1.Serum estradiol levels decrease after oophorectomy in transmasculine individuals on testosterone therapy.
Sahil KUMAR ; Elise BERTIN ; Cormac O'DWYER ; Amir KHORRAMI ; Richard WASSERSUG ; Smita MUKHERJEE ; Neeraj MEHRA ; Marshall DAHL ; Krista GENOWAY ; Alexander G KAVANAGH
Asian Journal of Andrology 2023;25(3):309-313
Transmasculine individuals, considering whether to undergo total hysterectomy with bilateral salpingectomy, have the option to have a concomitant oophorectomy. While studies have evaluated hormone changes following testosterone therapy initiation, most of those patients have not undergone oophorectomy. Data are currently limited to support health outcomes regarding the decision to retain or remove the ovaries. We performed a retrospective chart review of transmasculine patients maintained on high-dose testosterone therapy at a single endocrine clinic in Vancouver, British Columbia, Canada. Twelve transmasculine individuals who underwent bilateral oophorectomy and had presurgical and postsurgical serum data were included. We identified 12 transmasculine subjects as controls, who were on testosterone therapy and did not undergo oophorectomy, but additionally matched to the first group by age, testosterone dosing regimen, and body mass index. There was a statistically significant decrease in the estradiol levels of case subjects postoophorectomy, when compared to presurgical estradiol levels (P = 0.02). There was no significant difference between baseline estradiol levels between control and case subjects; however, the difference in estradiol levels at follow-up measurements was significant (P = 0.03). Total testosterone levels did not differ between control and case subjects at baseline and follow-up (both P > 0.05). Our results demonstrate that oophorectomy further attenuates estradiol levels below what is achieved by high-dose exogenous testosterone alone. Correlated clinical outcomes, such as impacts on bone health, were not available. The clinical implications of oophorectomy versus ovarian retention on endocrinological and overall health outcomes are currently limited.
Female
;
Humans
;
Testosterone/therapeutic use*
;
Retrospective Studies
;
Ovariectomy
;
Hysterectomy/methods*
;
Estradiol
2.Protective Effect and Mechanism of Kuntai Capsule on Angiotensin II -Induced Hypertension in Ovariectomized Rats.
Xiao-Fen GE ; Sha-Sha LI ; Yan-Hua LIU ; Mei-Qiu LU ; Hui-Na SU ; Xin YANG ; Xiao-Wan SUN
Chinese journal of integrative medicine 2023;29(6):526-533
OBJECTIVE:
To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin II (Ang II)-induced hypertension in ovariectomized (OVX) rats.
METHODS:
Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+Ang II, OVX, OVX+Ang II, OVX+Ang II +E2, and OVX+Ang II +KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17- β -estradiol (E2, 1.2 mg/(kg·d)] respectively, Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+Ang II +KT, OVX+Ang II +E2) and the negative control group (OVX+Ang II). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting.
RESULTS:
Compared with the OVX+Ang II group, the systolic blood pressure of OVX+Ang II +KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II +KT group compared with the OVX+Ang II group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+Ang II +KT group, respectively (P<0.05). Compared with OVX+Ang II group, the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II +KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05).
CONCLUSION
KT could protect blood pressure of Ang II-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.
Female
;
Rats
;
Animals
;
Humans
;
Angiotensin II
;
Phosphatidylinositol 3-Kinases
;
Proto-Oncogene Proteins c-akt
;
Hypertension/drug therapy*
;
Estradiol/pharmacology*
;
Superoxide Dismutase
;
Ovariectomy
;
Mammals/metabolism*
3.Hippocampus is involved in 17β-estradiol exacerbating experimental occlusal inter- ference-induced chronic masseter hyperalgesia in ovariectomized rats.
Ying Ying FAN ; Yun LIU ; Ye CAO ; Qiu Fei XIE
Journal of Peking University(Health Sciences) 2022;54(1):40-47
OBJECTIVE:
To investigate the influence of chronic masseter hyperalgesia induced by 17β-estradiol (E2) and experimental occlusal interference (EOI) on underlying mechanism in hippocampus of ovariectomized (OVX) rats.
