A Comparison of the Effects of Estrogen and Cimicifuga racemosa on the Lacrimal Gland and Submandibular Gland in Ovariectomized Rats

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Abstract

This study aims to observe the effects of estradiol and Cimicifuga racemosa on the lacrimal gland and submandibular gland of ovariectomized rats. We randomly divided 20 adult female SD rats into four groups—a sham-operated group (SHAM), ovariectomized (OVX) group, ovariectomized group treated with estradiol (OVX+ E), and ovariectomized group treated with the isopropanolic extract of Cimicifuga racemosa (OVX+ iCR). The SHAM group and OVX group used distilled water to instead the drugs. Two weeks after ovariectomy, the estradiol and iCR were administered for 4 weeks. Next, we used H&E staining and electron microscopy to observe any histological changes in the lacrimal and submandibular glands and immunohistochemical staining to observe the expressions of cleaved caspase-3 (Casp-3) and Cu-Zn SOD (superoxide dismutase). The H&E staining find that both drugs can prevent the cells of area from shrinkage in the two kinds of gland. But under the electron microscopy, estradiol and iCR have different efficacy. Estradiol is more effective at protecting mitochondria in lacrimal gland acinar cells than iCR, and iCR is more effective at suppressing endoplasmic reticulum expansion than estradiol. Both estradiol and iCR have a similar protective function on mitochondria in the submandibular gland. The protective function of the two glands may inhibit apoptosis by suppressing the expression of Casp-3. In addition, iCR increases the expression of Cu-Zn SOD in duct system of submandibular gland. The results suggest that both estradiol and iCR confer a protective effect on the lacrimal and submandibular glands of ovariectomized rats via different mechanisms.

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Modulation of antioxidant enzyme expression and function by estrogen.

Kerstin Laufs, Christian Grohé, O Adam … (2003)

Oxidative stress plays a pivotal role in the pathogenesis of atherosclerosis and can be effectively influenced by radical scavenging enzyme activity and expression. The vasoprotective effects of estrogens may be related to antioxidative properties. Therefore, effects of 17beta-estradiol on production of reactive oxygen species and radical scavenging enzymes were investigated. 17beta-estradiol diminished angiotensin II-induced free radical production in vascular smooth muscle cells (DCF fluorescence laser microscopy). 17beta-estradiol time- and concentration-dependently upregulated manganese (MnSOD) and extracellular superoxide dismutase (ecSOD) expression (Northern and Western blotting) and enzyme activity (photometric assay). Nuclear run-on assays demonstrated that 17beta-estradiol increases MnSOD and ecSOD transcription rate. Half-life of MnSOD mRNA was not influenced, whereas ecSOD mRNA was stabilized by estrogen. Copper-zinc SOD, glutathione-peroxidase, and catalase were not affected by estrogen. Estrogen deficiency in ovariectomized mice induced a downregulation of ecSOD and MnSOD expression, which was associated with increased production of vascular free radicals and prevented by estrogen replacement or treatment with PEG-SOD. In humans, increased estrogen levels led to enhanced ecSOD and MnSOD expression in circulating monocytes. Estrogen acts antioxidative at least to some extent via stimulation of MnSOD and ecSOD expression and activity, which may contribute to its vasoprotective effects.

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Estrogen Regulates Estrogen Receptors and Antioxidant Gene Expression in Mouse Skeletal Muscle

Kristen A. Baltgalvis, Sarah M Greising, Gordon Warren … (2010)

