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PubMed2004

Administration of estrogen shortly after ovariectomy mimics the anti-nociceptive action and change in 5-HT1A-like receptor expression induced by calcitonin in ovariectomized rats.

Although many clinical reviews are consistent with the view that hormone replacement therapy should be recommended for increasing bone mass of osteoporotic patients, calcitonin administration is preferable to hormone replacement therapy for the alleviation of pain accompanying osteoporosis, despite the fact that osteoporosis and the accompanying pain are accelerated by the reduction in estrogen levels. Distinct from the clinical view, animal studies have shown that estrogen treatment reduces ovariectomy-induced hyperalgesia, although the mechanism of this phenomenon is unknown. The discrepancy in clinical and animal study outcomes may be due to the timing of administration of estrogen after depletion of the hormone. To address this possibility, the anti-nociceptive effect of estrogen was compared with calcitonin using the tail withdrawal test in rats injected with estrogen or calcitonin at 3 weeks (short term) or 15 weeks (long term) after ovariectomy. Furthermore, we analyzed the change in [3H]8-OH-DPAT binding in the spinal cord, addressing whether estrogen exerts its anti-nociceptive effect by the expression of 5-HT receptors attributable to calcitonin-induced analgesia, as has been reported in our previous animal studies. The present study demonstrates that the administration of estrogen injected in the short term, but not long term, after ovariectomy mimicked the effects of calcitonin-induced anti-nociception and prevention of ovariectomy-induced decrease in 5-HT receptor expression in the spinal cord, although the effects of calcitonin were observed regardless of the timing of calcitonin injection. These results suggest that the estrogen receptor is downregulated gradually after ovariectomy. Disappearance of the estrogen receptor may be one of the reasons that estrogen is not recommended for the treatment for chronic pain associated with osteoporosis.

Analgesics↗
PubMed2006

Effect of ormeloxifene on ovariectomy-induced bone resorption, osteoclast differentiation and apoptosis and TGF beta-3 expression.

Effect of ormeloxifene, a multifunctional selective estrogen receptor modulator, on prevention of ovariectomy-induced bone resorption in retired breeder female rats, osteoclastogenesis using bone marrow cells from adult Balb/c mice cultured in presence of M-CSF and RANKL, osteoclast apoptosis using terminal deoxynucleotidyl transferase fragment end labeling and TGF beta-3 expression were investigated. Raloxifene, a benzothiophene reported to mimic effects of estrogen in bone, and estradiol were used for comparison. Ormeloxifene (10(-6) and 10(-8)M) significantly inhibited osteoclastogenesis (P<0.001 versus vehicle control) as evidenced by lower number of TRAP-positive osteoclasts in bone marrow cultures and caused apoptosis of osteoclasts. The effect was almost equivalent to that observed in presence of estradiol-17 beta, except that significant number of cells undergoing apoptosis was evident even at 10(-9)M concentration of estradiol-17 beta (P<0.001). Raloxifene, though inhibited osteoclastogenesis at much lower concentrations (10(-8) to 10(-12)M; P<0.001), failed to cause apoptosis of osteoclasts at any of the concentrations used. While ormeloxifene, raloxifene and ethynylestradiol significantly prevented ovariectomy-induced bone loss in vivo in retired breeder female rats, prevention of ovariectomy-induced decrease in BMD and trabecular network of proximal tibia, calcium and phosphorus levels in femur and tibia and prevention of ovariectomy-induced down-regulation of TGF beta-3 expression in lumbar vertebrae was of lower order in raloxifene- than ormeloxifene- or ethynylestradiol-supplemented females. Both the SERMs, however, produced considerable estrogenic effects at the uterine level as evidenced by increase in weight, total and endometrial area and luminal epithelial cell height; the effect being generally greater in raloxifene- than ormeloxifene-treated rats. Findings demonstrate that inhibition of estrogen-deficiency osteoporosis by ormeloxifene, as in case of estradiol, was mediated via inhibition of osteoclastogenesis, apoptosis of osteoclasts and up-regulation of TGF beta-3 expression. Raloxifene, though effective in inhibiting osteoclastogenesis in vitro at much lower concentrations, was not only less potent in preventing ovariectomy-induced bone loss in retired breeder female rats in vivo but also appeared to have a different mechanism of action than ormeloxifene and estradiol.

