Biochem Pharmacol. 2003 Jun 15;65(12):2049-54.
Inhibition of the norepinephrine transporter function in cultured bovine adrenal medullary cells by bisphenol A.

Toyohira Y, Utsunomiya K, Ueno S, Minami K, Uezono Y, Yoshimura R, Tsutsui M, Izumi F, Yanagihara N.

Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan. toyohired.uoeh-u.ac.jp

We report here the effects of an environmental estrogen, bisphenol A, on norepinephrine (NE) transporter function in cultured bovine adrenal medullary cells. The effects of bisphenol A were compared to those of 17beta-estradiol. Bisphenol A significantly inhibited [3H]NE uptake by the cells in a concentration-dependent manner (1-100 microM). Kinetic analysis revealed that bisphenol A, as well as 17beta-estradiol, noncompetitively inhibited [3H]NE uptake. Bisphenol A and 17beta-estradiol inhibited the specific binding of [3H]desipramine to plasma membranes isolated from bovine adrenal medulla. As shown by Scatchard analysis of [3H]desipramine binding, bisphenol A increased the dissociation constant (K(d)) and decreased the maximal binding (B(max)), indicating a mixed type of inhibition. 17beta-Estradiol increased the K(d) without altering the B(max), thereby indicating competitive inhibition. The present findings suggest that bisphenol A inhibits the function of the NE transporter by acting on a site different from that of 17beta-estradiol in the adrenal medulla and probably in the brain noradrenergic neurons.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12787885&dopt=Abstract estradiol




Steroids. 2003 Apr;68(4):373-5.
Short synthesis of 2-methoxyestradiol and 2-hydroxyestradiol.

Kiuru PS, Wahala K.

Department of Chemistry, Organic Chemistry Laboratory, University of Helsinki, A. I. Virtasen aukio 1, P.O. Box 55, FIN-00014 Helsinki, Finland.

The estrogen metabolite 2-methoxyestradiol was synthesized from estradiol bis-THP-ether which was 2-hydroxylated using the superbase LIDAKOR, trimethyl borate, and H(2)O(2), then methylated and deprotected to obtain 2-methoxyestradiol in three steps and 61% yield. 2-Hydroxyestradiol was obtained by deprotecting the 2-hydroxyestradiol bis-THP-ether from the first step.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12787899&dopt=Abstract estradiol




Steroids. 2003 Apr;68(4):383-92.
Metabolism of [6,7-3H, 35S] estradiol 17-sulfate in rats.

Takanashi K, Itoh Y, Watanabe K, Yoshizawa I.

Hokkaido College of Pharmacy, 7-1 Katsuraoka-cho Otaru, Hokkaido 047-0264, Japan.

To confirm whether or not the sulfo group of estradiol 17-sulfate (ES) is removed during in vivo metabolism in rats, the doubly labeled conjugate [6,7-3H, 35S] ES was injected into rats, and its biliary and urinary metabolites were determined by reverse isotope dilution method (RIDM). In male rats, the major radioactivity was detected in biliary disulfate fraction, which was composed of mainly ES and its two minor metabolites, 2-hydroxyestradiol 17-sulfate (2-OH-ES) and 2-methoxyestradiol 17-sulfate (2-MeO-ES). In female rats, in contrast, the radioactivity was dispersed into three fractions:biliary monosulfate, biliary disulfate, and urinary monosulfate fractions (Frs.) In both monosulfate Frs., 7beta-hydroxyestradiol 17-sulfate was detected as the major metabolite followed by 6alpha-, 6beta-, and 15beta-hydroxyestradiol 17-sulfates. Like male rats, 2-OH-ES and 2-Meo-ES as the minor products were detected in biliary disulfate fraction. The isotope ratios of ES and its metabolites in both sexes were essentially the same as that of the dose except that of 6alpha-hydroxylated metabolite, which may be derived from the loss of the tritium labeled at C6. These results confirm the occurrence of the direct metabolism of ES in rats.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12787901&dopt=Abstract estradiol




J Clin Endocrinol Metab. 2003 Jun;88(6):2552-5.
Quantitative determination of estradiol fatty acid esters in lipoprotein fractions in human blood.

Vihma V, Tiitinen A, Ylikorkala O, Tikkanen MJ.

Department of Medicine, University of Helsinki, 00290 Helsinki, Finland.

