J Endocrinol. 2003 Jun;177(3):453-60.
Prolactin release during the estradiol-induced LH surge in ewes: modulation by progesterone but no evidence for prolactin-releasing peptide involvement.

Skinner DC, Caraty A.

Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA. DCuwyo.edu

An estradiol-induced prolactin surge accompanies the LH surge in several species, including sheep. However, the neural mechanisms underlying this surge remain poorly understood. A first study on estradiol- and progesterone-treated ovariectomized ewes examined whether the prolactin surge, like the LH surge, is sensitive to progesterone. Our data clearly showed that the estradiol-induced prolactin surge in the ewe is blocked by continuous exposure to progesterone and, importantly, that this blockade is overcome by pretreatment with the progesterone receptor antagonist, RU486. In a second study, we established that the generation of the prolactin surge is not dependent on the co-secretion of a prolactin-releasing peptide in the hypophyseal portal blood or cerebrospinal fluid. The neuronal pathways targeted by estradiol and progesterone to modulate prolactin secretion at the time of the LH surge remain to be identified. Importantly, it has not been established whether there is any overlap in the neuronal systems generating the gonadotropin-releasing hormone and prolactin surges.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12773126&dopt=Abstract estradiol




Biol Reprod. 2003 Oct;69(4):1201-7. Epub 2003 May 28.
Does alligator testis produce estradiol? A comparison of ovarian and testicular aromatase.

Lance VA, Conley AJ, Mapes S, Steven C, Place AR.

Center for Reproduction of Endangered Species, San Diego, California 92112, USA. lvalentunstroke.sdsu.edu

Testicular secretion of estradiol is necessary for normal spermatogenesis and male reproductive physiology in humans and rodents. The role of estradiol in nonmammalian vertebrates remains unknown, but elevated circulating estradiol has been reported in male lizards, alligators, and various bird species. We have been unable to detect circulating estradiol in male alligators; therefore, we reexamined the question of testicular production of estradiol in alligators using more rigorous assay procedures. A large pool of plasma from a male alligator was extracted and run through an HPLC column. Immunoreactive estradiol-like material eluted coincident with authentic estradiol. By using an ultrasensitive RIA and processing large volumes of male plasma (1000 microl), we were able to measure estradiol. Estradiol in male alligators ranged from 0.23 to 3.14 pg/ml, whereas estradiol in immature female alligators ranged from 14 to 66 pg/ml. Aromatase activity in microsomes from adult alligator ovarian tissue was 36.2 +/- 1.6 pmol mg-1 h-1, whereas activity in testicular microsomes ranged between 0.92 and 2.38 pmol mg-1 h-1. Ovarian aromatase activity was inhibited in a concentration-dependent fashion by Fadrozole, but the essentially background activity of testicular aromatase was not inhibited at any concentration of Fadrozole. Likewise, a comparison of alligator testicular and ovarian aromatase mRNA expression gave a similar result: the ovarian expression was 600-fold higher and brain tissue was 10-fold higher than that of the testis. Circulating estradiol in male alligators is probably of extragonadal origin, and the testis produces little if any of this steroid.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12773408&dopt=Abstract estradiol [PubMed - indexed for MEDLINE]



Environ Sci Technol. 2003 May 1;37(9):1744-50.
Steroid estrogens profiles along river stretches arising from sewage treatment works discharges.

Williams RJ, Johnson AC, Smith JJ, Kanda R.

Centre for Ecology and Hydrology, Wallingford, Oxfordshire, OX10 8BB, UK. rjeh.ac.uk

Concentrations of estradiol, estrone, and ethinylestradiol were measured in the water column (daily for 28 or 14 days) and in the bed sediment (weekly over the same period) of the River Nene and the River Lea, U.K., upstream and downstream of sewage treatment works (STW). The concentrations of the three steroids in the STW effluents were also measured. Estrone was detected at the highest concentration and in almost all samples from the three STW effluents, concentrations ranging from <0.4 to 12.2 ng/L. Estradiol was also detected frequently (<0.4-4.3 ng/L), but ethinylestradiol was detected infrequently (<0.4-3.4 ng/L). Positive detections were only found for estrone in the sediment, and these seemed to be unrelated to the water column concentrations. Levels of estrone were clearly raised above background levels in the rivers as a result of the STW discharges. Levels of estradiol and ethinylestradiol were too close to their detection limits to assess the STW impact. River water estrone concentration declined downstream at a rate that was in excess of that due to dilution. The most likely cause of this decline is a combination of sorption and biodegradation equivalent to a first-order decay half-life of 2.5 days for the River Nene and 0.5 days for the River Lea.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12775044&dopt=Abstract estradiol




Endocrine. 2003 Jun;21(1):43-51.
Endogenous estrogen formation is neuroprotective in model of cerebellar ataxia.

Sierra A, Azcoitia I, Garcia-Segura L.

Instituto Cajal, C.S.I.C., Madrid, Spain.