Background Estrogens are associated with the loss of skeletal muscle strength in women with age. Ovarian hormone removal by ovariectomy in mice leads to a loss of muscle strength, which is reversed with 17β-estradiol replacement. Aging is also associated with an increase in antioxidant stress, and estrogens can improve antioxidant status via their interaction with estrogen receptors (ER) to regulate antioxidant gene expression. The purpose of this study was to determine if ER and antioxidant gene expression in skeletal muscle are responsive to changes in circulating estradiol, and if ERs regulate antioxidant gene expression in this tissue. Methodology/Principal Findings Adult C57BL/6 mice underwent ovariectomies or sham surgeries to remove circulating estrogens. These mice were implanted with placebo or 17β-estradiol pellets acutely or chronically. A separate experiment examined mice that received weekly injections of Faslodex to chronically block ERs. Skeletal muscles were analyzed for expression of ER genes and proteins and antioxidant genes. ERα was the most abundant, followed by Gper and ERβ in both soleus and EDL muscles. The loss of estrogens through ovariectomy induced ERα gene and protein expression in the soleus, EDL, and TA muscles at both the acute and chronic time points. Gpx3 mRNA was also induced both acutely and chronically in all 3 muscles in mice receiving 17β-estradiol. When ERs were blocked using Faslodex, Gpx3 mRNA was downregulated in the soleus muscle, but not the EDL and TA muscles. Conclusions/Significance These data suggest that Gpx3 and ERα gene expression are sensitive to circulating estrogens in skeletal muscle. ERs may regulate Gpx3 gene expression in the soleus muscle, but skeletal muscle regulation of Gpx3 via ERs is dependent upon muscle type. Further work is needed to determine the indirect effects of estrogen and ERα on Gpx3 expression in skeletal muscle, and their importance in the aging process.

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Estrogen receptor-beta is the predominant estrogen receptor subtype in human oral epithelium and salivary glands.

Pirjo S. A. Mäkelä, S Savolainen, Larissa M. Laine … (2003)

Many studies have shown that the oral mucosa and salivary glands are sensitive to estrogen action. However, the expression of estrogen receptors (ERs) within these tissues is an area of controversy. ERs exist as two subtypes (ERalpha and ERbeta), and we hypothesized that the incongruity between ER expression and estrogen sensitivity may result from differential expression of ER subtypes in oral tissues. To test this hypothesis, we analyzed oral mucosal and salivary gland samples for ERalpha and ERbeta protein expression by immunohistochemistry from a cross-section of patients attending hospital for surgical problems of the head and neck. ERalpha was not detected in oral buccal and gingival epithelium or in salivary glands. In contrast, ERbeta was widely expressed at high levels in all oral tissues studied. Within these tissues, ERbeta was observed primarily in keratinocytes and salivary gland acinar and ductal cells. Our results demonstrating the expression of only the ERbeta subtype within oral tissues may explain the contradictory results from previous studies investigating ER expression in these tissues. Importantly, these results suggest that estrogens may act via ERbeta in oral tissues and explain the effect of hormonal changes on the oral mucosa as well as on saliva secretion and composition.

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Stephen L. Clarke: Role: Academic Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 20 March 2015

Publication date Collection: 2015

Volume: 10

Issue: 3

Electronic Location Identifier: e0121470

Affiliations

[1 ]Department of Stomatology, General Hospital of Chinese People’s Armed Police Forces, Beijing, China

[2 ]Department of Anatomy and Embryology, Peking University Health Science Center, Beijing, China

[3 ]Department of Obstetrics and Gynecology, Civil Aviation General Hospital, Beijing, China

[4 ]Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China

Oklahoma State University, UNITED STATES

Author notes

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: JJ LQ WB. Performed the experiments: YD. Analyzed the data: YD KN KW GC WW BJ YS JJ LQ WB. Contributed reagents/materials/analysis tools: JJ LQ WB. Wrote the paper: YD. Revised the article and approved the final version to be published: YD KN KW GC WW BJ YS JJ LQ WB.

* E-mail: jiajing1996@ 123456126.com (JJ); qinlihua88@ 123456163.com (LQ); bwp66@ 123456163.com (WB)

Article

Publisher ID: PONE-D-14-43602

DOI: 10.1371/journal.pone.0121470

PMC ID: 4368816

PubMed ID: 25793872

SO-VID: 4661869d-bfda-4f2c-8c30-15a0f9bedae5

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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

History

Date received : 23 October 2014

Date accepted : 7 February 2015

Page count

Figures: 14, Tables: 1, Pages: 22

Funding

This work was supported by Beijing Municipal Science and Technology Commission, grant number Z131100006813005 to JJ (URL: http://www.bjkw.gov.cn/n8785584/index.html). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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A Comparison of the Effects of Estrogen and Cimicifuga racemosa on the Lacrimal Gland and Submandibular Gland in Ovariectomized Rats

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Abstract

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Most cited references 46

Modulation of antioxidant enzyme expression and function by estrogen.

Estrogen Regulates Estrogen Receptors and Antioxidant Gene Expression in Mouse Skeletal Muscle

Estrogen receptor-beta is the predominant estrogen receptor subtype in human oral epithelium and salivary glands.

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