백서에서 난소절제술 시행후 전신골밀도와 말초혈액 및 골수 단핵구의 IL-1치의 변화에 관한 연구

김성한 啓明大學校 醫科大學 1997 계명의대학술지 Vol.16 No.1

Although the mechanism of bone resorption induced by estrogen deficiency is still controversial, recent studies have suggested that estrogen may modulate the secretion of bone resorption cytokines that are produced in the bone microenvionment and influence bone remodeling. Among them, IL-1 promotes bone resorption by stimulation the activity of mature osteoclasts and the differentiation of osteoclast precursors and the production of cytokines are mediated by estrogen. The purpose of the this study was to evaluate the effect of ovariectomy on bone mineral density and levels of IL-1 in the culture media of bone marrow and peripheral blood monocytes. The experimental animals were 16 female Sprague-Dawley rats that were 8 weeks of age and weighed an average of 186.8gm at the beginning of the study. Bilateral ovariectomy was performed form a vental approach in all rats. Bone mineral density(BMD) of the total body and IL-1 levels in culture media of bone marrow and peripheral blood monocytses were measured before and 8 weeks after ovariectomy with DPX-L and ELISA assay, respectively. Serum levels of LH, FSH and E were measured by RIA assay. BMD of total body was lower after ovariectomy(0.24±0.04g/cm2) than before ovariectomy (0.27±0.03g/cm2)(p<0.05). Serum levels of LH, FSH were higher after ovariectomy(0.87±0.36mlU/ml, 9.47±1.26 mlU/ml) than before ovariectiomy (0.10±0.06mlU/ml, 2.09±0.41 mlU/ml)(p<0.01) and serum level of E was lower after ovariectomy(10.98±8.71pg/ml) than before ovariectomy(7350.77±417.29 pg/ml)(0.01), respectively. Levels of IL-1 in culture media of bone marrow monocytes were higher after ovariectomy(25.4753.54 pg/ml) than before ovariectomy(9.83±1.10 pg/ml)(p<0.01), but there were no statistically significant differences in culture media of the peripheral blood monocytes(before ovariecomy: 10.59±1.03 pg/ml; after ovariectomy: 11.17±1.29 pg/ml). It is possible that the increased production of IL-1 in estrogen deficiency induced by ovariectomy occurs in the bone microenvironmnet and this cytokine may play a critical role in inducing bone loss.

흰쥐에서 난소절제술 시행후 대퇴 골밀도와 말초혈액 및 골수 TNF-α 의 변화에 관한 연구

김성한 啓明大學校 醫科大學 1997 계명의대학술지 Vol.16 No.1

Although the mechanism of the increase in bone resorption induced by estrogen deficiency is still controversial, recent studies have suggested that estrogen may modulate the secretion of bone resorption cytokines that are produced in the bone microenvironment and influence bone remodeling. Among them, TNF-α promotes bone resorption by stimulating the activity of mature osteoclasts and osteoclastogenesis, and the production of this cytokine is mediated by estrogen. We performed thsi study to evaluate the effect of oveariectomy on femur bone mineral density and levels of TNF-α in the culture media of bone marrow monocytes. The experimental animals were 15 female Sprague-Dawley rats that were 6 weeks of age and weighed an average of 172.8 gm at the beginning of the study. Bilateral ovariectomy were performed in all rats from a vental approach. Bone mineral density(BMD) of femur and levels of TNF-α of culture media of peripheral blood and bone marrow monocytes were measured before and 8 weeks after operation with using DPX-L and ELISA assay, respectively. Serum levels of LH. FSH, E2 were measured by RIA assay. BMD of femur was lower after ovariectomy(0.20±0.03 g/cm2) than before ovariectomy(0.25±0.06) g/cm2)(p<0.05). Serum levels of LH, FSH were higher after ovariectiomy(0.71±0.29mu/ml. 10.27±1.21 mu/ml) than before ovariectomy(0.17±0.04 mU/ml. 2.79±0.61 mlU/ml)(p<0.01) and serum level of E2 was lower after ovariectomy(6.37±4.75 Pg/ml) than before ovariectomy(7159.16±385.82 pg/ml)(p<0.01), respectively. Levels of TNF-α in culture media of bone marrow monocytes were higher after ovariectoy(59.26±5.65 pg/ml) than before ovariectomy(23.37±4.13 pg/ml)(p<0.01), but there were no statistically significant differences in culture media of the peripheral blood monocytes(before ovariectomuy: 22.96±3.62 pg/ml; after ovariectomy: 23.55±2.98pg/ml)(p>0.05). It is possible that increased production of TNF-α in estrogen deficieny induced by ovariectomy occures in the bone microenvironment and cytokine may play a critical causal role in inducing bone loss.

