Hypertension. 2002 Apr;39(4):854-9.
Catecholamines block 2-hydroxyestradiol-induced antimitogenesis in mesangial cells.

Zacharia LC, Jackson EK, Gillespie DG, Dubey RK.

Center for Clinical Pharmacology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pa, USA.

Methylation of 2-hydroxyestradiol to 2-methoxyestradiol by catechol-O-methyl transferase (COMT) mediates the antimitogenic effects of 2-hydroxyestradiol on vascular smooth muscle cells. Moreover, 2-hydroxyestradiol inhibits growth of glomerular mesangial cells (GMCs). Because catecholamines are substrates for COMT, which is expressed in GMCs, we hypothesize that catecholamines may abrogate the antimitogenic effects of 2-hydroxyestradiol on GMCs by competing for COMT and inhibiting 2-methoxyestradiol formation. To test this hypothesis, we investigated the antimitogenic effects of 2-hydroxyestradiol on rat GMCs in the presence and absence of catecholamines. The capability of GMCs to methylate 2-hydroxyestradiol in the presence and absence of catecholamines was also evaluated. GMCs metabolized 2-hydoxyestradiol in a concentration-dependent manner with a V(max) of 12.03+/-0.32 pmol/10(6) cells/min and an apparent K(m) of 0.23+/-0.04 micromol/L. Norepinephrine (10 micromol/L) and epinephrine (10 micromol/L) significantly inhibited methylation of 0.25 micromol/L 2-hydroxyestradiol. Norepinephrine concentration-dependently abrogated the ability of 2-hydroxyestradiol to inhibit 3H-thymidine incorporation (index of DNA synthesis). In the presence of 5, 10, and 40 micromol/L norepinephrine, the inhibitory effect of 0.1 micromol/L 2-hydroxyestradiol on 3H-thymidine incorporation was reduced from 51+/-0.7% to 46+/-0.4%, 39+/-0.3%, and 25+/-0.7%, respectively. Similar to DNA synthesis, the inhibitory effects of 2-hydroxyestradiol on cell number and 3H-proline incorporation (index of collagen synthesis) on GMCs were abrogated by catecholamines. Our findings provide evidence that methylation of 2-hydroxyestradiol inhi




Hypertension. 2002 Apr;39(4):874-9.
Methoxyestradiols mediate estradiol-induced antimitogenesis in human aortic SMCs.

Barchiesi F, Jackson EK, Gillespie DG, Zacharia LC, Fingerle J, Dubey RK.

Department of Obstetrics and Gynecology, Clinic for Endocrinology, University Hospital Zurich, Zurich, Switzerland.

Estrogen receptors (ERs) are considered to mediate the ability of 17beta-estradiol (estradiol) to reduce injury-induced proliferation of vascular smooth muscle cells (VSMCs), leading to vascular lesions. However, the finding that estradiol attenuates formation of vascular lesions in response to vascular injury in knockout mice that lack either ER-alpha or ER-beta challenges this concept. Our hypothesis is that the local metabolism of estradiol to methoxyestradiols, metabolites of estradiol with little affinity for ERs, mediates the ER-independent antimitogenic effects of estradiol on VSMCs. In human VSMCs, 2-methoxyestradiol and 2-hydroxyestradiol were more potent than was estradiol in inhibiting DNA synthesis (3[H]-thymidine incorporation), collagen synthesis (3[H]-proline incorporation), cell proliferation (cell number), and cell migration (movement of cells across a polycarbonate membrane). The inhibitory effects of estradiol on VSMCs were enhanced by cytochrome-P450 (CYP450) inducers 3-methylcholanthrene and phenobarbital. Moreover, the inhibitory effects of estradiol were blocked in the presence of the CYP450 inhibitor 1-aminobenzotriazole and the catechol-O-methyltransferase inhibitors quercetin and OR486. Both OR486 and quercetin blocked the conversion of 2-hydroxyestradiol to 2-methoxyestradiol; moreover, they blocked the antimitogenic effects of 2-hydroxyestradiol but not of 2-methoxyestradiol. The ER antagonist ICI182780 blocked the inhibitor effects of estradiol on VSMCs, but only at concentrations (>50 micromol/L) that also inhibit the metabolism of estradiol to hydroxyestradiols (precursors of methoxyestradiols). In conclusion, the inhibitory effects of locally applied




Psychopharmacology (Berl). 2002 Apr;161(1):107-12. Epub 2002 Feb 21.
Trough oestradiol levels associated with cognitive impairment in post-menopausal women after 10 years of oestradiol implants.

