Oncol Rep. 2002 Jul-Aug;9(4):773-6.
Oestrogen causes G2/M arrest and apoptosis in breast cancer cells MDA-MB-231.

Nomoto S, Arao Y, Horiguchi H, Ikeda K, Kayama F.

Department of Health Science, Jichi Medical School, Minamikawachi, Kawachi-gun, Tochigi 329-0498, Japan. nomotichi.ac.jp

Flavonoids have been shown to exert many biological activities within cancer cells, and oestrogen is known to be structurally related to flavonoids. We investigated the effects of oestrogen in cancer cells to determine if its activities would be similar to those of flavonoids. When 50 microM 17 beta-oestradiol (oestradiol) was added to the oestrogen receptor (ER) alpha-negative breast cancer cell line MDA-MB-231, growth arrest was apparent, similar to that observed with genistein and daidzein. Oestradiol exhibited a dose response curve for the growth arrest similar to those of genistein and daidzein. Apoptosis occurred in the breast cancer cells after treatment with 50 microM oestradiol, genistein, or daidzein, with similar profiles. Flow cytometry analysis revealed that oestradiol treatment caused G2/M arrest and apoptosis. Cell-cycle arrest at G2/M began at 6 h after treatment, and apoptosis began within 24 h. Because MDA-MB-231 cells are ER alpha negative, these results suggest that oestradiol induces cell-cycle arrest and apoptosis through an ER alpha-independent pathway.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12066207&dopt=Abstract estradiol




Theriogenology. 2002 May;57(8):1957-72.
Comparisons of estradiol, LH and FSH patterns in pregnant and nonpregnant beagle bitches.

Onclin K, Murphy B, Verstegen JP.

Department of Clinical Sciences, Veterinary College, University of Liege, Belgium. k.onclilg.ac.be

To characterize plasma estradiol, LH and FSH patterns of secretion during the bitch estrous cycle, blood samples were obtained daily from 15 days before until 135 days after the LH surge in 10 pregnant and 10 nonpregnant beagle bitches. After an initial increase between days 15 and 10 and an expected proestrous peak, estradiol concentrations increased again from days 9-12 (corresponding to cytological metestrus) from basal values observed around day 9 after the LH surge, and remained significantly elevated throughout the luteal phase both in pregnant and nonpregnant animals. Concomitantly with the end of the luteal phase, plasma concentrations of estradiol returned to basal values in both groups. During the mid- to late-luteal phase, mean basal LH secretion was significantly elevated throughout in the pregnant relative to the nonpregnant animals. However, in nonpregnant animals, pulsatility was increased and peaks of higher amplitude were observed. The plasma FSH profiles, determined by a specific homologous RIA, differed significantly between pregnant and nonpregnant bitches during the last two-thirds of the luteal phase with a mean FSH level more elevated during pregnancy. The FSH level then decreased around parturition and low concentrations during lactation period were observed. The FSH concentrations remained steady in nonpregnant luteal phases from early luteal phase through mid-anestrus. The differences in pregnant and nonpregnant LH and FSH concentrations suggest pregnancy differences in regulation of the corpus luteum. Finally, the elevated estradiol concentrations observed during the luteal phase of both pregnant and nonpregnant animals suggest that an ovarian production of estrogens may be involved in overall corpus lu



Pharmacol Toxicol. 2002 Mar;90(3):121-6.
Effects of epomediol on ethinyloestradiol-induced changes in glutathione homeostasis in the rat.

Cuevas MJ, Almar M, Gonzalez-Gallego J.

Department of Physiology, University of Leon, Spain. dfimcnileon.es

Epomediol is a synthetic terpenoid compound that has been reported to reduce ethinyloestradiol-induced cholestasis. The choleretic action of epomediol is related to an increase in both the bile acid-dependent and independent fractions of bile flow, but the role of glutathione metabolism and transport is still unknown. This study was aimed to evaluate if changes in glutathione homeostasis could contribute to the beneficial effects of epomediol in rats with ethinyloestradiol-induced cholestasis. When compared to control animals, ethinyloestradiol treatment resulted in a significant decrease in the liver concentration of reduced (GSH) and oxidized glutathione. Both GSH and oxidized glutathione concentrations returned to normal in animals receiving ethinyloestradiol plus epomediol. Ethinyloestradiol administration induced a significant decrease in plasma and renal GSH and the tripeptide was almost absent from bile. Combined treatment with epomediol plus ethinyloestradiol normalised renal GSH and both biliary and liver cysteine were significantly increased. Liver and kidney gamma-glutamyltranspeptidase activities were higher in rats receiving ethinyloestradiol and still remained elevated in animals with the combined treatment. Liver gamma-glutamylcysteine synthetase activity rose significantly by administration of ethinyloestradiol plus epomediol but the corresponding mRNA levels were not modified. Changes in glutathione homeostasis and higher biliary levels of GSH amino acid constituents could contribute to the beneficial effects of epomediol in rats with ethinyloestradiol-induced cholestasis.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12071332&dopt=Abstract estradiol




J Med Assoc Thai. 2002 Jan;85(1):58-62.
Serum estradiol and follicle-stimulating hormone levels in Thai women post total abdominal hysterectomy and bilateral oophorectomy using oral 17 beta-estradiol.