According to experimental studies, 17 beta-estradiol associates with lipoproteins in blood in the form of fatty acid esters. However, concentrations of endogenous estradiol esters in human lipoprotein fractions have not been previously reported. We investigated the distribution of estradiol fatty acid esters between plasma lipoproteins in 10 healthy women during late pregnancy. Following extraction from serum and ultracentrifugally isolated, gel-filtered lipoproteins, estradiol esters were separated from nonesterified estradiol by column chromatography. After saponification and chromatographic purification of the estradiol ester fraction, the concentration of hydrolyzed esters was determined by estradiol time-resolved fluoroimmunoassay. Of total serum estradiol, a mean of 0.7% (549 pmol/liter, n = 10) was in the form of fatty acid esters. Estradiol fatty acid ester concentrations measured in serum and lipoprotein fraction correlated positively (n = 10; r = 0.98; P < 0.001). The majority of lipoprotein estradiol esters, 54%, was recovered in high-density lipoprotein, and 28% in low-density lipoprotein fraction. Most lipoprotein fractions contained undetectable amounts of nonesterified estradiol (< 36 pmol/liter). In conclusion, our results indicate that estradiol fatty acid esters are mostly bound by lipoproteins in blood in vivo.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12788853&dopt=Abstract estradiol




Am J Physiol Endocrinol Metab. 2003 Jul;285(1):E189-96.
Sex-specific p38 MAP kinase activation following trauma-hemorrhage: involvement of testosterone and estradiol.

Angele MK, Nitsch S, Knoferl MW, Ayala A, Angele P, Schildberg FW, Jauch KW, Chaudry IH.

Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, 35294, USA.

Although immune functions are markedly depressed in males and not in proestrous females following trauma-hemorrhage (T-H), the mechanisms responsible for the divergent responses remain unknown. Because sex steroids modulate the activation of p38, our aim was to determine whether differences in the activation of p38 by phosphorylation (p38-P) might contribute to the sex-dimorphic immune response following T-H. The effects of testosterone and estradiol on the activation of p38 were also examined. Intact male mice (C3H/HeN), castrated males treated with vehicle, 5alpha-dihydrotestosterone (DHT), or 17beta-estradiol, and proestrous females were subjected to trauma (i.e., midline laparotomy) and hemorrhagic shock (35 +/- 5 mmHg for 90 min and resuscitation) or sham operation. At 2 h thereafter, splenic (SMphi) and peritoneal macrophages (PMphi) were harvested and cultured (with 10 microg/ml LPS), and Western blot analysis was carried out for quantification of p38 and p38-P. Sex, testosterone and estradiol plasma levels, and T-H did not alter the constitutive expression of p38 in SMphi and PMphi. In contrast, the activated form of p38 (p38-P) was markedly increased in SMphi and PMphi from female shams compared with male shams. Moreover, the phosphorylation of p38-P increased in males after T-H, whereas it decreased in females under those conditions. Castration before T-H prevented the increase in p38-P in males. Castrated animals treated with DHT displayed increased p38-P following T-H, whereas 17beta-estradiol had no effect on p38-P in castrated mice. Thus 1) sex influences the activation of p38 MAP kinase, 2) DHT is responsible for the increased activation




J Clin Periodontol. 2003 Jun;30(6):556-61.
Modulation of androgen metabolism by phenytoin, oestradiol and tamoxifen in human gingival fibroblasts.

Soory M, Tilakaratne A.

Department of Periodontology, GKT, King's Dental Hospital, London, UK. mena.soorcl.ac.uk

OBJECTIVES: The aim of this investigation is to study androgen metabolism in gingival fibroblasts in response to phenytoin, oestradiol and the antioestrogen tamoxifen, in order to establish the possible role of hormones in the aetiopathogenesis of phenytoin-induced gingival overgrowth. MATERIALS AND METHODS: Six cell lines of human gingival fibroblasts were established in monolayer culture in Eagle's minimum essential medium. Duplicate incubations were performed independently with radiolabelled testosterone and 4-androstenedione, respectively (14C-T/14C-4-A), with optimal concentrations of phenytoin, oestradiol and tamoxifen alone and in combination. At the end of a 24-h incubation period, the medium was solvent extracted for steroid metabolites, which were separated by thin layer chromatography and quantified using a radioisotope scanner. RESULTS: The substrates were metabolised mainly to the diols, 5alpha-dihydrotestosterone (DHT) and 4-androstenedione or testosterone, with the two substrates used. The trends were that phenytoin and oestradiol significantly elevated the yields of the androgens DHT, diols and 4-A/testosterone from both substrates while tamoxifen inhibited the stimulatory effects of oestradiol and phenytoin alone and in combination (n=6; p<0.01, one-way anova). CONCLUSION: Specific hormone-mediated activity in response to phenytoin could contribute to the pathogenesis of gingival overgrowth, which can be decreased by the anti oestrogen tamoxifen.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12795795&dopt=Abstract estradiol




Obstet Gynecol. 2003 Jun;101(6):1177-82.
Serum and follicular fluid cytokines in polycystic ovary syndrome during stimulated cycles.

Amato G, Conte M, Mazziotti G, Lalli E, Vitolo G, Tucker AT, Bellastella A, Carella C, Izzo A.