난소절제로 유발된 골다공증 시 흰쥐 갑상샘에 대한 조직학적 및 면역조직화학적 연구

김대영,구세광,이재현,장인호,이형식 한국임상수의학회 1998 한국임상수의학회지 Vol.15 No.2

In order to investigate the histological and immunohistochemical changes of thyroid glands, and serum osteocalcini estradiol, pmgesterone, follicular-stimulating hormone (FSH), and calcium levels in the osteoporotic rats induced by ovariectomy, normal(sham-operated group) and experimental groups(ovariectomized group) were divided. The experimental groups were subdivide6 to 5, 10, 15, and 20 weeks after ovariectomized groups. The histological structure of the thyroid gland were observed in normal structure throughout all experimental periods but the calcitonin-immunoreartive cells in the experimental groups were significantly decreased compared with normal groups and degranulations of calcitonin-immunoreactive cells were observed. Theses numbers were decreased with time after ovariectomy. However, the serum osteocalcin and FSH levels of experimental groups were significantly increased compared with normal groups and these levels were increased along with time after ovariectomy, but serum estradiol, progestemn and calcium levels of experimental group were significantly decreased compared with normal groups and these levels were decreased with time after ovariectomy.

Effects of 17β-estradiol on colorectal cancer development after azoxymethane/dextran sulfate sodium treatment of ovariectomized mice

Song, Chin-Hee,Kim, Nayoung,Lee, Sun Min,Nam, Ryoung Hee,Choi, Soo In,Kang, So Ra,Shin, Eun,Lee, Dong Ho,Lee, Ha-Na,Surh, Young-Joon Elsevier 2019 Biochemical pharmacology Vol.164 No.-

<P><B>Abstract</B></P> <P>Estrogen is known to have a protective effect in colorectal cancer (CRC) development. Previously, we reported the anti-inflammatory and antitumorigenic effects of 17β-estradiol (E2) in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated male mice. The aim of this study was to investigate whether ovariectomy in a female AOM/DSS mouse model increases colorectal tumorigenesis and whether tumorigenesis is reduced by estrogen supplementation after ovariectomy. Clinical symptoms and histological severity of colitis and the levels of inflammatory mediators were evaluated in the colon of AOM/DSS-treated ovariectomized (OVX) mice. The levels of E2, myeloperoxidase (MPO), and NF-κB-dependent cytokines (interleukin (IL)-1β and IL-6) were measured by ELISA. Furthermore, quantitative real-time (qRT) PCR and Western blot analysis were performed. Ovariectomy did not aggravate AOM/DSS-induced colitis at 2 weeks. At weeks 10 and 16, ovariectomy significantly increased tumor number and incidence rate in only the proximal colon after AOM/DSS treatment (F_AOM/DSS vs OVX_AOM/DSS), and these increases were significantly reduced by E2 supplementation (OVX_AOM/DSS vs OVX_AOM/DSS/E2). However, ovariectomy did not affect CRC development in the distal colon (F_AOM/DSS vs OVX_AOM/DSS). At week 2, E2 administration to AOM/DSS-treated OVX mice attenuated the histological severity of colitis by decreasing the protein and/or mRNA levels of estrogen receptor alpha (ERα) and NF-κB-related mediators (i.e., COX-2, TNF-α, and IL-6) and by enhancing estrogen receptor beta (ERβ) and nuclear Nrf2 protein expression and the mRNA expression of related antioxidant enzyme genes (i.e., HO-1, GCLC, GCLM, and NQO1). Endogenous estrogen in females protects against the development of proximal colon cancer, and exogenous E2 replacement in OVX female mice showed protective effects against AOM/DSS-induced colitis and carcinogenesis. The mechanism could involve modulating ERs-, NF-κB- and Nrf2-mediated pathways.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

17Beta-Estradiol Inhibits Calcium-Activated Potassium Channel Expressions in Rat Whole Bladder

