Hum Reprod. 2003 Oct;18(10):2048-51.
GnRH antagonists followed by a decline in serum estradiol results in adverse outcomes in donor oocyte cycles.

Lindheim SR, Morales AJ.

Fertility Specialist Medical Group, San Diego, California, USA.

BACKGROUND: The aim of this retrospective study was to assess clinical outcomes using GnRH antagonists in oocyte donation cycles. METHODS: Between July 2000 and June 2001, 40 recipient cycles generated from donor oocytes were evaluated. Controlled ovarian hyperstimulation (COH) was started on cycle day 2 using recombinant gonadotrophins (225 IU daily). GnRH antagonist was started on cycle day 6 of COH. All recipients were synchronized to donors using GnRH agonist followed by estrogen and progesterone supplementation. Main outcome measures were days of stimulation (DOS), number of ampoules used, peak serum estradiol, number of oocytes, fertilization rate, embryo score, clinical on-going pregnancy rate and implantation rate. RESULTS: Thirty-seven donor cycles (93%) underwent oocyte retrieval, resulting in 36 embryo transfers. Fourteen cycles (35%) had decreased serum estradiol after initiation of GnRH antagonist. No differences were seen in numbers of FSH ampoules, DOS, peak serum estradiol, number of retrieved oocytes, fertilization rate and embryo quality. However, clinical pregnancy rate per initiated cycle [14% (2/14) versus 54% (14/26)], ongoing pregnancy rate per initiated cycle [7% (1/14) versus 46% (12/26)] and implantation rate (4 versus 24%) were all significantly less (P <0.05) following a decrease in serum estradiol after initiation of GnRH antagonist. No clinical predictor, including donor age, basal day 2 FSH or estradiol, ovarian morphology or serum estradiol prior to GnRH antagonist, was predictive of a decline in serum estradiol following GnRH antagonist. CONCLUSION: These data demonstrate an adverse effect on clinical outcome in cycles, resulting in a decline in serum estradiol after GnRH antagonist administration. This effect was unpred




Hum Reprod. 2003 Oct;18(10):2137-44.
17Beta-estradiol and progesterone improve in-vitro cytoplasmic maturation of oocytes from unstimulated prepubertal and adult rhesus monkeys.

Zheng P, Si W, Bavister BD, Yang J, Ding C, Ji W.

Department of Primate Biology, China-US Primate Biology Laboratory, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 Jiao Chang Dong Lu, Kunming 650223, China.

BACKGROUND: Effects of 17beta-estradiol and progesterone on rhesus monkey oocyte maturation in vitro were evaluated by embryo development subsequent to IVF. METHODS AND RESULTS: In experiment 1, immature cumulus-oocyte complexes collected from unstimulated adult females during the non-breeding season were matured in modified medium CMRL-1066 containing various combinations of gonadotrophins (FSH + LH), estradiol and/or progesterone. Formation of morulae and blastocysts was greatest in oocytes matured in medium containing estradiol and/or progesterone, with or without gonadotrophins (morula 38-46%, blastocyst 14-20%) than in control oocytes matured without estradiol or progesterone (morula 14%, blastocyst 0%). In experiment 2, cumulus-oocyte complexes from unstimulated prepubertal female monkeys were matured in medium with gonadotrophins, estradiol or progesterone. The best development to the morula stage was obtained with oocytes matured with gonadotrophins and estradiol or gonadotrophins and progesterone (43 and 25 morulae, respectively), while control oocytes matured with gonadotrophins but without steroid hormones gave the poorest morula developmental response (12%). However, there was no difference in blastocyst development across all groups (0-3%). CONCLUSIONS: These results demonstrate that during rhesus monkey oocyte maturation in vitro: (i) estradiol or progesterone can improve oocyte developmental competence; (ii) immature oocytes from prepubertal versus adult females have differential responses to challenge with estradiol or progesterone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14507835&dopt=Abstract estradiol [PubMed - indexed for ME




Clin Endocrinol (Oxf). 2003 Oct;59(4):482-6.
The gender differences in growth hormone-binding protein and leptin persist in 80-year-old men and women and is not caused by sex hormones.