Bunyavejchevin S, Panthong C, Limpaphayom KK.

Department of Obstetrics & Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

OBJECTIVE: To assess the difference of serum estradiol (E2) and follicle stimulating hormone (FSH) levels in Thai women post total abdominal hysterectomy and bilateral oophorectomy, before and after using a daily dose of 2 mg oral 17 beta-estradiol. STUDY DESIGN: Experimental study (before and after treatment). SETTING: Menopause Clinic, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University. SUBJECTS: Thirty-five women who had undergone total abdominal hysterectomy and bilateral oophorectomy at Chulalongkorn Hospital 1 week previously due to benign gynecologic conditions were recruited in the study. Body mass index was 20-25 kg/m2. These women had no contraindication for using hormonal replacement therapy and no history of any hormonal intake in the past. INTERVENTION: All subjects were assigned to receive a daily dose of 2 mg oral 17 beta-estradiol applied at bedtime (8.00 p.m.). MAIN OUTCOME MEASURES: Serum E2 and FSH were measured before and after the study at weeks 4, 8 and 12, 12-14 hours after oral application. The hormonal measurement was performed using the time-resolved fluoroimmunoassay (FIA) method. RESULTS: Five cases were excluded, three cases due to poor compliance which was less than 85 per cent and two cases due to loss to follow-up. Of the remaining 30 cases, the mean age and body mass index were 43.03 +/- 4.58 years and 22.72 + 1.86 kg/m2, respectively. Serum E2 level significantly increased from baseline value at 4, 8 and 12 weeks (median of E2 value at 0, 4, 8 and 12 weeks: 20.00, 22.50, 324.65 and 355.35 pmol/L, p<0.001). On the other hand, there was no significant difference in the FS




Bioorg Khim. 2002 May-Jun;28(3):236-41.
[Molecular model of binding of estradiol and 8-isoestradiol with estrogen alpha-receptor]

[Article in Russian]

Shavva AG, Vlasova KV, Tsogoeva SB, Egorov MS, Iakutseni PP.

Chemical Faculty, St. Petersburg State University, Universitetskii pr. 26, Staryi Petergof, St. Petersburg, 198504 Russia. nmaloma.spbu.ru

The complexes of the estrogen alpha-receptor with estradiol and 8-isoestradiol were comparatively analyzed. The computations of ligand-receptor complexes, carried out using the FLEXX program, allowed us to propose a model for the binding of the analogues of 8-isoestradiol. It was found that rings C and D of estradiol and 8-isoestradiol are similarly arranged in the ligand-binding pocket and coincide upon the superposition of the corresponding ligand-receptor complexes, whereas rings A and B do not coincide. The oxygen functions in position 17 of the estradiol analogues of both series coincide upon superposition, whereas the phenol 3-hydroxyl groups are 0.05 A apart. A comparison of the predicted biological properties of modified estradiol analogues of the natural and 8-isoseries with the available experimental data revealed their similarity. Synthetic 2-acetyl analogues of 8-isoestrogens were found to have no uterotropic activity, which is also consistent with the proposed model.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12077849&dopt=Abstract estradiol




Biol Reprod. 2002 Jul;67(1):119-25.
Progesterone blocks the estradiol-stimulated luteinizing hormone surge by disrupting activation in response to a stimulatory estradiol signal in the ewe.

Richter TA, Robinson JE, Evans NP.

Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge CB2 4AT, UK.

The preovulatory surges of GnRH and LH are activated by increased concentrations of circulating estradiol, but ovulation is blocked when progesterone concentrations are elevated. Although it is has been shown that this action of progesterone is due to a central inhibition of the GnRH surge, the mechanisms that underlie the blockade of the GnRH surge are poorly understood. In this study we investigated whether progesterone can block the estradiol-dependent activation stage of the GnRH surge induction process, and thus prevent expression of the LH surge. The results demonstrated that exposure to progesterone for half or the full duration of the activation stage can prevent the stimulation of LH surges by estradiol (experiment 1), whereas exposure to progesterone midway though a period of estradiol exposure, which in itself is sufficient to activate the surge, did not block the LH surge (experiment 2). These results suggest that progesterone 1) disrupts activation of the surge induction system in response to a stimulatory estradiol signal and 2) does not compromise the ability of animals to respond to a stimulatory estradiol signal applied immediately after progesterone exposure. Because the disruptive effects of activated progesterone in response to estradiol are rapid but transient, it may be that progesterone directly interferes with the activation of estradiol-responsive neural systems to block the GnRH/LH surge.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12080007&dopt=Abstract estradiol




Biol Pharm Bull. 2002 Jun;25(6):738-42.
Effects of osthole on postmenopausal osteoporosis using ovariectomized rats; comparison to the effects of estradiol.