김덕윤,양은경 대한배뇨장애요실금학회 2016 International Neurourology Journal Vol.20 No.1

Purpose: To investigate the effect of estrogen on the expression of calcium-activated potassium (KCa) channels in an overactive bladder rat model. To this end, mRNA and protein levels of KCa channel subtypes in the bladder of ovariectomized rats were measured by reverse transcription polymerase chain reaction and western blotting, respectively. Methods: Ten-week-old female Sprague-Dawley rats were divided randomly into 3 groups: sham-operated control group (n=11), ovariectomy group (n=11), and the group treated with estrogen after ovariectomy (n=12). Rats in the last group were subcutaneously injected with 17β-estradiol (50 μg/kg) every other day for 2 weeks, whereas rats in the other 2 groups received vehicle (soybean oil) alone. Two weeks after treatment, the whole bladder was excised for mRNA and protein measurements. Results: Protein levels of the large-conductance KCa (BK) channels in the ovariectomy group were 1.5 folds higher than those in the sham-operated control group. However, the protein levels of the other KCa channel subtypes did not change significantly upon bilateral ovariectomy. Treatment with 17β-estradiol after ovariectomy restored BK channel protein levels to the control value. In contrast, BK channel mRNA levels were not significantly affected by either ovariectomy alone or 17β-estradiol treatment. The small-conductance KCa type 3 channel (SK3) mRNA and protein levels decreased to 75% of control levels upon 17β-estradiol treatment. Conclusions: These results suggest that 17β-estradiol may influence urinary bladder function by modulating BK and SK3 channel expression.

Histomorphometric Analysis of the Spine and Femur in Ovariectomized Rats Using Micro-Computed Tomographic Scan

Shin, Yong-Hwan,Cho, Dae-Chul,Yu, Song-Hee,Kim, Kyoung-Tae,Cho, Hee-Jung,Sung, Joo-Kyung The Korean Neurosurgical Society 2012 Journal of Korean neurosurgical society Vol.52 No.1

Objective : The purpose of this study was to evaluate the different patterns of bone loss between the lumbar spine and the femur after ovariectomy in rats. Methods : Twenty-four female Sprague-Dawley rats underwent a sham operation (the sham group) or bilateral ovariectomy (the ovariectomized group). Four and eight weeks after operation, six rats from each of the two groups were euthanized. Serum biochemical markers of bone turnover including osteocalcin and alkaline phosphatase (ALP), which are sensitive biochemical markers of bone formation, and the telopeptide fragment of type I collagen C-terminus (CTX), which is a sensitive biochemical marker of bone resorption, were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae and femur were determined by micro-computed tomography. Results : Ovariectomized rats were found to have higher osteocalcin, ALP and CTX levels than sham controls. Additionally, 8 weeks after ovariectomy in the OVX group, serum levels of osteocalcin, ALP and CTX were significantly higher than those of 4 weeks after ovariectomy. Bone loss after ovariectomy was more extensive in the 4th lumbar spine compared to the femur. Bone loss in the 4th lumbar spine was mainly caused by trabecular thinning, but in the femur, it was mainly caused by trabecular elimination. Conclusion : The present study demonstrates different patterns of bone loss between the 4th lumbar spine and the femur in ovariectomized rats. Therefore, when considering animal models of osteoporosis, it is important that bone sites should be taken into account.

The Effects of Carob (Ceratonia siliqua L.) on Emotional Behavior Impairment and Metabolic Disorders Induced by Estrogen Deficiency in Rats

Mohamed Ammari,Haifa Othman,Kaıs Rtibi,Mohsen Sakly,Hafedh Abdelmelek 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.9

Carob (Ceratonia siliqua L.) contains a wide variety of polyphenols with high antioxidant properties. In this study, we investigated the effects of aqueous extract of carob pods (AECP) on emotional behavior impairments and metabolic disorders in ovariectomized (OVX) rats. Female Wistar rats were assigned to three groups: group 1, control non-OVX rats; group 2, OVX rats; and group 3, OVX rats orally treated with AECP (500 mg/kg) for15 days after ovariectomy. Elevated plus-maze and open-field tests were performed on the 26th and 27th post-ovariectomy days, respectively. Afterwards, the rats were anesthetized and their serums were collected for biochemical analysis. We found that AECP improved emotional behavior impairments revealed by elevated plus-maze and open-field tests in OVX rats. Moreover, ovariectomy significantly increased triglyceride, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase levels in the serum. AECP administration significantly reversed ovariectomy-induced biochemical alterations. Thus, we suggest that the AECP may have an anxiolytic-like effect and prevent biochemical disorders associated with menopause or ovariectomy.