Bulow B, Ahren B, Fisker S, Dehlin O, Hagberg B, Jensen E, Svensson T, Samuelsson G, Erfurth EM.

Department of Medicine, Lund University, Lund, Sweden. b.buloelia.com

OBJECTIVE: Leptin and growth hormone-binding protein (GHBP) both show gender differences that might be explained by sex hormones. To study the potential relevance of oestradiol and testosterone, we have examined 80-year-old subjects in whom oestradiol is higher in men than in women. The interrelationships between leptin, insulin, GHBP and fat mass in this age group were also investigated. DESIGN AND SUBJECTS: Ninety-four subjects (55 females and 39 males), all 80 years old, were investigated in a community-based study. None of the investigated subjects was being treated for diabetes mellitus and none of the women had oestrogen replacement. METHODS: Levels of testosterone, oestradiol, SHBG, IGF-I, GHBP, glucose, insulin and leptin were analysed. Body composition was measured with bioimpedance analysis (BIA). RESULTS: As in younger age groups, serum leptin, the ratio leptin/kilogram fat mass and serum GHBP were higher in the women (all, P< or =0.007), although serum oestradiol was higher in the men (P<0.001). There were no significant associations between sex hormones and leptin or GHBP either in women or in men (all, r<0.13, P>0.1). Leptin correlated to kilogram fat mass in both women (r=0.55, P<0.001) and men (r=0.47, P=0.003), but in contrast, there were no significant correlations between GHBP and fat mass and GHBP and IGF-I, either in women or in men (all, r<0.24, P>0.2). Insulin and leptin were significantly associated with GHBP, both in women (r=0.48, P<0.001 and r=0.43, P=0.001, respectively) and in men (r=0.40, P=0.01 and r=0.34, P=0.03, respectively). CONCLUSIONS: Although the 80-year-old men had higher oestradiol l




Angiogenesis. 1999;3(3):271-80.
Estradiol enhances endothelial cell interactions with extracellular matrix proteins via an increase in integrin expression and function.

Cid MC, Esparza J, Schnaper HW, Juan M, Yague J, Grant DS, Urbano-Marquez A, Hoffman GS, Kleinman HK.

Department of Internal Medicine, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune diseases involving blood vessels than men. Although the precise effects of estrogens on the cardiovascular system are largely unknown, recent data suggest that estrogens can exert direct regulatory effects on endothelial cells. In the present study, we show that 17beta-estradiol increases human umbilical vein endothelial cell attachment to the extracellular matrix proteins laminin-1, type IV collagen, type I collagen, and fibronectin. Estradiol enhanced adhesion most significantly to laminin-1 and to fibronectin-derived synthetic peptides containing an RGD sequence. Upon exposure to estradiol, an increase in beta1, alpha5 and alpha6 integrin mRNA was observed in subconfluent cells which was abrogated by treatment with cycloheximide. This increase was followed by a later enhancement in surface expression of the above integrins. In addition, integrin-mediated signaling was also enhanced by estrogens since an increase in tyrosine-phosphorylation of focal adhesion kinase induced by cell attachment was observed in estrogen-treated endothelial cells. Since integrins have an important role in mediating endothelial cell attachment, migration and differentiation, the increase in integrin expression and function induced by estradiol may be an important mechanism through which estrogens can promote neovascularization and vessel repair.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14517426&dopt=Abstract estradiol [PubMed]




Horm Metab Res. 2003 Sep;35(9):527-31.
Effects of triiodothyronine and estrogen administration on bone mass, mineral content and bone strength in male rats.

Broulik PD, Rosenkrancova J, Ruzicka P, Sedlacek R.

