scholarly journals 17β-Estradiol and Progesterone Regulate Expression of β-Amyloid Clearance Factors in Primary Neuron Cultures and Female Rat Brain

Endocrinology ◽  
2012 ◽  
Vol 153 (11) ◽  
pp. 5467-5479 ◽  
Author(s):  
Anusha Jayaraman ◽  
Jenna C. Carroll ◽  
Todd E. Morgan ◽  
Sharon Lin ◽  
Liqin Zhao ◽  
...  
Keyword(s):  
Sex Steroid ◽  
Female Rat ◽  
Converting Enzyme ◽  
Primary Neuron ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
17Β Estradiol ◽  
Β Amyloid ◽  
Aβ Clearance

Abstract The accumulation of β-amyloid protein (Aβ) is a key risk factor in the development of Alzheimer's disease. The ovarian sex steroid hormones 17β-estradiol (E2) and progesterone (P4) have been shown to regulate Aβ accumulation, although the underlying mechanism(s) remain to be fully elucidated. In this study, we investigate the effects of E2 and P4 treatment on the expression levels of Aβ clearance factors including insulin-degrading enzyme, neprilysin, endothelin-converting enzyme 1 and 2, angiotensin-converting enzyme, and transthyretin, both in primary neuron cultures and female rat brains. Our results show that E2 and P4 affect the expression levels of several Aβ clearance factors in dose- and time-dependent manners. Most notably, expression of insulin-degrading enzyme is significantly increased by both hormones in cultured neurons and in vivo and is inversely associated with the soluble Aβ levels in vivo. These findings further define sex steroid hormone actions involved in regulation of Aβ, a relationship potentially important to therapeutic approaches aimed at reducing risk of Alzheimer's disease.

scholarly journals Sex-specific regulation of collagen I and III expression by 17β-Estradiol in cardiac fibroblasts: role of estrogen receptors

2018 ◽  
Vol 115 (2) ◽  
pp. 315-327 ◽  
Author(s):  
Elke Dworatzek ◽  
Shokoufeh Mahmoodzadeh ◽  
Cindy Schriever ◽  
Kana Kusumoto ◽  
Lisa Kramer ◽  
...  
Keyword(s):  
Estrogen Receptor Alpha ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Pressure Overload ◽  
Collagen I ◽  
Female Rat ◽  
17Β Estradiol ◽  
Specific Regulation

Abstract Aims Sex differences in cardiac fibrosis point to the regulatory role of 17β-Estradiol (E2) in cardiac fibroblasts (CF). We, therefore, asked whether male and female CF in rodent and human models are differentially susceptible to E2, and whether this is related to sex-specific activation of estrogen receptor alpha (ERα) and beta (ERβ). Methods and results In female rat CF (rCF), 24 h E2-treatment (10−8  M) led to a significant down-regulation of collagen I and III expression, whereas both collagens were up-regulated in male rCF. E2-induced sex-specific collagen regulation was also detected in human CF, indicating that this regulation is conserved across species. Using specific ERα- and ERβ-agonists (10−7 M) for 24 h, we identified ERα as repressive and ERβ as inducing factor in female and male rCF, respectively. In addition, E2-induced ERα phosphorylation at Ser118 only in female rCF, whereas Ser105 phosphorylation of ERβ was exclusively found in male rCF. Further, in female rCF we found both ER bound to the collagen I and III promoters using chromatin immunoprecipitation assays. In contrast, in male rCF only ERβ bound to both promoters. In engineered connective tissues (ECT) from rCF, collagen I and III mRNA were down-regulated in female ECT and up-regulated in male ECT by E2. This was accompanied by an impaired condensation of female ECT, whereas male ECT showed an increased condensation and stiffness upon E2-treatment, analysed by rheological measurements. Finally, we confirmed the E2-effect on both collagens in an in vivo mouse model with ovariectomy for E2 depletion, E2 substitution, and pressure overload by transverse aortic constriction. Conclusion The mechanism underlying the sex-specific regulation of collagen I and III in the heart appears to involve E2-mediated differential ERα and ERβ signaling in CFs.

scholarly journals Insulin-degrading Enzyme Rapidly Removes the β-Amyloid Precursor Protein Intracellular Domain (AICD)

2002 ◽  
Vol 277 (16) ◽  
pp. 13389-13393 ◽  
Author(s):  
Dieter Edbauer ◽  
Michael Willem ◽  
Sven Lammich ◽  
Harald Steiner ◽  
Christian Haass
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Insulin Degrading Enzyme ◽  
Intracellular Domain ◽  
Degrading Enzyme ◽  
Β Amyloid

scholarly journals CALHM1 ion channel elicits amyloid-  clearance by insulin-degrading enzyme in cell lines and in vivo in the mouse brain

2015 ◽  
Vol 128 (13) ◽  
pp. 2330-2338 ◽  
Author(s):  
V. Vingtdeux ◽  
P. Chandakkar ◽  
H. Zhao ◽  
L. Blanc ◽  
S. Ruiz ◽  
...  
Keyword(s):  
Ion Channel ◽  
Cell Lines ◽  
Mouse Brain ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme

