Mol Pharmacol. 2002 Jan;61(1):127-35.
Potentiation of human alpha4beta2 neuronal nicotinic acetylcholine receptor by estradiol.
Curtis L, Buisson B, Bertrand S, Bertrand D.
Department of Physiology, Faculty of Medicine, Geneve, Switzerland.
The modulation of neurotransmitter receptors by various substances can reflect important physiological mechanisms involved in the regulation of neural function. Furthermore, such substances, in particular specific allosteric modulators, can reveal promising therapeutic targets for diseases of the nervous system. From this perspective, we investigated the effects of the steroid hormone estradiol on human neuronal nicotinic acetylcholine receptors expressed either in Xenopus laevis oocytes or human embryonic kidney cells. Acetylcholine-evoked currents were potentiated both by pre- and coapplications of estradiol in alpha4beta2 and alpha4beta4 receptors, but not in alpha3beta2 or alpha3beta4 receptors. The reversible potentiation of alpha4-containing receptors could be induced within seconds in X. laevis oocytes and at micromolar concentrations of estradiol. The potentiation was greatest for responses evoked by low concentrations of acetylcholine, resulting in an apparent increase of receptor affinity. At the single channel level, estradiol potentiation resulted from an increase in opening probability. Finally, the use of functional chimeric or truncated alpha4 subunits demonstrated that a site at the C-terminal tail of the alpha4 subunit is required for estradiol potentiation. These results suggest the presence of a specific site at the human nicotinic acetylcholine receptor alpha4 subunit through which estradiol can cause an allosteric potentiation of acetylcholine-evoked responses.
Early Pregnancy. 2001 Jul;5(3):176-90.
Correlation between serum levels of 17 beta-estradiol, progesterone and beta-human chorionic gonadotropin and the karyotype of first trimester anembryonic and embryonic pregnancies.
Agudelo B, Muneton CM, Vasquez G, Ramirez JL.
Departament of Obstetrics and Gynecology, University of Antioquia, Medellin, Colombia.
We aimed at establishing the correlation between karyotype of anembryonic and embryonic first trimester pregnancies and serum levels of beta-hCG, 17beta-estradiol and progesterone. Chromosomal analyses were performed on products of conceptions lower than 12 weeks, using standard-banding protocols. Measurements of 17beta-estradiol and progesterone were carried out by immunoenzymatic assays and beta-hCG by radioimmunoanalysis (RIA). Chromosomal analyses among 11 spontaneous abortions revealed 6 (54,5%) to be normal and 5 (45,5%) abnormal; of these latter, 4 were anembryonic pregnancies (44,4% total frequency). Serum beta hCG and beta-estradiol average levels were lower in the anembryonic pregnancies but did not reveal significant differences with normal levels. Hormonal levels were correlated with karyotype results and it was found that average beta-hCG value was 3.8 times higher in cases with abnormal karyotype than in those in whom it was normal (p <0.05). Linear correlation analyses between hormonal measurements in anembryonic pregnancies were statistically significant (p <0.05). Correlations between beta-hCG and progesterone, beta-hCG and 17-beta estradiol, and the latter with progesterone, proved to be significant in the group with abnormal karyotype (p < 0.05). Anembryonic pregnancies present high frequency of chromosomal anomalies; such pregnancies with abnormal karyotype have a high serum level of beta-hCG; this condition increased the rate of abortion.
Horm Metab Res. 2001 Dec;33(12):733-8.
Rapid effects of calciotropic hormones on female rat enterocytes: combined actions of 1,25(OH)2-vitamin D3, PTH and 17beta-estradiol on intracellular Ca2+ regulation.