Animals↗
PubMed2005

Ovariectomy increases Na+, K+-ATPase, acetylcholinesterase and catalase in rat hippocampus.

In the present work we investigated the effect of ovariectomy on Na+, K+-ATPase and acetylcholinesterase (AChE) activities in rat hippocampus. We also studied some parameters of oxidative stress, namely total radical-trapping antioxidant potential (TRAP), thiobarbituric acid-reactive substances (TBA-RS), as well as the antioxidant enzyme activities superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities. Our hypothesis is that ovariectomy might cause alterations in essential enzyme activities necessary to brain normal functioning and that these chances could be caused by oxidative stress. Female adult Wistar rats were divided into three groups: (1) naive (control); (2) sham-operated; and (3) ovariectomized. Thirty days after ovariectomy rats were sacrificed. Results showed that rats subjected to ovariectomy presented a significant increase in Na+, K+-ATPase, AChE and CAT activities, but did not change the oxidative stress parameters studied when compared to sham or naive rats. Since ovariectomy mimics postmenopausal changes, our findings showing alteration in the activities of brain Na+, K+-ATPase, AChE and CAT may be related to problems in postmenopausal women.

Acetylcholinesterase↗
PubMed1998

The effect of aging and ovariectomy on mandibular condyle in rats.

STATEMENT OF PROBLEM: It is important for dentists to understand the effect of systemic hormonal change on the osseous oral structures. PURPOSE: This study examined the effect of aging and ovariectomy on rat mandibular condyle. MATERIAL AND METHODS: Seventy-two 120-day-old female Fischer rats were killed at 7, 14, 30, and 60 days after bilateral ovariectomy or sham surgery. As the baseline control group, eight animals were killed on day 0 without surgeries. Changes in the bone mineral density and bone marrow area were detected through dual-energy x-ray absorptiometry and soft x-ray photography, respectively. RESULTS: No significant difference of bone mineral density was found between the bilateral ovariectomy and sham surgery groups with dual-energy x-ray absorptiometry, probably because the thickness of cortical bone obscured any possible changes in trabecular bone. Age-related osteosclerotic changes were found in the sham group with soft x-ray photography. In contrast, the bilateral ovariectomy group showed little change in bone marrow area in relation to time course; on the other hand, the value of their bone marrow area became significantly larger than that of the sham surgery group from 14 days after ovariectomy onward. CONCLUSIONS: It was inferred that estrogen deficiency caused the significantly large marrow area found in the rat mandibular condyle. Although much more research is necessary, this study allowed us to speculate that osteoporotic changes may occur in the mandibular condyle of postmenopausal women.

Absorptiometry, Photon↗
PubMed2002

The effect of ovariectomy and long-term estrogen replacement on bladder structure and function in the rat.

PURPOSE The use of estrogen replacement therapy for treating postmenopausal urinary incontinence is a controversial topic. We examined the behavioral, cystometric and histological changes that occur with long-term estrogen depletion and supplementation in rat bladders to determine the role of menopause in lower urinary tract dysfunction. MATERIALS AND METHODS A total of 40 female Sprague-Dawley rats were placed into 1 of 3 groups, including bilateral ovariectomy, bilateral ovariectomy plus estrogen replacement and control. The estrogen replaced group received a 0.25 mg. 16-week sustained release pellet (Innovative Research of America, Sanasota, Florida) placed subcutaneously. After surgery voiding frequency and volume were measured in 24-hour periods by placing animals in metabolic cages. After 16 weeks the rats underwent catheterization and continuous cystometry. The bladder was then removed and stained with Gomori trichrome. The collagen-to-smooth muscle density ratio was calculated for each specimen using current imaging software. RESULTS There was no significant difference in voiding patterns in the 3 groups, as measured by volume and voiding frequency. Cystometric data showed a trend toward higher voiding pressure, threshold pressure, baseline pressure and mean inter-voiding pressure in the ovariectomy group compared with the estrogen and control groups, although there was no statistical significance. Histological studies showed a higher mean collagen-to-smooth muscle ratio plus or minus standard deviation in the ovariectomy group (0.807 +/- 0.204) than in the ovariectomy plus estrogen replacement (0.709 +/- 0.118) and control (0.700 +/- 0.129) groups (p <0.05). Furthermore, when histological and cystometric data were compared for individual samples, we found a direct correlation of mean inter-voiding pressure (a measure of bladder instability) with the collagen-to-smooth muscle ratio (p <0.05). CONCLUSIONS Long-term estrogen replacement is beneficial for treating postmenopausal urinary incontinence.