File SE, Heard JE, Rymer J.

Psychopharmacology Research Unit, Centre for Neuroscience, Hodgkin Building, King's College London, Guy's Campus, London SE1 1UL, UK. sandra.filcl.ac.uk

RATIONALE: Oestrogen treatment has been found to improve memory in healthy post-menopausal women, but the effects are small, especially when socio-economic status is controlled. There is some evidence that with long-term treatment the benefits decline, or reverse. OBJECTIVE: To examine the effects of 10 years of oestradiol implants on attention, memory and frontal lobe function in healthy women (aged 51-72 years) who had undergone a surgical menopause. METHODS: In an open study, patients were recruited from the Guy's Hospital menopause clinic and were tested just before receiving a new implant. Exclusion criteria included any form of psychoactive medication, IQ<90, English not the first language and anxiety or depression scores in the clinical range. All patients had been receiving HRT with an oestradiol implant for about 10 years. Each patient was pair-matched to a woman who had never received HRT. Eighteen pairs were matched for age, IQ, socio-economic status, years of secondary education, and occupation. They completed questionnaires, mood rating scales and a battery of cognitive tests. RESULTS: The patients with oestradiol implants had significantly greater psychological and somatic menopausal symptoms and significantly worse mental flexibility (rule reversal) and long-term episodic memory than did the control group who had never received HRT. Analysis of covariance showed that the difference in menopausal symptoms did not account for the cognitive differences. There were no differences in a test of sustained attention or in a category generation task or in self-ratings of mood after the stress of cognitive testing. CONCLUSIONS: Long-term t




Horm Behav. 2002 May;41(3):259-66.
Endogenous estradiol and testosterone levels are associated with cognitive performance in older women and men.

Wolf OT, Kirschbaum C.

Institute of Experimental Psychology II, University of Duesseldorf, Germany. oliver.wolni-duesseldorf.de

Relatively few studies have investigated the relationship between endogenous sex steroid levels and cognition in older people and the reported results have been inconsistent. A number of experimental hormone replacement studies have suggested that estrogen replacement in older women enhances cognition, especially verbal memory. In contrast, little research has been done focusing on men. In the current study the association between endogenous sex steroids (estradiol and testosterone) and cognition was investigated in 38 healthy older women (mean age 68 years) and 30 healthy older men (mean age 69 years). Five cognitive tests measuring verbal memory, spatial memory, verbal fluency, mental rotation, and susceptibility to interference were administered. Results revealed that in women higher estradiol levels as well as testosterone levels were associated with better verbal memory (paired associates and estradiol; r =.38, P < 0.05; paired associates and testosterone; r =.33, P < 0.05;). Moreover estradiol, but not testosterone was associated with less susceptibility to interference (Stroop color word test; r = -0.34, P < 0.05). In men the only significant association was a negative correlation between testosterone and verbal fluency (r = -0.38, P < 0.05). The associations observed in this small study support the notion that estradiol is protecting verbal memory and possibly also frontal lobe mediated functions in older women. In contrast to the positive findings in women endogenous sex steroids do not appear to be closely linked to better cognition in older men. (c) 2002 Elsevier Science (USA).

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11971659&dopt=Abstract estradiol




Horm Behav. 2002 May;41(3):297-305.
Exposure to estradiol before but not during acquisition of LiCl-induced conditioned taste avoidance accelerates extinction.

Chambers KC, Hayes UL.