Departamento de Biologia, Bioquimica y Farmacia, Universidad Nacional del Sur, San Juan 670, 8000 Bahia Blanca, Argentina. gpicottriba.edu.ar
1,25(OH)(2)-Vitamin D(3) [1,25(OH)(2)D(3)], PTH and 17beta-estradiol increase intracellular Ca(2+) levels ([Ca(2+)](i)) in rat enterocytes by stimulating inner Ca(2+) store mobilization and voltage-dependent Ca(2+) channels through non-genomic activation of second-messenger cascades. The participation of store-operated Ca(2+) (SOC) channels in 17beta-estradiol regulation of enterocyte [Ca(2+)](i) has also been suggested. The aim of this work was to investigate whether PTH and/or 17beta-estradiol exert additive or synergistic effects acting in concert with the classic intestinal calciotropic hormone 1,25(OH)(2)D(3). Fura-2-loaded rat duodenal cells were stimulated using rPTH (10 nM), 17beta-estradiol (0.1 nM) or 1,25(OH)(2)D(3) (0.1 nM). The resulting Ca(2+) signal was characterized by an almost immediate rise in [Ca(2+)](i) (within 30 s) rapidly reaching peak levels, followed by a plateau phase that remained sustained as long as the cells were exposed to the stimulus. The addition of PTH at the sustained phase induced by 1,25(OH)(2)D(3) or, conversely, the addition of the secosteroid after the PTH-induced effect, did not induce additional increases in [Ca(2+)](i). Simultaneous treatment with both hormones resulted in an elevation of [Ca(2+)](i) equivalent to the maximal level caused by either agonist alone, suggesting common components for [Ca(2+)]i stimulation by PTH and 1,25(OH)(2)D(3). Treatment with 17beta-estradiol at the sustained phase induced by 1,25(OH)(2)D(3) or, conversely, treatment with the secosteroid after the 17beta-estradiol effect, induced additional increments in [Ca(2+)](i) (58 % and 63 %, respectively). Simultaneo
Horm Metab Res. 2001 Dec;33(12):744-7.
The effects of postmenopausal hormone replacement therapy and oral contraceptives on the endogenous estradiol metabolism.
Mueck AO, Seeger H, Graser T, Oettel M, Lippert TH.
Section of Endocrinology and Menopause, Department of Obstetrics and Gynecology, University of Tubingen, Schleichstrasse 4, 72076 Tubingen, Germany.
The estradiol metabolism may be of clinical relevance in the pathophysiology of various diseases; the increase in D-ring metabolites over A-ring metabolites in breast cancer patients is of special interest. Since estrogen therapy has been blamed for increasing the risk of breast cancer, the effects of hormonal replacement therapy (HRT) and oral contraception were investigated on the ratio of the main D-ring metabolite, 16alpha-hydroxyestrone (16-OHE1), to the main A-ring metabolite, 2-hydroxyestrone (2-OHE1). In our study, hormone replacement therapy (HRT) in postmenopausal women consisted of administration of estradiol valerate either with or without addition of the progestin dienogest. In the second part of the study, women of reproductive age received ethinylestradiol plus dienogest or ethinylestradiol plus norethisterone acetate as oral contraceptives (OC). 2-OHE1 and 16-OHE1 were measured by enzyme immunoassay in 8 h night-urine collected before and after 3 months of hormone administration. With HRT, that is, estradiol valerate or estradiol valerate plus dienogest, the ratios before treatment were 0.47 and 0.60; after 3 months, they were 0.54 and 0.52, respectively. There were no significant differences. With oral contraception, that is, ethinylestradiol plus dienogest or norethisterone acetate, the ratios before administration were 0.62 and 0.68, vs. 0.31 and 0.54 after 3 months, respectively. The ratio after ethinylestradiol and dienogest was significantly lower after treatment. HRT and OC in the estrogen-progestin combinations tested did not impose any negative effects on estradiol metabolism--they did not elicit a higher D-ri
J Exp Zool. 2002 Jan 1;292(1):52-72.
Vitellogenin from female and estradiol-stimulated male river lampreys (Lampetra fluviatilis L.).
Mewes KR, Latz M, Golla H, Fischer A.