METHODS:
In the study, 32 OVX rats were randomly divided into 4 groups (8 rats/group): The control group was OVX group, and 0 μg/d E2 (vehicle) injection was started 7 d after OVX without EOI; in the experimental group (1) OVX + E2 group, 80 μg/d E2 injection was started 7 d after OVX without EOI; in the experimental group (2) OVX + EOI group, vehicle injection was started 7 d after OVX and EOI was applied 17 d after OVX; in the experimental group (3) OVX + E2 + EOI group, 80 μg/d E2 injection was started 7 d after OVX and EOI was applied 17 d after OVX. Bilateral masseter muscle mechanical withdrawal thresholds were measured before OVX, 7 days after OVX (before E2 injection), 17 days after OVX (10 days after E2 injection and before EOI) and 24 days after OVX (7 days after EOI). Immunofluorescence staining was used to reveal phospho-extracellular signal regulated kinase 1/2 (p-ERK1/2)-positive neurons in CA3 of hippocampus. The protein expression of p-ERK1/2 in hippocampus was detected using Western Blot.
RESULTS:
Compared with the control group [left side: (135.3±8.5) g, right side: (135.4±10.8) g], bilateral masseter muscle mechanical withdrawal thresholds of OVX+E2 group [left side: (113.3±5.6) g, right side: (112.5 ± 5.6) g] and OVX+EOI group [left side: (93.3±5.4) g, right side: 90.8±5.5) g] were decreased (P < 0.01). Bilateral masseter muscle mechanical withdrawal thresholds were significantly lower in OVX+E2+EOI group [left side: (81.2±6.2) g, right side: 79.8±7.7) g] than in the control, OVX+E2 and OVX+EOI groups (P < 0.05). The proportion of p-ERK1/2 positive neurons in the CA3 region of the hippocampus was increased in the control, OVX+E2, OVX+EOI and OVX+E2+EOI groups in turn, and the difference between the groups was statistically significant (P < 0.05). p-ERK1/2 protein expression was increased in the control, OVX+E2 and OVX+EOI groups in turn, but the difference was not statistically significant (P>0.05). p-ERK1/2 expression was significantly higher in OVX+E2+EOI group than in the other three groups (P < 0.05).
CONCLUSION
High concentration of E2 could exacerbated EOI-induced chronic masseter hyperalgesia in ovariectomized rats, and its central mechanism may be related to the upregulation of the phosphorylation of ERK1/2 in hippocampus.
Animals
;
Estradiol
;
Female
;
Hippocampus
;
Humans
;
Hyperalgesia/chemically induced*
;
Masseter Muscle
;
Ovariectomy
;
Rats
;
Rats, Sprague-Dawley
4.Effects of 275 nm and 310 nm ultraviolet irradiation on bone metabolism in ovariectomized osteoporotic rats.
Wei HE ; Si Wen YANG ; Juan CHEN ; Xiao Jun ZHU ; Zhi Zhong CHEN ; Wen Jun MA
Journal of Peking University(Health Sciences) 2022;54(2):236-243
OBJECTIVE:
To investigate the effect of 275 nm and 310 nm ultraviolet irradiation on ovariectomized rats' bone metabolism.
METHODS:
Twenty four 3-month-old female Sprague-Dawley (SD) rat were randomly divided into control group, sham operated group, 275 nm ultraviolet (UV) irradiation group and 310 nm UV irradiation group. Each group contained 6 rats. The rats in the two irradiation groups were treated with bilateral ovariectomy. The rats in sham operated group received sham operation (They were given the same back incision and a bit of par-ovarian fat were removed). Control group received no disposition. About 24 weeks after operation, all the rats received detailed bone mineral density (BMD) detection again. Detection regions include cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur. Next, osteopenia rats in 275 nm irradiation group were UV irradiated 275 nm with fixed illumination intensity (15 μW/cm2) everyday for 16 weeks. The osteopenia rats in 310 nm irradiation group were UV irradiated 310 nm with fixed illumination intensity (15 μW/cm2) everyday for 16 weeks. The backs of the rats were shaved regularly as irradiation area (6 cm×8 cm). After 16-week irradiation, all the rats' BMD of cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur were measured. At the end of the trial, all the rats' blood specimens were obtained and serum 25(OH)D, procollagen type Ⅰ N-peptide (PINP) and osteocalcin (OC) were measured.