Li XX, Hara I, Matsumiya T.

Department of Pharmacology, Intractable Diseases Research Center, Tokyo Medical University, Japan. xiaoxialail.goo.ne.jp

The purpose of this study was to examine effects of osthole on postmenopausal osteoporosis using ovariectomized (OVX) rats. All of the rats were divided into sham and OVX groups. At 2 weeks post-operation, the sham-operated rats received solvent vehicle (97% corn oil and 3% ethanol, 1.0 ml/kg, subcutaneously); the OVX rats were divided into three groups which were treated with solvent vehicle (same the sham rats, 1.0 ml/kg, subcutaneously), 17beta-estradiol (30 microg/kg, subcutaneously) or osthole (9.0 mg/kg, orally) 5 d/week for 4 weeks, respectively. In OVX rats, the increases of body weight, spleen and thymus weight were significantly decreased and the atrophy of uterus was preserved by 17beta-estradiol treatment, but not by osthole. Treatment with either 17beta-estradiol or osthole significantly protected cancellous bone loss owing to estrogen deficiency and significantly increased the maximal load in the femoral neck of OVX rats. In addition, the increases of serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) levels caused by ovariectomy were all significantly suppressed by 17beta-estradiol. However, only urinary DPD was significantly reduced by osthole and no change was found in serum OC. Our results demonstrate that osthole may be just as effective as 17beta-estradiol in suppressing bone loss due to ovariectomy but osthole perhaps does not work through the estrogen pathway.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12081139&dopt=Abstract estradiol




J Physiol. 2003 Jun 1;549(Pt 2):573-81. Epub 2003 Apr 17.
Central nervous system prostaglandin endoperoxide synthase-1 and -2 responses to oestradiol and cerebral hypoperfusion in late-gestation fetal sheep.

Wood CE, Giroux D.

Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL 32610, USA. cwoohys.med.ufl.edu

Previous work in this laboratory has demonstrated that cerebral hypoperfusion increases the expression of prostaglandin endoperoxide synthase-2 (PGHS-2) in ovine fetal brain regions. Endogenously produced prostaglandins, in turn, partially mediate the fetal hypothalamus- pituitary-adrenal (HPA) axis response to arterial hypotension. In separate experiments, we have found that oestradiol stimulates fetal HPA axis activity. The present experiments were designed to test the hypothesis that oestradiol increases the expression of PGHS isoforms, and that oestradiol augments the PGHS response to cerebral hypoperfusion. Sixteen fetal sheep of known gestational ages (124-128 days' gestation at the time of study) were subjected to chronic catheterization and implantation of extravascular occluder around the brachiocephalic artery. Eight fetuses were subjected to subcutaneous implantation of a pellet containing 17beta-oestradiol (release rate 5 mg (21 days)-1). Brachiocephalic occlusion (BCO) stimulated adrenocorticotropin (ACTH), cortisol and arginine vasopressin (AVP) secretion, responses that were augmented by oestradiol. One hour after the beginning of a 10 min period of BCO, PGHS-1 mRNA was increased in fetal brainstem and hypothalamus, and PGHS-2 mRNA was increased in fetal brainstem. Oestradiol, by itself, increased the abundance of PGHS-2 mRNA in brainstem and cerebellum, and augmented the PGHS-2 mRNA response to BCO in brainstem. In contrast, oestradiol had no significant effect on the abundance of PGHS-1 mRNA in any brain region. PGHS-1 and PGHS-2 protein levels did not reflect the changes in the respective mRNAs. The abundance of both proteins




Methods Find Exp Clin Pharmacol. 2002 Apr;24(3):125-30.
Testosterone and estradiol modulate TNF-alpha-induced expression of adhesion molecules in endothelial cells.

Zhang X, Wang L, Dou Y, Zhao J, Jiang T, Qiao Z, Qiao J.

Laboratory of Molecular Biology, Shanxi Medical University, Taiyuan, P.R. China.

Cytokine-activated endothelial expression of adhesion molecules plays an important role in immune responses. In the present study, we investigated the influences of testosterone and 17 beta-estradiol on tumor necrosis factor-alpha (TNF-alpha)-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVEC). HUVEC were incubated with TNF-alpha, testosterone or 17 beta-estradiol separately, or in a combination of TNF-alpha plus testosterone or 17 beta-estradiol. The expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was evaluated at 3, 6, 12 and 24 h following exposure by flow cytometric analysis. The results showed that although testosterone or 17 beta-estradiol did not affect the expression of these adhesion molecules in unstimulated HUVEC, both of them transiently increased the expression of E-selectin and VCAM-1 in TNF-alpha stimulated HUVEC. Neither testosterone nor 17 beta-estradiol affected the expression of ICAM-1 induced by TNF-alpha. It is concluded that both testosterone and 17 beta-estradiol increase TNF-alpha-induced expression of E-selectin and VCAM-1 in endothelial cells and these facts might indicate a mechanism by which gonadal hormones can indirectly enhance immune responses.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12087872&dopt=Abstract estradiol