Animals↗
PubMed2002

Characterization of bone mineral composition in the proximal tibia of cynomolgus monkeys: effect of ovariectomy and nandrolone decanoate treatment.

Life postmenopausal women, ovariectomized cynomolgus monkeys (Macaca fascicularis) experience accelerated loss of bone mass. Treatment of ovariectomized monkeys with nandrolone decanoate results in an increase in bone mass to levels comparable to those of intact animals. The changes in bone composition that occur with these treatments, however, are less well characterized. In the present study, we used synchrotron Fourier-transform infrared microspectroscopy (FT-IRM) and curve-fitting methods to monitor specific changes at cortical, subchondral, and trabecular bone regions in the proximal tibia. Four groups were studied: (1) sham-operated (sham); (2) ovariectomized and treated with placebo for 2 years (ovx); (3) ovx + nandrolone decanoate for 2 years (NAN); and (4) ovx + nandrolone decanoate beginning 1 year after ovx (dNAN). The results demonstrate that ovariectomy and nandrolone treatment did not affect the degree of mineralization as defined by the phosphate/protein ratio, but acid phosphate content (HPO(4)(2-)) in cortical and subchondral bone was increased by ovariectomy, suggesting this bone to be less mature due to increased remodeling that occurs after ovariectomy. In the subchondral and cortical bone regions, ovariectomized monkeys showed a lower total carbonate content (CO(3)(2-)/matrix ratio) than sham controls, specifically due to the decrease in labile carbonate content. In the trabecular region, no change of carbonate content was observed. Treatment with nandrolone decanoate was found to restore the loss in carbonate, where the resulting mineral had a larger quantity of type B carbonate. Finally, we correlated carbonate content with dual-energy X-ray absorptiometry measurements, and found a positive correlation between bone mineral density and type A carbonate in bone, which is stoichiometrically related to the amount of calcium in bone. Therefore, the results presented herein identify significant differences in bone chemistry after ovariectomy and nandrolone treatment, which may help explain previous findings that, although nandrolone decanoate treatment increased bone mass, it could not reverse the decrease in bone strength due to ovariectomy.

Anabolic Agents↗
PubMedDate not supplied

Cerebral thrombosis and microcirculation of the rat during the oestrous cycle and after ovariectomy.

1. The effects of oestrogen on thrombogenesis and the cerebral microcirculation of the female rat were studied during the oestrous cycle and after ovariectomy. 2. Serum levels of oestradiol (E2) and plasma concentrations of nitric oxide (NO) metabolites were significantly greater at pro-oestrus than at dioestrus. Blood vessel diameter, mean red cell velocity, wall shear rate and blood flow at pro-oestrus were significantly higher than at dioestrus. Thrombotic tendency, assessed using a He-Ne laser-induced thrombosis model, was significantly decreased at pro-oestrus compared with dioestrus. 3. The long-term deprivation of oestrogen by ovariectomy significantly depressed serum levels of E2 and plasma concentrations of NO metabolites. Thrombotic tendency was significantly increased 4 weeks after ovariectomy. Vessel diameter, mean red cell velocity, wall shear rate and blood flow in pial arterioles were significantly reduced after ovariectomy. 4. Exogenous administration of oestrogen (17 beta-oestradiol) after surgery reversed the increased thrombotic tendency mediated by ovariectomy. 5. These results strongly indicate that oestrogen mediates beneficial effects on the cerebral microcirculation and moderates cerebral thrombotic mechanisms in the female rat.