RESULTS:
Compared with control group [(238.78±26.74) mg/cm3], the BMD of the whole body were significantly lower in 275 nm [(193.34±13.28) mg/cm3] and 310 nm [(191.19±18.48) mg/cm3] irradiation groups (P=0.002, P=0.001). There were no significant difference between sham operated group [(227.20±14.32) mg/cm3] and control group. After 16-week ultraviolet irradiation, the BMD of the whole body were significantly increased in 275 nm [(193.34±13.28) mg/cm3 vs. (221.68±25.52) mg/cm3, P=0.005] and 310 nm groups [(191.19±18.48) mg/cm3 vs. (267.48±20.54) mg/cm3, P < 0.001] after corresponding irradiation. The BMD of the four body regions (lumbar vertebra, proximal femur, mid femur and distal femur) had significantly increased after irradiation in 275 nm irradiation group. For 310 nm irradiation group, the BMD in cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur also had increased significantly after 310 nm ultraviolet irradiation. The concentration of serum 25(OH)D and OC was higher in 275 nm irradiation group than in control group [(46.78±5.59) μg/L vs. (21.32±6.65) μg/L, P=0.002;(2.05±0.53) U/L vs. (1.32±0.07) U/L, P=0.022]. Compared with the control, the concentration of serum 25(OH)D [(58.05±12.74) μg/L], OC [(2.04±0.53) U/L] and PINP [(176.16±24.18) U/L] was significantly higher (P < 0.001, P=0.015, P=0.005) in 310 nm irradiation group. However, there were no significantly difference between sham operated group and the control.
CONCLUSION
Both 275 nm and 310 nm ultraviolet could improve rats' vitamin D synthesis. Both 275 nm and 310 nm ultraviolet could improve osteopenia rats' bone condition. The irradiation of 310 nm might be more effective on bone condition improvement.
Animals
;
Bone Density
;
Bone Diseases, Metabolic/metabolism*
;
Female
;
Femur/metabolism*
;
Humans
;
Osteocalcin/metabolism*
;
Ovariectomy
;
Rats
;
Rats, Sprague-Dawley
6.Low-magnitude vibration promotes osteogenesis of osteoblasts in ovariectomized osteoporotic rats via the estrogen receptor
Guangguang ZHU ; Xiaoqin YU ; Jirui WEN ; Mingyue BAO ; Min TANG ; Jingge WANG ; Xueling HE ; Liang LI
Journal of Biomedical Engineering 2020;37(5):825-833
The purpose of this study was to investigate the effect of low-magnitude vibration on osteogenesis of osteoblasts in ovariectomized rats with osteoporosis via estrogen receptor α(ERα). The mRNA expression of osteogenic markers were examined with qRT-PCR, based on which the optimal vibration parameter for promoting osteogenesis was determined (45 Hz × 0.9 g, g = 9.8 m/s
Animals
;
Cell Differentiation
;
Estrogen Receptor alpha/genetics*
;
Female
;
Osteoblasts
;
Osteogenesis
;
Osteoporosis
;
Ovariectomy
;
Rats
;
Vibration
7.Effect of moxibustion at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) on bone morphology, metabolism and ERα of bone marrow mesenchymal stem cells in the ovariectomized rats.
Chang-Feng YAO ; Wu-Bin HU ; Ling HU ; Ya-Ling WANG ; Yu WANG ; Xian-Gang LIN ; Zi-Bing LIU
Chinese Acupuncture & Moxibustion 2019;39(3):287-292
OBJECTIVE:
To observe the effects of moxibustion at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) on bone morphology, metabolism and ERα of bone marrow mesenchymal stem cells (MSCs) in the ovariectomized rats and explore the underlying mechanism of moxibustion at Guanyuan (CV 4) and Sanyinjiao (SP 6) on the regulation of bone metabolism.