Department of Psychology, University of Southern California, Los Angeles 90089, USA. kchambecf.usc.edu

Estradiol accelerates extinction of LiCl-induced conditioned taste avoidance when it is present continuously before and during acquisition. We have suggested that the effect of estradiol on extinction is due to its illness-associated, rather than learning-associated, properties. If this were the case, then one would expect estradiol to act before but not during acquisition. This expectation is based on previous work showing attenuation of learned taste avoidance when rats are given distal preexposure (greater than 24 h before conditioning) or proximal preexposure (less than 24 h before conditioning) to the illness-inducing agent LiCl before acquisition of a LiCl-induced conditioned taste avoidance. In three separate experiments, estradiol was administered during three different time periods via subcutaneous implantation of a 10-mm estradiol-filled capsule. In each experiment, the extinction of estradiol-treated females was compared to that of females implanted with empty capsules. In the first experiment, female rats were given distal exposure to estradiol before acquisition. Capsules were implanted 11 days before acquisition and were removed 2 days before acquisition. In the second experiment, female rats were given proximal exposure to estradiol before acquisition. Capsules were implanted 2.5 h before LiCl was paired with a sucrose solution and were removed 16.5 h later. In the third experiment, female rats were given exposure to estradiol during acquisition. Capsules were implanted at the same time as LiCl administration and were removed 18 h later. The only estradiol-treated females to show accelerated extinction were those given distal preexposure to estradiol in Experiment 1. These data do not sup




Horm Behav. 2002 May;41(3):316-20.
Food deprivation inhibits estrous behavior in hormone-treated Syrian hamsters despite elevated estradiol levels.

Jones JE, Pick RR, Wade GN.

Center for Neuroendocrine Studies, University of Massachusetts, Amherst 01003-7720, USA. jonens.umass.edu

Estradiol and progesterone (P) induce female mammalian reproductive behaviors, which are, in turn, sensitive to food availability. When ovariectomized, steroid-primed hamsters are food deprived for 48 h, estrous behavior is suppressed. While this suppression of estrous behavior may be due to alterations in neural steroid receptor levels, it is also possible that decreased levels of circulating estradiol could be involved in mediating this suppression. Ovariectomized Syrian hamsters given varying doses of estradiol benzoate (EB) and P were tested to determine whether increasing doses of sex steroids would overcome the suppressive effects of food deprivation on estrous behavior. As expected, lordosis duration decreased in food-deprived animals. Increasing the levels of EB, but not P, increased lordosis duration in the food-deprived animals so that animals who were given 20 microg of EB had lordosis durations significantly longer than food-deprived hamsters that received 1.5 microg and 2.5 microg EB. Following an injection of 2.5 microg of EB, food-deprived hamsters actually had higher circulating levels of estradiol than ad libitum-fed animals. Therefore, increasing circulating levels of estradiol can increase lordosis durations in fasted animals; however, the suppression of estrous behavior occurs despite increased circulating estradiol levels in ovariectomized, steroid-treated animals. The most parsimonious explanation for this phenomenon is a deprivation-induced reduction in neural responsiveness to estradiol. (c) 2002 Elsevier Science (USA).

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11971665&dopt=Abstract estradiol




Obstet Gynecol. 2002 May;99(5 Pt 1):726-30.
The association between serum estradiol level and hearing sensitivity in postmenopausal women.

Kim SH, Kang BM, Chae HD, Kim CH.

Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, South Korea.

OBJECTIVE:To estimate whether hearing sensitivity in postmenopausal women is associated with serum estradiol level or bone mineral density.METHODS:Serum estradiol level, bone mineral densities of the lumbar vertebrae and femoral neck, and hearing sensitivity were measured in 1830 postmenopausal women. Serum estradiol level was measured by radioimmunoassay, and dual energy x-ray absorptiometry was used to measure bone mineral densities of the lumbar vertebrae and femoral neck. Hearing sensitivity was evaluated by pure tone audiometry. Age, serum estradiol level, bone mineral densities of the lumbar vertebrae and femoral neck, and the proportion of women on hormone replacement therapy were analyzed in women with and without hearing loss.RESULTS:On univariate analysis, significant differences were found in mean age, serum estradiol level, bone mineral densities of the lumbar vertebrae and femoral neck, and the proportion of women on hormone replacement therapy between the two groups (mean +/- standard deviation, 59.4 +/- 5.6 versus 56.9 +/- 4.7 years, P <.001; 8.4 +/- 3.8 versus. 9.9 +/- 8.7 pg/mL, P <.001; 0.85 +/- 0.14 versus 0.88 +/- 0.15 g/cm(2), P <.01; 0.65 +/- 0.10 versus 0.68 +/- 0.10 g/cm(2), P <.005; 0.006% versus 0.03%, P <.05, respectively). On multiple logistic regression analysis, significant association was found between age and hearing loss and between serum estradiol level and hearing loss (P <.001, P =.02, respectively).CONCLUSION:This study suggests that a lower level of serum estradiol possibly impedes hearing sensitivity in postmenopausal women.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11978279&dopt=Abstract estradiol