Animals↗
PubMedDate not supplied

Bilateral laparoscopic ovariectomy in standing mares: 22 cases.

OBJECTIVE: To describe a technique for laparoscopic bilateral ovariectomy in standing mares and report the outcome of 22 clinical cases. STUDY DESIGN: Prospective study. ANIMALS OR SAMPLE POPULATION: A total of 22 mares between 4 and 23 years of age, weighing between 360 and 600 kg. METHODS: Mares with normal ovaries, as determined by palpation per rectum, were restrained in standing stocks and sedated with detomidine (0.01 to 0.02 mg/kg intravenously [i.v.]) and butorphanol (0.01 to 0.02 mg/kg i.v.). The laparoscope and instrument insertion sites were infiltrated with 2% lidocaine before incision. One laparoscope portal and two instrument portals were located in each paralumbar fossa. Ovariectomy was accomplished by intracorporeal dissection and ligation of the ovarian pedicles. The two instrument portals in each flank were ultimately connected resulting in a 4 to 5 cm laparotomy to facilitate ovarian removal. RESULTS: No major operative or postoperative complications occurred. Minor complications included incomplete hemostasis of an ovarian pedicle with a single ligature (three mares), transient inappetence, pyrexia and incisional infection. Owner satisfaction and cosmetic results were considered excellent. CONCLUSIONS: Standing laparoscopic ovariectomy appears to eliminate many of the potential complications associated with traditional surgical methods for ovariectomy and avoids the risk of general anesthesia. CLINICAL RELEVANCE: This technique requires minimal laparoscopic instrumentation and will provide surgeons with an alternative approach for bilateral ovariectomy in mares.

Animals↗
PubMedDate not supplied

Laparoscopic ovariectomy using sequential electrocoagulation and sharp transection of the equine mesovarium.

OBJECTIVE: To describe in horses and ponies a laparoscopic ovariectomy technique facilitated by electrosurgical instrumentation. STUDY DESIGN: Elective ovariectomy was performed in 23 mares using laparoscopic electrosurgical instrumentation. ANIMALS OR SAMPLE POPULATION: Twenty-three mares (13 horses, 10 ponies), aged from 2 to 21 years and weighing 90 to 545 kg. METHODS: Food was withheld for a minimum of 12 hours. Mares were sedated with detomidine hydrochloride (0.02 to 0.03 mg/kg) or xylazine hydrochloride (0.5 to 1.0 mg/kg). Excluding the pony mares, all other mares were restrained in stocks. Portal sites in the paralumbar fossa region were desensitized with 2% mepivacaine. Abdominal insufflation was achieved through a teat cannula positioned in the ventral abdomen or a Verres-type needle placed through the paralumbar fossa. After trocar and laparoscope insertion, the ipsilateral ovary and mesovarium were identified, and the mesovarium, tubal membrane, and proper ligament were infiltrated with 2% mepivacaine. The mesovarium was coagulated using bipolar or monopolar electrosurgical forceps and transected sequentially from cranial to caudal until the ovary was completely freed and then removed. The contralateral ovary was removed in a similar fashion through the opposite paralumbar fossa. RESULTS: Bipolar and monopolar electrosurgical forceps were easy to use and provided adequate coagulation of vessels within the mesovarium. Two mares were euthanatized after the procedure for unrelated reasons. One mare had mild signs of colic 24 hours after ovariectomy. In 1 pony mare, the incision used to remove one ovary dehisced on the 5th postoperative day and was allowed to heal by second-intention. No long-term complications had occurred in 11 horses and 10 ponies, 6 to 24 months after surgery. CONCLUSION: Laparoscopic ovariectomy and hemostasis of the mesovarium can be easily accomplished using electrosurgical instrumentation. CLINICAL RELEVANCE: Standing laparoscopic ovariectomy, using electrosurgical instrumentation, is an effective and safe technique to provide hemostasis of the mesovarium in mares.

