Anticancer Res. 2003 Mar-Apr;23(2B):1455-60.
mRNA expression of the type I growth factor receptors in the human breast cancer cells MCF-7: regulation by estradiol and tamoxifen.

Revillion F, Pawlowski V, Lhotellier V, Louchez MM, Peyrat JP.

Laboratoire d'Oncologie Moleculaire Humaine, Centre Oscar Lambret, 3 rue Frederic Combemale, BP 309, 59020 Lille, France. f-revilliolambret.fr

BACKGROUND: We recently confirmed, in a series of 365 human breast cancers, that EGFR and c-erbB-2 were associated with estradiol receptors (ER) and/or progesterone receptors (PgR)-negative tumors. Conversely, we demonstrated that c-erbB-3 and c-erbB-4 were positively related to ER and PgR. In the present paper, we simultaneously quantified, for the first time, the mRNA expression of these four receptors in response to estradiol and 4-hydroxy-tamoxifen in the prototypical ER-positive human breast cancer cell line MCF-7. MATERIALS AND METHODS: The mRNA expression of the type I growth factor receptors was quantified with a one-step real-time RT-PCR assay. RESULTS: Estradiol down-regulates the mRNA expression of the four receptors. The EGFR decrease is maximal (30% under the control) for 10(-11) M estradiol. For the three other receptors, the decrease (50% under the control) in mRNA expression is maximal with 10(-9) M. These effects are completely abolished by 4-OH tamoxifen at 10(-6) M. CONCLUSION: In MCF-7 cells, we demonstrate that c-erbB-4 is down-regulated by estradiol and up-regulated by 4-OH tamoxifen, and confirm that the three other receptors followed the same pattern of expression.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12820409&dopt=Abstract estradiol




Brain Cogn. 2003 Jul;52(2):231-8.
Sex differences in episodic memory: minimal influence of estradiol.

Yonker JE, Eriksson E, Nilsson LG, Herlitz A.

Department of Psychology, Stockholm University, Stockholm, Sweden.

Sex differences exist for several cognitive tasks and estrogen has been suggested to influence these differences. Eighteen men and 18 women were matched on age and estradiol level. Potential sex differences were assessed in episodic memory, semantic memory, verbal fluency, problem solving, and visuospatial ability. Significant sex differences, favoring women, were found for tasks assessing episodic memory. Correlations between estradiol level and cognitive performance were significant for face recognition in females. Since sex differences remained in verbal episodic memory tasks and face recognition despite matched levels of estradiol, circulating estradiol does not appear to be of paramount consequence for observed sex differences in episodic memory.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12821106&dopt=Abstract estradiol




Circulation. 2003 Jul 15;108(2):211-7. Epub 2003 Jun 23.
Diabetes undermines estrogen control of inducible nitric oxide synthase function in rat aortic smooth muscle cells through overexpression of estrogen receptor-beta.

Maggi A, Cignarella A, Brusadelli A, Bolego C, Pinna C, Puglisi L.

Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Disease, University of Milan, Italy. adriana.maggnimi.it

BACKGROUND: Previous reports from our group have shown that 17beta-estradiol reduces the synthesis and activity of inducible nitric oxide synthase (iNOS) in rat aortic smooth muscle cells (SMC) in response to inflammatory mediators. In this study, we investigated the effect of 17beta-estradiol on iNOS function in aortic SMC from streptozotocin-diabetic rats. METHODS AND RESULTS: Comparative analysis of NO release and of iNOS mRNA and protein content after 24-hour stimulation with a cytokine mixture revealed milder iNOS activation in diabetic than in control SMC. Furthermore, 17beta-estradiol dose-dependently blocked iNOS synthesis and activity in control but not in diabetic SMC. The defective estrogen response in diabetic SMC at 24 hours could not be attributed to reduced expression of estrogen receptors (ER). In fact, mRNA and protein levels of ERalpha and, to a greater extent, of ERbeta, were increased in diabetic compared with nondiabetic SMC. Cytokines decreased ERalpha and ERbeta expression in both groups. However, 17beta-estradiol dose-dependently restored the expression of ERalpha but further downregulated that of ERbeta, indicating a differential regulation of ER isoforms. CONCLUSIONS: Estrogenic control of iNOS was impaired in diabetic SMC. This was associated with a larger increase of ERbeta than of ERalpha protein, whereas 17beta-estradiol regulated the two isoforms in an opposite fashion. Thus, modifications in the estrogen modulation of iNOS and in the expression pattern of ER may be involved in diabetic vascular dysfunction.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12821541&dopt=Abstract estradiol [PubMed - indexed for