Abteilung Experimentelle Morphologie, Institut fur Zoologie, Universitat Mainz, D-55099 Mainz, Germany. afischeail.uni-mainz.de
The influence of estradiol-17beta (E(2)) on vitellogenesis is well documented for a number of oviparous craniates. We have examined the role that estradiol-17beta plays in the induction and regulation of vitellogenin synthesis in the maturing European river lamprey, Lampetra fluviatilis. In both females and males the estradiol-17beta concentrations in the plasma reached comparable maximum values in March, only a few weeks before spawning. Throughout the spawning run, the vitellogenin titer in the blood of females remains rather constant while the ovary volume increases. In contrast, we never found circulating VTG in untreated male lampreys. The synthesis and secretion of the yolk precursor molecule can be induced in males, however, by high doses of estradiol injected into the coelom. Lamprey vitellogenin was isolated from the blood of maturing females as well as from hormone-stimulated males and identified by its immunological and electrophoretic properties. In the blood plasma of both maturing female and estradiol-treated male lampreys it always appears simultaneously in two different molecular forms: a vitellogenin monomer with an apparent molecular weight of 310-330kDa and a dimer. After SDS treatment, vitellogenin is represented as a 212-kDa polypeptide. Copyright 2002 Wiley-Liss, Inc.
Hum Reprod. 2002 Jan;17(1):221-7.
Determinants of early follicular phase gonadotrophin and estradiol concentrations in women of late reproductive age.
Cramer DW, Barbieri RL, Fraer AR, Harlow BL.
Obstetrics and Gynecology Epidemiology Center, Boston, MA 02115, USA. dcrameartners.org
BACKGROUND: FSH and estradiol measured during the menstrual (basal) phase of cycles predict the success of infertility treatment; but the role of these hormones as markers for ovarian reserve in normal populations needs further study. METHODS AND RESULTS: From a cohort study of depressed and non-depressed women, a subset of 406 non-depressed women between the ages of 36 and 45 years with spontaneous periods were selected and their concentrations and determinants of basal hormones measured at study entry, 6 and 12 months later were described. FSH and LH increased significantly over the 12 months of observation (P <or= 0.001), but considerable variation was noted in FSH and estradiol in some women monitored over the three cycles. Concentrations often varied between a pattern of low FSH, high estradiol in one cycle and high FSH, low estradiol in another. In multivariate models focusing on the maximum observed hormone concentration, significant predictors included: increasing age (P < 0.0001), smoking (P = 0.04), and shorter cycle length (P < 0.0001) during adolescence (P < 0.0001) associated with higher FSH; increasing age (P < 0.0266) and lower body mass index (P < 0.0289) associated with higher LH; and a greater number of estimated ovulatory cycles associated with higher estradiol (P < 0.0425). CONCLUSIONS: Early reproductive landmarks, smoking, body weight, and factors that determine number of ovulatory cycles impact on ovarian/pituitary physiology in late reproductive life.
Mol Hum Reprod. 2002 Jan;8(1):68-74.
Differential regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase by progesterone withdrawal in human endometrial stromal cells.
Sugino N, Karube-Harada A, Kashida S, Takiguchi S, Kato H.
Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan. obgyo.cc.yamaguchi-u.ac.jp
The present study was undertaken to investigate the role of estrogen and progesterone in the expression of copper-zinc superoxide dismutase (Cu,Zn-SOD) and manganese SOD (Mn-SOD) in human endometrial stromal cells (ESC). ESC were incubated with estradiol (10(-8) mol/l), medroxyprogesterone acetate (MPA, 10(-6) mol/l), or estradiol + MPA for 18 days. MPA significantly increased Cu,Zn-SOD and Mn-SOD mRNA levels and enzyme activities as well as the mRNA level of insulin-like growth factor-binding protein-1 (IGFBP-1), a marker for decidualization. Estradiol only augmented the effects of MPA on Cu,Zn-SOD activity and IGFBP-1 mRNA level, and estradiol alone had no effect. To study the withdrawal of estrogen and progesterone (EP withdrawal), ESC that had been treated with estradiol + MPA for 12 days were washed and then incubated with or without estradiol + MPA for a further 11 days. Cu,Zn-SOD mRNA levels and activities declined after EP withdrawal, while they were gradually increased by the continuous treatment with estradiol + MPA. In contrast, Mn-SOD mRNA levels and activities were not affected by EP withdrawal. IGFBP-1 mRNA levels were significantly increased 4 days after EP withdrawal and decreased thereafter, whereas they were gradually increased by the continuous treatment with estradiol + MPA. In conclusion, Cu,Zn-SOD, Mn-SOD and IGFBP-1 are differently regulated by estrogen and progesterone in human ESC. The decrease in Cu,Zn-SOD after the ovarian steroid withdrawal may be involved in endometrial breakdown.