Institute of Endocrinology, 2nd University of Naples, Naples, Italy. giovanni.amatnina2.it

OBJECTIVE: To investigate the serum and intrafollicular tumor necrosis factor-alpha and interleukin-6 concentrations in infertile women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). METHODS: Thirty-one patients with PCOS undergoing IVF were studied. Thirty-nine normally ovulating women matched for age and body mass index and undergoing IVF for male infertility were the control group. Serum tumor necrosis factor-alpha, interleukin-6, and estradiol levels were assayed before recombinant follicle-stimulating hormone stimulation under gonadotropin-releasing hormone analogue suppression and 34-36 hours after human chorionic gonadotropin (hCG) administration at the time of the oocyte retrieval. Cytokine and estradiol concentrations were also evaluated in the follicular fluids obtained at the time of oocyte retrieval. RESULTS: The patients with PCOS had higher serum and follicular fluid tumor necrosis factor-alpha and interleukin-6 concentrations (P <.001) and lower follicular fluid estradiol levels (P <.05) than control women. In both groups, the serum tumor necrosis factor-alpha, interleukin-6, and estradiol values increased significantly after hCG stimulation. In both groups, the follicular fluid cytokine concentrations were higher than those found in the serum. In the PCOS women the follicular fluid tumor necrosis factor-alpha values were significantly and inversely correlated to the follicular fluid estradiol values (rho = -0.79; P <.001); this correlation was not found in the control subjects. CONCLUSION: In infertile women with PCOS, 1). serum and follicular fluid interleukin-6 and tumor necrosis factor-alpha values were higher than t




Theriogenology. 2003 Mar;59(5-6):1357-71.
The effect of intrauterine administration of estradiol on postpartum uterine involution in cattle.

Sheldon IM, Noakes DE, Rycroft AN, Dobson H.

Department of Veterinary Clinical Science, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts AL9 7TA, UK. msheldovc.ac.uk

In cattle, the first postpartum dominant follicle has a predilection for the ovary contralateral to the previously gravid uterine horn. However, the presence of an estradiol-secreting dominant follicle in the ipsilateral ovary is a marker of subsequent fertility, possibly due to a localized effect of ovarian estradiol on uterine involution. The present study tested the hypothesis that estradiol increases the rate of uterine involution when administered into the previously gravid uterine horn around the expected time of selection of the first postpartum dominant follicle. Dairy cows were treated with 10 mg estradiol benzoate (n=15) or saline (n=14) administered through the cervix into the previously gravid uterine horn lumen on Days 7 and 10 postpartum. Uterine involution was monitored by daily transrectal ultrasonography and estimation of peripheral plasma concentrations of PGFM and acute phase proteins, while ovarian function was monitored by ultrasonography and measurement of plasma hormone concentrations. There was no effect of estradiol treatment on the diameter of the previously gravid or nongravid uterine horns, nor on the plasma concentrations of PGFM or acute phase proteins. However, cows in which the first postpartum dominant follicle ovulated during the study period had a smaller diameter of the previously gravid (P<0.01) or nongravid uterine horns (P<0.001) compared with cows in which the follicle regressed. Thus, our hypothesis was not proven, and the opposite pathway of utero-ovarian signaling may be more important during the postpartum period.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12527082&dopt=Abstract estradiol




J Womens Health (Larchmt). 2003 Apr;12(3):287-98.
The correlations between estradiol, estrone, estriol, progesterone, and sex hormone-binding globulin and anterior cruciate ligament stiffness in healthy, active females.

Romani W, Patrie J, Curl LA, Flaws JA.

Department of Physical Therapy, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. wromanom.umaryland.edu

BACKGROUND: Injury to the anterior cruciate ligament (ACL) often requires surgery and extensive rehabilitation. Women who participate in collegiate sports and military drills are more likely to injure their ACL than are men participating in similar activities. The influence of the normal fluctuation of sex hormones on the physical properties of the ACL is one potential cause for this disparity. The purpose of this study was to report the correlation between estradiol, estrone, estriol, progesterone, and sex hormone binding globulin (SHBG) and ACL stiffness during three phases of the menstrual cycle in normally cycling, healthy females. METHODS: We tested ACL stiffness and collected blood from 20 female subjects who were not using oral contraception during three phases of their menstrual cycle. Ligament stiffness was tested with the KT-2000 trade mark knee arthrometer (MEDmetric, San Diego, CA). Concentrations of estradiol and SHBG were assessed via radioimmunoassay (RIA). Progesterone, estriol, and estrone concentrations were determined via enzyme-linked immunoassay. RESULTS: Spearman rank correlation analysis indicated a significant correlation between estradiol concentration and ACL stiffness (-0.70, p < 0.001) and estrone concentration and ACL stiffness near ovulation (0.46, p = 0.040). With the effects of the other variables controlled, there was a significant partial correlation between estradiol (-0.80, p < 0.001), estriol (0.70, p = 0.003), and progesterone (0.66, p = 0.005) and ACL stiffness near ovulation. CONCLUSIONS: Our results indicate that there is a significant correlation between estradiol, est