Clin Exp Pharmacol Physiol. 2003 Jul;30(7):489-94.
Effects of ovariectomy and 17 beta-oestradiol replacement on [Ca2+]i in female rat cardiac myocytes.

Curl CL, Wendt IR, Canny BJ, Kotsanas G.

Department of Physiology, Monash University, Melbourne, Victoria, Australia.

1. The present study investigated the effects of ovariectomy (OVX) and 17beta-oestradiol replacement on [Ca2+]i in rat freshly isolated cardiac myocytes. 2. Myocytes were isolated from the hearts of sham, OVX and OVX + 17beta-oestradiol-replaced female rats by enzymatic digestion with collagenase. Changes in [Ca2+]i in response to varied extracellular [Ca2+] were measured using the Ca2+-sensitive dye fura-2, with the contractile responses of each cell measured as cell shortening. 3. Increasing extracellular [Ca2+] resulted in increased [Ca2+]i in all three groups. Peak [Ca2+]i and the amplitude of the Ca2+ transient were significantly greater (P < 0.01) in cells from OVX animals compared with cells from both sham and 17beta-oestradiol-replaced OVX animals. 4. The time-course of decay of the Ca2+ transient was significantly faster (P < 0.02) in OVX cells compared with both sham and 17beta-oestradiol-replaced cells. In addition, time to 50% relaxation was significantly faster (P < 0.04) and extent of shortening significantly greater (P < 0.01) in OVX cells than in either sham or 17beta-oestradiol cells. 5. These data demonstrate clear differences in peak [Ca2+]i and the amplitude of the Ca2+ transient between OVX female rat cardiac myocytes compared with intact and 17beta-oestradiol-replaced OVX female rat cardiac myocytes. This suggests that oestrogen may play a long-term role in limiting Ca2+ entry into the cardiac myocyte.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12823264&dopt=Abstract estradiol




Alcohol Clin Exp Res. 2003 Jun;27(6):975-80.
Ethanol and estradiol modulate alternative splicing of dopamine D2 receptor messenger RNA and abolish the inhibitory action of bromocriptine on prolactin release from the pituitary gland.

Oomizu S, Boyadjieva N, Sarkar DK.

Endocrinology Program, Biomedical Division, Center of Alcohol Studies and Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, 08901, USA.

BACKGROUND: Several reports show evidence for the existence of high levels of prolactin (PRL) in alcoholic men and women. Previously we have shown that ethanol increases PRL release both in vivo and in vitro. How ethanol increases PRL release is not well understood. METHODS: In this study, we determined the effects of ethanol in the presence and absence of estradiol-17 beta on PRL messenger RNA (mRNA) levels, dopamine D2 receptor mRNA splicing, and the PRL-inhibitory response of a dopaminergic agent, bromocriptine, in the pituitary of Fischer-344 rats and in primary cultures of anterior pituitary cells. Real-time reverse transcriptase-polymerase chain reaction was used for mRNA detection, and radioimmunoassay was used for hormone detection. RESULTS: Estradiol and ethanol alone increased PRL mRNA expression in the pituitary gland. Ethanol also potentiated estradiol action on PRL mRNA expression in the pituitary. Determination of the D2 receptor splicing, by determining the changes in the percentage of D2 receptor mRNA expressed as its long form (D2L) and as its short form (D2S), revealed that both ethanol and estradiol altered D2 receptor splicing. Ethanol and estradiol, alone and together, increased the percentage of the D2L receptor but decreased the D2S receptor percentage. Similarly, ethanol and estradiol alone and in combination increased D2L, but decreased the D2S receptor percentage in primary cultures of pituitary cells. Evaluation of bromocriptine's inhibition of PRL release in primary cultures of pituitary cells indicated that ethanol reduced the abi