J Med Assoc Thai. 2001 Jul;84(7):1015-20.
Effect and safety of 17 beta-estradiol vaginal tablet in postmenopausal women with urogenital symptoms.
Manonai J, Theppisai U, Chittacharoen A.
Department of Obstetrics and Gynaecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
OBJECTIVE: To evaluate the effects of a 17 beta-estradiol vaginal tablet on urogenital symptoms, vaginal pH, vaginal cytology, endometrial thickness, and plasma estradiol level in postmenopausal women with urogenital symptoms. METHOD: Twenty-seven postmenopausal women with urogenital symptoms received 25 microg of a 17 beta-estradiol tablet intravaginally daily for the first 2 weeks, followed by 10 weeks of twice a week dosage. The results of urogenital symptoms, vaginal pH, vaginal cytology, endometrial thickness, and plasma estradiol level were analysed. RESULTS: The urogenital symptoms improved significantly in all women. The mean vaginal pH was significantly decreased. The vaginal cytology showed estrogenic effect on the karyopyknotic index and the maturation value. There was no significant difference in endometrial thickness and level of plasma estradiol before and after treatment. There was one case of vaginal bleeding from endometrial proliferation. CONCLUSION: Local vaginal treatment of 17 beta-estradiol (25 microg) had a positive effect on the urogenital symptoms, vaginal pH, and vaginal cytology. No elevation of plasma estradiol level was detected after treatment.
Endocrine. 2001 Aug;15(3):271-6.
Herbimycin, a tyrosine kinase inhibitor with Src selectivity, reduces progesterone and estradiol secretion by human granulosa cells.
Rice VM, Chaudhery AR, Oluola O, Limback SD, Roby KF, Terranova PF.
Center for Reproductive Sciences, Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, USA.
The purpose of the present study was to investigate whether the tyrosine kinase inhibitor herbimycin with some selectivity to block Src would alter the stimulatory effects of follicle-stimulating hormone (FSH) and cyclic adenosine monophosphate (cAMP) on estradiol secretion by human granulosa cells. Granulosa cells were taken from ovaries of premenopausal women undergoing oophorectomy for reasons unrelated to ovarian pathology. Granulosa cells from follicles ranging from 5-20 mm in diameter were subjected to culture. Granulosa cells were cultured with human FSH (2 ng/mL) or cAMP (0-1 mM) and testosterone (1 microM) in the presence and absence of herbimycin (0-2 pM). Media were collected at 24, 48, and 72 h. Accumulation of cAMP, progesterone, and estradiol in the media was determined by radioimmunoassay. Herbimycin dose dependently inhibited the ability of FSH to induce increases in progesterone and estradiol secretion. Although herbimycin increased (p < 0.0001) the accumulation of cAMP in response to FSH, this was evident only at the high concentrations of herbimycin (2 microM). To determine whether herbimycin would inhibit the ability of exogenous cAMP to induce estradiol and progesterone secretion, granulosa cells were incubated with 0-1 mM cAMP in the presence and absence of various doses of herbimycin. Herbimycin inhibited cAMP-induced estradiol and progesterone secretion in granulosa cells. The results from seven experiments indicate that herbimycin inhibits FSH stimulation of estradiol and progesterone secretion and that this inhibition may be, in part, at post-cAMP site(s).
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