METHODS:
A total of 60 SD rats were randomized into a normal group (20 rats) and an ovariectomy group (40 rats). In the normal group, no any treatment was provided. In the ovariectomy group, the classical ovariectomy was adopted to set up the osteoporosis model. In the 13th week after ovariectomy, 10 rats were collected from each of the normal group and the ovariectomy group for model identification. After model identification, the ovariectomy group was subdivided into a model group, an estradiol group and a moxibustion group, 10 rats in each one. In the normal group and the model group, the gavage was provided with 2 mL 0.9% sodium chloride solution, once a day. In the estradiol group, the gavage was provided with 17β-estradiol 100 μg/(kg•d), once a day. In the moxibustion group, moxibustion was applied at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6), 15 min at each acupoint, once a day. The 6 treatments were as one course, with 1 day of interval, 12 courses were required. After 12-week intervention, the dual-energy X-ray was adopted to determine the bone mineral density (BMD) and bone mineral content of the whole body in living condition. After sacrificed, HE staining was adopted to observe femur structure, the enzyme-linked immunosorbent assay was to determine the absorbance of estradiol (E) and alkaline phosphatase (ALP) in serum and the real-time quantitative PCR method was to determine the mRNA expressions of ERα of MSCs in tibia and femur.
RESULTS:
Compared with the model group, BMD was increased obviously in the pelvis and spine in the moxibustion group and the estradiol group (<0.05, <0.01). Compared with the model group, the bone mineral content was higher in the rib, pelvis and spine in the moxibustion group and the estradiol group, there was no statistically significant difference (all >0.05). Compared with the model group, the bone trabeculas were stronger and well connected in the moxibustion group, indicated by HE staining. Compared with the model group, the concentrations of E in serum were increased obviously in the estradiol group and the moxibusiton group (both <0.01), and ALP concentrations reduced obviously in the estradiol group and the moxibustion group (both <0.001), the mRNA expressions of ERα in MSCs increased in the estradiol group and the moxibustion group (both <0.001).
CONCLUSION
Moxibustion at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) effectively increases BMD and bone strength in the ovariectomized rats and the mechanism may be related to the improvement of serum E concentration, the decrease of serum ALP concentration and the up-regulation of mRNA expression of ERα in MSCs.
Animals
;
Bone Density
;
Estrogen Receptor alpha
;
Female
;
Mesenchymal Stem Cells
;
Moxibustion
;
Oligopeptides
;
Ovariectomy
;
Rats
;
Rats, Sprague-Dawley
8.Cimicifuga heracleifolia is therapeutically similar to black cohosh in relieving menopausal symptoms: evidence from pharmacological and metabolomics studies.
Lan-Yun MIAO ; Thi Thanh Huyen CHU ; Ping LI ; Yan JIANG ; Hui-Jun LI
Chinese Journal of Natural Medicines (English Ed.) 2019;17(6):435-445
In the market of botanical dietary supplements, Cimicifuga heracleifolia (CH) has always been considered as an adulterated species of Cimicifuga racemosa (CR), a conventional American herb with promising benefits to counteract troubles arising from the menopause. However, the detailed comparison of their therapeutic effects is lacking. In present study, the pharmacological and metabolomics studies were comparatively conducted between CH and CR in ovariectomized (OVX) female rats. Specifically, estrogen-like, anti-hyperlipidemia and anti-osteoporosis effects were evaluated through measuring serum biochemical parameters, histopathological examination and micro computed tomography (Micro-CT) scanning. At the same time, a gas chromatography-mass spectrometry (GC-MS)-based serum metabolomics method was employed to profile the metabolite compositional changes. As a result, both CR and CH displayed anti-osteoporosis and anti-hyperlipemia on menopause syndrome. Meanwhile, their potentials in improving the OVX-induced metabolic disorders were discovered. In conclusion, these results demonstrated that CH is therapeutically similar to CR in relieving menopausal symptoms and CH could be considered as a promising alternative to CR instead of an adulterant in the market of botanical dietary supplements.