Changes of Somatostatin-Immunoreactive Cells on the Stomach of Ovariectomized Rats

Jeong Hyun Chang 대한의생명과학회 2009 Biomedical Science Letters Vol.15 No.1

The changes on the regional distributions and frequencies of somatostatin-immunoreactive (IR) cells in the fundus and pylorus of the stomach of osteoporotic Sprague-Dawley rats induced by ovariectomy were studied by immunohistochemical methods. The experimental animals were divided into two groups, one for non-ovariectomized group (Sham) and the other for ovariectomized group (OVX). Samples were collected from the fundus and pylorus regions at the 10 th week after ovariectomy or sham-operation. Somatostatin-IR cells were observed in both regions of the stomach regardless of ovariectomy. Most of these IR cells in the mucosa of the fundus or pylorus were generally spherical or spindle in shape (open type cell) while cells found in the gastric gland regions were round in shape (close type cell). Significantly lower number (P<0.01) of somatostatin-IR cells were detected in OVX as compared with Sham in the fundus and pylorus. In the present study, the density of somatostatin in the stomach was markedly decreased. Therefore, these changes in density of somatostatin-IR cells detected in this study may support the speculation that the development of gastrointestinal symptoms in osteoporosis such as impairments of calcium and some lipids, frequently encountered in patients with postmenopausal osteoporosis because the changes in gastrointestinal endocrine density would reflect the change in the capacity of producing these hormones and regulating gut motility and digestion.

Liver PPARα and UCP2 are Involved in the Regulation of Ovariectomy-Induced Adiposity and Steatosis by Swim Training

Sunhyo Jeong,Michung Yoon 대한의생명과학회 2010 Biomedical Science Letters Vol.16 No.4

It is suggested that ovariectomy induces body weight gain primarily in the form of adipose tissue in rodents. Since liver peroxisome proliferator-activated receptor α (PPARα) and uncoupling 2 (UCP2) are involved in the regulation of energy expenditure, it was investigated whether swim training regulates ovariectomy-induced adiposity and steatosis through liver PPARα and UCP2 activation in female ovariectomized mice, an animal model of postmenopausal women. Swim-trained mice had significantly decreased adipose tissue weights compared with sedentary control mice. Histological analysis showed that hepatic lipid accumulation was inhibited by swim training. Concomitantly, swim training significantly increased mRNA levels of PPARα and its target genes responsible for peroxisomal fatty acid β-oxidation, such as acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and thiolase in the liver. Moreover, swim training induced the mRNA expression of UCP2. These results suggest that swim training can effectively prevent adiposity and steatosis caused by ovariectomy, in part through activation of liver PPARα and UCP2 in female obese mice.

An Ovariectomy-Induced Rabbit Osteoporotic Model: A New Perspective

Nathan Robert Wanderman,Cindy Mallet,Hugo Giambini,Nirong Bao,Chunfeng Zhao,Kai-Nan An,Brett A. Freedman,Ahmad Nassr 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.1

Study Design: Experimental Animal Model. Purpose: The aim of our study was to validate a pure bilateral ovariectomy (OVX) female New Zealand white rabbit model of postmenopausal osteoporosis utilizing animal-sparing in vivo techniques for evaluating bone mineral density (BMD). We also sought to demonstrate that bilateral OVX in female New Zealand white rabbits can produce diminished BMD in the spinal column and simulate osteoporosis, without the need for adjuvant chemotherapeutic agents (i.e., no additional glucocorticosteroids or other drugs were used for stimulating accelerated BMD loss), which can be assessed by in vivo BMD testing. Overview of Literature: Multiple animal models of postmenopausal osteoporosis have been described. Rat ovariectomy models have been successful, but are limited by rats’ inability to achieve true skeletal maturity and a slight morphology that limits surgical instrumentation. Rabbit models have been described which do not have these limitations, but previous models have relied on adjunctive steroid therapy to achieve osteoporosis and have required animal sacrifice for bone mineral density assessment. Methods: Thirty-six skeletally mature female rabbits underwent bilateral OVX. BMD was measured using dual-energy X-ray absorptiometry on the metaphysis of the proximal tibia and distal femur, at baseline and 17 weeks postoperatively. Results: Mean BMD values were significantly reduced by 21.9% (p <0.05) in the proximal tibia and 11.9% (p <0.001) in the distal femur at 17 weeks. Conclusions: This study is the first to demonstrate a significant bone loss within four months of pure OVX in rabbits using animalsparing validation techniques. We believe that this OVX model is safe, reproducible, and can be employed to longitudinally evaluate the effect of anti-osteoporosis therapeutics and surgical interventions.