of the number of cells seen in the ovariectomized + EB condition persisted in this region despite progesterone injections. Withdrawal of progesterone (and continuation of EB) for 5 (but not for 2) days (in a schedule similar to the one that induces straw-carrying and hair-pulling for the maternal nest) increased the number of PR-immunoreactive cells in all regions analysed. These results show that restricted regions of the female rabbit forebrain express abundant PR which are either: (i). up-regulated by oestradiol and down-regulated by progesterone; (ii). oestradiol-insensitive and down-regulated by progesterone; or (iii). insensitive to both oestradiol and progesterone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12899680&dopt=Abstract estradiol [PubMed - indexed for M




Environ Toxicol. 2003 Aug;18(4):211-8.
Effects of 17alpha-ethinylestradiol on immune parameters in the lizard Sceloporus occidentalis.

Burnham DK, Lackey A, Manering M, Jaensson E, Pearson J, Tyler DO, Melson D, Talent LG.

Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, OK 74078, USA. burnhakstate.edu

We examined the effect of 17alpha-ethinylestradiol on immunity of the Western fence lizard, Sceloporus occidentalis. Injection of 17alpha-ethinylestradiol resulted in dose-dependent suppression of peripheral blood leukocyte levels as determined by cell counts, whereas total spleen cell levels were decreased only at higher doses of 17alpha-ethinylestradiol. In contrast, spleen cell proliferation was enhanced by 17alpha-ethinylestradiol as measured by reduction of MTT to formazan following a two-way mixed lymphocyte reaction. Antibody responses were unaffected. Effects on peripheral blood leukocyte levels and spleen cell proliferation similar to those observed in response to injection of 17alpha-ethinylestradiol were observed following injection of a single dose of hydrocortisone. However, injection of lizards with 17alpha-ethinylestradiol did not result in a significant increase in serum cortisol. Results of this study suggest that exposure of Western fence lizards to 17alpha-ethinylestradiol leads to decreased numbers of circulating leukocytes and total spleen cell numbers and the enhancement of spleen cell proliferation in a two-way mixed lymphocyte reaction. These effects probably involve mechanisms other than or in addition to the induction of cortisol release. Copyright 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 211-218, 2003.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12900939&dopt=Abstract estradiol




Environ Geochem Health. 2003 Mar;25(1):63-7.
Sorption of the natural endocrine disruptors, oestrone and 17 beta-oestradiol in the aquatic environment.

Bowman JC, Readman JW, Zhou JL.

Centre for Environmental Research, School of Chemistry, Physics and Environmental Science, University of Sussex, Falmer, BN1 9QJ, Brighton, UK.

Adsorption of hydrophobic contaminants at the particle/water interface is one of the key processes controlling their fate in the aquatic environment. The sorption of the natural female hormones oestrone and 17 beta-oestradiol has been studied under simulated riverine conditions. Both the kinetics and the effects of varying fundamental environmental parameters (e.g. sediment properties) on the thermodynamic equilibrium partition coefficient (Kp) have been studied in continuous and batch sorption experiments, respectively. Results showed that the sorption of oestrone and 17 beta-oestradiol by sediment was relatively slow, reaching equilibrium in 50 days. In addition, relatively small adsorption of both oestrone and 17 beta-oestradiol onto the sediment was observed, with Kp values between 200 and 250 mL g-1. The comparable Kp values of the two compounds reflect their structural similarity. It can be concluded that the two endocrine disruptors, oestrone and 17 beta-oestradiol remain primarily in association with the aqueous phase.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12901080&dopt=Abstract estradiol