The expression of aromatase, the enzyme that transforms testosterone into estradiol, was analyzed by reverse transcriptase polymerase chain reaction in the inferior olive of adult male rats. The expression of this messenger in the inferior olive suggests that this brain area may be able to synthesize estradiol. The neuroprotective role of estradiol in the inferior olive was then assessed in a model of cerebellar ataxia, achieved by the ip administration of 3-acetylpyridine (3-AP). In a first experiment, male Wistar rats were orchidectomized to diminish the plasmatic levels of testosterone, the direct precursor of estradiol. Immediately after castration, animals were implanted with a silicone tube that was either empty or filled with estradiol. One week later, animals were injected with 3-AP. Estradiol treatment resulted in a significant reduction in neuronal death in the olive. In a second experiment, animals were treated with fadrozole, an aromatase inhibitor, to assess the role of endogenous estradiol formation in neuroprotection. The results show that the inhibition of aromatase activity, and therefore the decrease in endogenous estrogen formation, increases the death in inferior olive. In conclusion, this study indicates that the inferior olive is a steroidogenic tissue and that olivary neurons are protected by exogenous and endogenous estradiol.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12777702&dopt=Abstract estradiol




Endocrine. 2003 Jun;21(1):53-8.
Chronic but not acute estradiol treatment protects against the neurodegenerative effects of N-methyl-D-aspartate receptor antagonists.

Dribben W, Nemmers B, Nardi A, Taylor G, Olney J, Farber N.

Department of Psychiatry, Division of Emergency Medicine, Washington University, St. Louis, MO 63110, USA. dribbensnotes.wustl.edu

Drugs that block NMDA receptors, thereby inducing an NMDA receptor hypofunctional (NRHypo) state, can cause a disseminated pattern of irreversible neurodegeneration. Based on several lines of evidence, an N-methyl-D-aspartate receptor hypofunction (NRHypo) mechanism has been postulated to contribute to neurodegenerative changes in Alzheimer disease (AD). Because estrogen putatively exerts a neuroprotective effect in AD, we examined whether estrogen protects against NRHypo-induced neurodegeneration. We administered estradiol benzoate in three separate experiments to adult female rats: (1) 100 microg subcutaneously as a onetime dose, (2) 100 microg bid twice daily for 4.5 or 14 d, and 3) 300 microg twice daily for 4.5 d. Two hours after the last estradiol dose, MK-801 was administered (0.5 mg/kg subcutaneously) to produce a robust neurotoxic injury. Controls received MK-801, but no estradiol. Four hours after administration of MK-801, the severity of injury was evaluated histologically by quantitative methods previously described. Compared to controls, a single dose of estradiol produced no change in the severity of injury (p = 0.24). Chronic treatment with estradiol was associated with a 25-35% reduction in the number of injured neurons (p < 0.05 in all cases). We conclude that chronic but not acute estradiol treatment reduces the severity of NRHypo-induced neurodegeneration.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12777703&dopt=Abstract estradiol




Endocrine. 2003 Jun;21(1):97-101.
Estradiol and dehydroepiandrosterone potentiate levodopa-induced locomotor activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkeys.

Belanger N, Gregoire L, Bedard P, Di Paolo T.

Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (CHUL), Quebec, Canada.

Six monkeys were rendered hemiparkinsonian with a unilateral injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. These monkeys displayed ipsilateral circling under basal conditions, and after dopaminergic stimulation with levodopa they decreased their ipsilateral circling and started turning to the contralateral side of their lesion. The effect of 17beta-estradiol and dehydroepiandrosterone (DHEA) was investigated in these animals. 17beta-Estradiol (0.1 mg/kg) added to a threshold dose of levodopa significantly potentiated contralateral circling (mean/30 min) compared to saline or threshold levodopa treatment whereas the duration of circling remained unchanged. DHEA (1-15 mg/kg) alone induced contralateral circling, compared to saline treatment, for 90 min. In addition, DHEA (1-15 mg/kg) potentiated the contralateral circling (mean/30 min) induced by a threshold dose of levodopa and did not change the duration of levodopa circling. A maximal response was observed with 1 or 5 mg/kg of DHEA combined with levodopa depending on the monkey. No correlation was found between the dose for the maximal DHEA response and baseline circling or threshold dose of levodopa. These results suggest that 17beta-estradiol or DHEA is able to potentiate locomotor activity of hemiparkinsonian monkeys. The DHEA doses investigated are similar to those presently used in humans. DHEA may be an alternative to 17beta-estradiol to modulate dopaminergic activity.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12777709&dopt=Abstract estradiol




Chin Med J (Engl). 2003 Mar;116(3):383-7.
Role of phosphatase PTEN in the activation of extracellular signal-regulated kinases induced by estradiol in endometrial carcinoma cells.

Zhang Y, Wei L, Wang J, Sun T.