Third Medical Clinic, First Medical Faculty, Charles University, Prague, Czech Republic. pbrofl.cuni.cz

Experimental hyperthyroidism had a negative effect on bone mineral density, but did not significantly alter mechanical properties of femur and femoral bone thickness. Estradiol at a dose used in humans for the treatment of osteoporosis decreased seminal vesicle weight and concentration of testosterone but increased bone density in male rats compared to intact animals. In these rats, the mechanical analysis revealed an increased mechanical femur strength higher than the increase in bone density and femoral cortical thickness. When hyperthyroid male rats with low bone density were treated with estradiol in spite of a low plasma testosterone, the changes in bone density resulting from hyperthyroidism were entirely prevented. Estrogens protect the male skeleton against resorbing action of T (3). Treatment with estradiol in male rats with hyperthyroidism did not increase mechanical bone strength or femoral cortical thickness as it did with estradiol administration alone. Our results suggest that exogenously administered estrogens may have therapeutic value in preventing bone loss accompanying triiodothyronine administration, even in male rats with a low testosterone levels. At the concentration studied, estradiol increased in spite of low plasma testosterone, bone mineral density, mechanical strength of femur, and femoral cortical thickness.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14517768&dopt=Abstract estradiol




Theriogenology. 2003 Nov;60(8):1423-34.
Suppression of circulating concentrations of FSH and LH by inhibin and estradiol during the initiation of follicle deviation in mares.

Donadeu FX, Ginther OJ.

Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison, 1656 Linden Drive, Madison, WI 53706, USA.

The role of estradiol and inhibin in suppression of FSH and LH during the initiation of follicle deviation was examined in mares. In Experiment 1, the two largest follicles (F1, F2) were retained during a wave and the rest were ablated as they reached > or =10 mm. The largest follicle was left intact (control, n=12) or was ablated when it reached > or =20.0 mm (Day 0; expected beginning of deviation). The second largest follicle continued growing (n=9) or regressed (n=4) after F1 ablation. Circulating estradiol and total inhibin decreased after Day 0 in the F2-regressing group, whereas estradiol increased after Day 0.5 and inhibin was unaltered in the control and F2-growing groups. Circulating FSH decreased in the control group and increased in the F2-regressing group after Day 0. In the F2-growing group, FSH increased between Days 0 and 0.5 and then decreased. Circulating LH increased between Days 0 and 2 in the F2-regressing group and between Days 0 and 0.5 in the F2-growing group. In Experiment 2, 0 or 1 follicle was retained in a wave followed by administration of 0 or 1 mg of estradiol at the expected beginning of deviation (Hour 0; 2 x 2 factorial design, n=4-6/group). Circulating total inhibin was higher and FSH was lower at Hour 0 in the 1-follicle than in the 0-follicle groups. Follicle-stimulating hormone decreased after Hour 0 in the 1-mg but not in the 0-mg groups, and the decrease in the 0-follicle/1-mg group was not to the level of that in the 1-follicle/1-mg group. Circulating LH was not affected by follicle number but was reduced by estradiol. Results supported the hypotheses that F1 near the beginning of deviation produces inhibin and estradiol a




Biochim Biophys Acta. 2003 Oct 1;1629(1-3):92-101.
Nrf2, not the estrogen receptor, mediates catechol estrogen-induced activation of the antioxidant responsive element.

Lee JM, Anderson PC, Padgitt JK, Hanson JM, Waters CM, Johnson JA.

School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, WI 53705, USA.

The antioxidant responsive element (ARE) plays an important role in the gene expression of phase II detoxification enzymes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1), and NF-E2-related factor2 (Nrf2) is the transcription factor for the ARE-driven genes. Interestingly, estrogen receptor (ER) was reported to increase NQO1 gene expression through the ARE. In this study, we investigated the role of ER and Nrf2 in ARE activation using IMR-32 cells and mouse primary astrocytes. Among tested estrogen-related compounds, only catechol estrogens (i.e. 4-hydroxyestradiol) activated the ARE. Since 4-hydroxyestradiol-induced ARE activation was not inhibited by either 17beta-estradiol or tamoxifen, and overexpression of ER-alpha decreased 4-hydroxyestradiol-induced ARE activation, ARE activation by catechol estrogen was independent of ER. Nrf2, however, was very important in the 4-hydroxyestradiol-induced ARE activation. 4-Hydroxyestradiol did not activate the ARE in Nrf2 knockout (-/-) primary astrocytes, but did activate the ARE when Nrf2 was transfected into Nrf2-/- astrocytes. In addition, dominant negative Nrf2 completely blocked 4-hydroxyestradiol-induced ARE activation in Nrf2+/+ astrocytes, and only 4-hydroxyestradiol induced Nrf2 nuclear translocation in IMR-32 cells. A selective phosphatidylinositol 3-kinase (PI3-kinase) inhibitor (LY294002) blocked 4-hydroxyestradiol-induced Nrf2 nuclear translocation and NQO1 activity induction in IMR-32 cells. Taken together, these observations suggest that 4-hydroxyestradiol activates the ARE by a PI3-kinase-Nrf2 dependent mechanism, not involving ER.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14522084&dopt=Abstract estradiol