In vivo occupancy of female rat brain estrogen receptors by 17β-estradiol and tamoxifen

NeuroImage ◽  
2004 ◽  
Vol 23 (3) ◽  
pp. 1161-1167 ◽  
Author(s):  
D. Pareto ◽  
M. Alvarado ◽  
S.M. Hanrahan ◽  
Anat Biegon
Keyword(s):  
Estrogen Receptors ◽  
Rat Brain ◽  
Female Rat ◽  
17Β Estradiol

scholarly journals The influence of 17β-estradiol on annexin 1 expression in the anterior pituitary of the female rat and in a folliculo-stellate cell line

2007 ◽  
Vol 192 (2) ◽  
pp. 429-442 ◽  
Author(s):  
Evelyn Davies ◽  
Selma Omer ◽  
John F Morris ◽  
Helen C Christian
Keyword(s):  
Cell Line ◽  
Estrous Cycle ◽  
Anterior Pituitary ◽  
Stellate Cell ◽  
Ovariectomized Rats ◽  
Female Rat ◽  
Annexin 1 ◽  
17Β Estradiol ◽  
Estrous Cycle Stage

Annexin 1 (ANXA1) is a Ca2+- and phospholipid-binding protein that plays an important role as a mediator of glucocorticoid action in the host-defence and neuroendocrine systems. Sex differences in hypothalamo–pituitary–adrenal (HPA) axis activity are well documented and a number of studies have demonstrated that gonadal steroids act as regulators of HPA activity. The aim of this study was to investigate the effect of ovariectomyand 17β-estradiol replacement, and estrous cycle stage, on anterior pituitary ANXA1 content. The amount of anterior pituitary ANXA1 determined by western blotting varied with estrous cycle stage with a peak at estrus declining to a trough at proestrus. Ovariectomy resulted in a significant (P<0.05) decrease in anterior pituitary ANXA1 content. Administration of 17β-estradiol (1 μg/100 g) significantly (P<0.01) increased anterior pituitary ANXA1 expression in the ovariectomized animals. In contrast, there was no change in pituitary ANXA1 content in response to 17β-estradiol in adrenalectomized and adrenalectomized/ovariectomized rats. Treatment of TtT/GF cells, a folliculo-stellate cell line, with 17β-estradiol (1.8–180 nM) increased ANXA1 mRNA expression and increased the amount of ANXA1 protein externalized in response to a dexamethasone stimulus. These results indicate that 17β-estradiol stimulates ANXA1 expression in the anterior pituitary and in vivo an adrenal factor contributes to the mechanism of action.

Androgen- and Estrogen-Dependent Regulation of Insulin-Degrading Enzyme in Subcellular Fractions of Rat Prostate and Uterus

2005 ◽  
Vol 230 (7) ◽  
pp. 479-486 ◽  
Author(s):  
Daniel P. Udrisar ◽  
Maria I. Wanderley ◽  
Regina C. C. Porto ◽  
Carla L. P. Cardoso ◽  
Maria C. L. Barbosa ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Cytosolic Fraction ◽  
Male Rat ◽  
Insulin Degradation ◽  
Nuclear Fraction ◽  
Female Rat ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Uterine Growth ◽  
Rat Prostate

Innumerous data support the fact that insulin-degrading enzyme (IDE) is the primary enzymatic mechanism for initiating and controlling cellular insulin degradation. Nevertheless, insulin degradation is unlikely to be the only cellular function of IDE, because it appears that some cellular effects of insulin are mediated by IDE as a regulatory protein. Insulin-degrading enzyme shows a significant correlation with various cellular functions, such as cellular growth and differentiation, and the expression of IDE is developmentally regulated. Besides insulin, other substrates are also degraded by IDE, including various growth-promoting peptides. It has also been shown that IDE enhances the binding of androgen to DNA in the nuclear compartment. It is also known that the androgen hormones have a stimulatory effect on prostate growth, and that estradiol stimulates uterine growth. To establish whether IDE is regulated by a cellular prostate/uterine growth stimulus, the present study assessed whether IDE was modified in quantity and activity during proliferative conditions (castration + testosterone in the male rat, or castration + estradiol or the proestrus phase of the estrous cycle in the female rat) and autolysis (castration or the metestrus phase of the estrous cycle) using cytosolic and nuclear fractions of rat prostate and cytosolic fractions of rat uterus. The activity and amount of IDE decreased in the cytosolic fraction with castration and during metestrus, and increased with testosterone or estradiol treatment and during proestrus. In the nuclear fraction, the quantity of the IDE followed the same pattern observed in the cytosolic fraction, although without degradative activity. The data presented here suggest that IDE may participate in prostatic and uterine growth and that the testosterone or estradiol and/or prostate and uterus insulin-like growth factors may be important factors for the expression and regulation of IDE in the prostate and uterus

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