Animals
;
Cimicifuga
;
chemistry
;
classification
;
Dietary Supplements
;
analysis
;
Drug Evaluation, Preclinical
;
Female
;
Humans
;
Menopause
;
blood
;
drug effects
;
Metabolomics
;
Osteoporosis
;
blood
;
drug therapy
;
Ovariectomy
;
adverse effects
;
Phytotherapy
;
Plant Extracts
;
administration & dosage
;
blood
;
Rats
;
Rats, Sprague-Dawley
9.Protective capability of Astragalus (Huangqi) on auditory function in a rat model of estrogen deficiency.
Chinese Medical Journal 2019;132(1):106-108
Animals
;
Brain Stem
;
drug effects
;
Cochlea
;
drug effects
;
Cochlear Nerve
;
drug effects
;
Drugs, Chinese Herbal
;
pharmacology
;
Estrogens
;
deficiency
;
Female
;
Ovariectomy
;
Rats
;
Signal-To-Noise Ratio
10.Prolonged continuous infusion of teriparatide promotes bone metabolism in normal but not in castrated mice.
Minghan LI ; Youhua HE ; Guojun TONG ; Dehong YANG
Journal of Southern Medical University 2019;39(9):1045-1051
OBJECTIVE:
To investigate the effects of continuous pumping of teriparatide (TPTD) on bone metabolism in ovariectomized and normal mice and provide experimental evidence for the selection of animal models for studying the effects of TPTD and its related peptides on osteoclasts.
METHODS:
Twenty-four female C57BL mice (6-weeks old) were subjected to ovariectomy (OVX) or sham operation followed 7 days later by continuous pumping of TPTD or the solvent vehicle (VEH) a micropump (SHAM-VEH, SHAM-TPTD, OVX-VEH, and OVX-TPTD groups; =6). Two weeks later, the tibial and femoral bones were harvested for micro-CT scanning to measure the parameters of the tibia and the femoral cortical bone. Histopathological examinations of the tibial tissue were conducted using HE staining and TRAP staining and the number of osteoclasts and the growth plate thickness were determined. The serum Ca2 + levels of the mice were measured. The primary osteoblasts from the cranial bone were treated with estradiol (E2) and TPTD for 48 h, and the expressions of β-catenin and RANKL protein in the cells were analyzed.
RESULTS:
The trabecular bone mass of OVX mice was significantly lower than that of sham-operated mice ( < 0.05). Continuous TPTD pumping significantly reduced tibial cancellous bone mass and femoral cortical bone area in the sham-operated mice, while in the castrated mice, TPTD pumping increased the cancellous bone mass without changing the cortical bone area. TRAP staining showed that cancellous osteoblasts in the tibia increased significantly in the castrated mice as compared with the sham-operated mice, and TPTD pumping significantly increased the number of cancellous osteoblasts in the sham-operated mice ( < 0.05). In the primary cultured osteoblasts, treatment with both E2 and TPTD obviously lowered the expression of β-catenin and increased the expression of RANKL as compared with TPTD treatment alone.
CONCLUSIONS
Continuous pumping of TPTD promotes bone resorption in normal mice but does not produce obvious bone resorption effect in the ovariectomized mice, suggesting that castrated mice are not suitable models for studying the effect of TPTD and the related peptides on the osteoclasts.
Animals
;
Bone Density
;
Bone Density Conservation Agents
;
administration & dosage
;
pharmacology
;
Bone Resorption
;
drug therapy
;
Bone and Bones
;
drug effects
;
metabolism
;
Female
;
Growth Plate
;
drug effects
;
Mice
;
Mice, Inbred C57BL
;
Osteoclasts
;
drug effects
;
Ovariectomy
;
RANK Ligand
;
metabolism
;
Teriparatide
;
administration & dosage
;
pharmacology
;
beta Catenin
;
metabolism

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