Life Sci. 2002 Feb 22;70(14):1621-30.
Effect of treatment with different doses of 17-beta-estradiol on the insulin receptor.

Gonzalez C, Alonso A, Grueso NA, Esteban MM, Fernandez S, Patterson AM.

Department of Functional Biology, Physiology Area, University of Oviedo, Spain. tinoorreo.uniovi.es

The mechanism for the development of insulin resistance in normal pregnancy is complex and is associated with serum levels of sex hormones. However, the influence of these hormones on the early steps of insulin action has not been extensively studied, although the potentially beneficial effect of estradiol on glucose homeostasis has been reported. In this paper, we attempted to determine the effect of 17-beta-estradiol on the insulin receptor of ovariectomized rats treated with different doses of hormones. Our results showed a tissue-dependent response to estradiol. We found that low doses of estradiol increased the amount of insulin receptors in liver and muscle on days 6 and 11 of treatment but not in adipose tissue, and after 16 days only the muscle responsed in this way. On the other hand, high doses of estradiol significantly decreased the amount of insulin receptors, at least in muscle and adipose tissue. We believe that the low concentrations of 17-beta-estradiol (similar to early pregnancy) could be responsible for the increase in insulin sensitivity by increasing the amount of insulin receptors in peripheral tissues. When the hormone levels were high (similar to late pregnancy) the amount of insulin receptors decreased in peripheral tissues, and insulin sensitivity is diminished just as in late pregnancy. The specific molecular mechanism for this action is as yet unknown.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11991250&dopt=Abstract estradiol




Theriogenology. 2002 Jan 15;57(2):811-21.
Involvement of steroid hormones on in vitro maturation of pig oocytes.

Dode MA, Graves C.

National Center for Research on Beef Cattle, EMBRAPA, Campo Grande, MS, Brazil. margoenargen.embrapa.br

The purpose of this study was to determine if the addition of steroid hormones into the culture medium could influence the in vitro maturation of pig oocytes. The cumulus-oocyte complexes (COCs). collected from follicles of 2-5 mm diameter, were matured in steroid-free medium supplemented with various concentrations of estradiol-17beta (0-3000 ng/ml), progesterone (0-5000 ng/ml) and testosterone (0-300 ng/ml). The COCs were cultured for 42 h, then fertilized in vitro. We analyzed nuclear and cytoplasmic maturation with lacmoid stain 20 h after in vitro insemination. We observed no significant effect (P > 0.05) on the percentage of oocytes completing nuclear or cytoplasmic maturation or the number of sperm penetrating each oocyte for any concentration of progesterone, estradiol-17beta or testosterone. Similarly, adding a combination of those hormones to the medium did not significantly (P > 0.05) affect any of the criteria. In order to determine if there was a possible secretion of steroids during maturation, we added COCs, denuded oocytes and stripped cumulus cells to drops of a steroid-free medium and cultured them for 42 h, after which we analyzed the medium, before and after culture, for the presence of progesterone, estradiol-17beta and testosterone by radioimmunoassay (RIA) analysis. COCs, as well as cumulus cells alone, secreted similar amounts of estradiol (43.3 and 37.5 pg/ml, respectively) and progesterone (4.24 and 4.79 ng/ml, respectively) into the maturation medium. A small amount of estradiol (28.8 pg/ml) was also detected when oocytes were cultured alone. These results indicate that no steroids need to be added to the maturation medium of pig oocytes and that the COCs secrete steroids during maturation. It is possible that the amounts pro