Neuro Endocrinol Lett. 2003 Jun-Aug;24(3-4):130-6.
17-beta estradiol down regulates ganglionic microglial cells via nitric oxide release: presence of an estrogen receptor beta transcript.

Stefano GB, Zhu W, Mantione K, Jones D, Salamon E, Cho JJ, Cadet P.

Neuroscience Research Institute, State University of New York College at Old Westbury, Old Westbury, New York 11568, USA. gstefanunynri.org

OBJECTIVES: In earlier studies we have demonstrated that 17-beta-estradiol and an estrogen cell surface receptor can be found on various human cells where they are coupled to nitric oxide release. We also demonstrated the presence of estrogen signaling in Mytilus edulis ganglia. In the present report, we sought to determine a function for these ganglionic estrogen receptors, transcending a reproductive role for estrogen. MATERIAL & METHODS: Ganglionic microglial egress from excised pedal ganglia was examined microscopically following pharmacological treatments designed to determine a role for 17-beta-estradiol in microglial regulation via nitric oxide. Additionally, we examined the tissue by RT-PCR and sequence analysis for the estrogen receptor beta gene. RESULTS: In ganglia incubated with varying concentrations of 17-beta-estradiol-BSA there is a significant drop in microglial egress at the 24 hour observation period (58.7 +/- 7.4 vs. 17-beta-estradiol-BSA exposed = 14.7 +/- 1.5; P<0.01), which can be antagonized by tamoxifen and significantly diminished by L-NAME, a nitric oxide synthase inhibitor. By RT-PCR and sequence analysis Mytilus edulis pedal ganglia was found to express a 266 bp fragment of the estrogen receptor-beta gene, which exhibits 100% sequence identity with the human counterpart. CONCLUSION: These data suggest that 17-beta-estradiol-BSA is working on estrogen cell surface receptors since 17-beta-estradiol-BSA does not enter the cytoplasm and that these receptors are coupled to constitutive nitric oxide release. This study demonstrates that 17-beta-estradiol can down regulate microgli




Neuro Endocrinol Lett. 2003 Jun-Aug;24(3-4):137-40.
The presence of 17-beta estradiol in Mytilus edulis gonadal tissues: evidence for estradiol isoforms.

Zhu W, Mantione K, Jones D, Salamon E, Cho JJ, Cadet P, Stefano GB.

Neuroscience Institute, State University of New York College at Old Westbury, Old Westbury, New York 11568, USA.

OBJECTIVES: In earlier studies, we demonstrate that 17-beta -estradiol and an estrogen cell surface receptor can be found on various human cells, i.e., vascular endothelial, monocytes, and granulocytes, where they are coupled to nitric oxide release. We further demonstrated this phenomenon in the marine mussel Mytilus edulis ganglionic tissues. In the present report we sought to determine if estrogen can be found in M. edulis reproductive tissues. MATERIAL & METHODS: We determined the presence of 17-beta -estradiol via high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA) in the animals gonads. This substance was further identified via nanoelectro-spray ionization quadrupole time of flight mass spectrometry (Q-TOF-MS). RESULTS: 17-beta -estradiol was identified and quantified in Mytilus gonads. Interestingly, we also determined that estradiol isoforms also were present in this tissue. CONCLUSION: These data demonstrate that 17-beta-estradiol and an estradiol isoform is present in M. edulis gonadal tissues, suggesting that they have functions related to reproduction. This further suggests that estrogen's association with reproductive activities has a long evolutionary history and that this association began in invertebrates.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14523346&dopt=Abstract estradiol