Department of Gynecology, People's Hospital, Peking University, Beijing 100044, China. zyjbtamail.net.com

OBJECTIVES: To study extracellular signal-regulated kinase (ERK) activation in the endometrial carcinoma cell line Ishikawa with stimulation by 17-beta-estradiol, and to elucidate the role of phosphatase and tensin homologue (PTEN) and estrogen receptor (ER) subtype on the activation of ERKs. METHODS: Western blot was used to examine the expression of PTEN and PTEN (G129E) in Ishikawa cells after stable transfection as well as ERK activation in Ishikawa-EGFP, Ishikawa- PTEN and Ishikawa- PTEN (G129E) stimulated with various doses of 17-beta-estradiol for different lengths of time. Western blot was also used for examining the expression of ERalpha and ERbeta in NIH3T3 fibroblasts after transient transfection of pCXN2hERalpha and pCXN2hERbeta. Then, ERK activation was examined after stimulation with 17-beta-estradiol. RESULTS: 17-beta-estradiol activated ERK cascades (mainly ERK2) in Ishikawa cells. The activation of ERK increased gradually as concentration of 17-beta-estradiol also increased. The maximal activation of ERK2 took place 5 min after stimulation with 17-beta-estradiol. The activation of ERK2 was inhibited markedly by PTEN, but not by PTEN (G129E). 17-beta-estradiol activated ERK cascades in NIH3T3 fibroblasts after transient transfection of pCXN2hERalpha. CONCLUSIONS: 17-beta-estradiol activate ERK cascades in Ishikawa cells by integrating with ERalpha. Lipid phosphatase PTEN has an inhibitory role on the activation of ERK stimulated by 17-beta-estradiol in Ishikawa cells.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12781042&dopt=Abstract estradiol




Int J Dev Neurosci. 2003 Jun;21(4):225-33.
Enhancement of dendritic branching in cultured hippocampal neurons by 17beta-estradiol is mediated by nitric oxide.

Audesirk T, Cabell L, Kern M, Audesirk G.

Biology Department, University of Colorado at Denver, P.O. Box 173364, Denver 80217-3364, USA. taudesiarbon.cudenver.edu

Both 17beta-estradiol (E2) and nitric oxide (NO) are important in neuronal development, learning and memory, and age-related memory changes. There is growing evidence that a number of estrogen receptor-mediated effects of estradiol utilize nitric oxide as an intermediary. The role of estradiol in hippocampal neuronal differentiation and function has particular implications for learning and memory.Low levels of estradiol (10nM) significantly increase dendritic branching in cultured embryonic rat hippocampal neurons (158% of control). This study investigates the hypothesis that the estrogen-stimulated increase in dendritic branching is mediated by nitric oxide. We found that nitric oxide donors also produce significantly increased dendritic branching S-nitroso-N-acetylpenicillamine (SNAP: 119%; 2,2'-(hydroxynitrosohydrazino)bis-ethanamine (NOC-18): 128% of control). We then determined that the increases in dendritic branching stimulated by estradiol or by a nitric oxide donor were both blocked by an inhibitor of guanylyl cyclase. Dendritic branching was also stimulated by a cell permeable analog of cyclic guanosine monophosphate (dibutyryl-cGMP: 173% of control). Estradiol-stimulated dendritic branching was reversed by the nitric oxide scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl imidazoline-1-oxyl 3-oxide (carboxy-PTIO). This study provides evidence that estradiol influences the development of embryonic hippocampal neurons in culture by increasing the production of nitric oxide or by increasing the sensitivity of the neurons to nitric oxide. Nitric oxide in turn stimulates dendritic branching via activation of guanylyl cyclase.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12781790&dopt=Abstract estradiol [PubMed - indexed for




Kidney Int. 2003 Jul;64(1):290-4.
Pharmacokinetics of oral micronized beta-estradiol in postmenopausal women receiving maintenance hemodialysis.

Stehman-Breen C, Anderson G, Gibson D, Kausz AT, Ott S.

Division of Nephrology, Seattle VA Puget Sound Health Care System, Seattle, Washington 98108, USA. co.washington.edu

BACKGROUND: Although 11% of postmenopausal women with end-stage renal disease (ESRD) are prescribed hormone replacement therapy (HRT), the appropriate use remains poorly explored. Although there remains controversy surrounding the benefits of HRT, it may be of particular interest in this population, which has a high risk of bone loss and a fourfold increase in fracture risk compared to the general population. However, the appropriate dose of estrogen for use in postmenopausal women with ESRD is not known. The objective of this study was to evaluate the steady-state pharmacokinetics of oral micronized beta-estradiol in postmenopausal women with ESRD compared with postmenopausal women with normal renal function in order to determine equivalent dosing. METHODS: Six postmenopausal women with ESRD receiving maintenance hemodialysis and 6 healthy postmenopausal controls received 14 days of micronized beta-estradiol (1.0 mg for control, 0.5 mg for ESRD). Blood, urine, and dialysate samples were obtained during a dosage interval on day 14. Estradiol, estrone, albumin, and sex-hormone binding globulin (SHBG) concentrations were determined. Free estradiol concentrations were calculated using a previously described method. RESULTS: Women with ESRD had significantly lower serum albumin (610 +/- 31 micromol/L vs. 684 +/- 83 micromol/L) and SHBG (78 +/- 17 vs. 118 +/- 13 nmol/L) than control subjects. Total clearance of estradiol was not significantly different. Due to difference in binding, free estradiol concentrations were significant higher in ESRD women (53.2 +/- 17.7 pg/mL) than control women (43.5 +/- 8.7 pg/mL), despite receiving 50% of the dose. There was no significant diff