Animals↗
PubMed1995

Effect of ovariectomy and sex hormone replacement on glutathione and glutathione-related enzymes in rat hepatocarcinogenesis.

The effects of ovariectomy and hormone replacement in control and carcinogen treated female rats were investigated by measuring whole blood and liver glutathione (WGSH, HGSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GRx) and histological evaluation. Hepatocarcinogenesis was induced by diethylnitrosamine and 2-acetylaminofluorene. In control rats not receiving carcinogen, ovariectomy significantly increased the GST and GRx activities. Replacement with either estrogen or progesterone reduced the GST activities to below intact female values whereas replacement of both hormones together brought the GST activities to that of intact females. GRx activities were brought to intact female values by replacement with estrogen or progesterone, either singly or in combination. Neither ovariectomy nor sex hormone/s replacement influenced the levels of WGSH, HGSH and GPx activities. Carcinogen administration to intact rats increased all the parameters measured. Ovariectomized rats treated with carcinogen showed lower GPx and GRx activities at 2 mths. However, replacement with either progesterone or combined estrogen and progesterone increased GPx and GRx activities to original values. On the other hand GST and GPx activities in ovariectomized rats which had carcinogen treatment were lower than intact rats after 5 mths. Replacement with hormones either singly or both brought GST and GPx activities up to intact rat levels receiving carcinogen. The levels of WGSH, HGSH and GRx activities (5 mths) in carcinogen treated rats were not influenced by ovariectomy and/or hormone/s replacement. The results from this study suggested that ovariectomy reduced the severity of hepatocarcinogenesis which was restored by sex hormone/s replacement.

2-Acetylaminofluorene↗
PubMed2004

Effects of ovariectomy on the neuroendocrine axes regulating reproduction and energy balance in young cynomolgus macaques.

Degeneration of the ovary in middle-aged women results in castrate levels of ovarian steroids and increased gonadotropin secretion from the anterior pituitary gland. Ageing in women is also accompanied by significant changes in energy homeostasis. We have observed alterations in hypothalamic morphology and gene expression in older women, including hypertrophy and increased gene expression of neurokinin B (NKB) neurones, elevated levels of gonadotropin releasing-hormone (GnRH) mRNA and decreased numbers of neurones expressing pro-opiomelanocortin (POMC) mRNA. To determine if loss of ovarian steroids could produce comparable changes in gene expression in young primates, we measured the effects of ovariectomy on NKB, GnRH and POMC gene expression in young cynomolgus monkeys. We also measured serum leptin and body weight to examine the consequences of ovariectomy on energy balance. NKB neurones in the infundibular nucleus of ovariectomized monkeys were larger, more numerous and displayed increased levels of NKB mRNA compared to those of intact controls. Moreover, ovariectomy increased the number of neurones expressing GnRH gene transcripts and elevated serum luteinizing hormone. By contrast, several parameters related to energy balance, including POMC gene expression, serum leptin and body weights, were unchanged by ovariectomy. Thus, the rise in NKB and GnRH gene expression in older women was simulated by ovariectomy in monkeys, but the changes in POMC gene expression and energy balance were not. This study provides strong support for the hypothesis that ovarian failure contributes to the increased NKB and GnRH gene expression observed in postmenopausal women.

Animals↗
PubMed1991

Osteopenia caused by ovariectomy in young female rats and prophylactic effects of 1,25-dihydroxyvitamin D3.

Young female rats were subjected to either bilateral ovariectomy or sham operation. One group of ovariectomized (ovx) animals was treated with the vitamin D metabolite 1,25(OH)2D3 after surgery. The effects of ovariectomy and 1,25(OH)2D3 treatment on different markers of bone formation (serum alkaline phosphatase, serum bone gla protein) and bone resorption (fasting urinary hydroxyproline) were determined. All rats were euthanized at 7 weeks post ovariectomy and their first lumbar vertebra were processed undecalcified for quantitative bone histomorphometry. A significant decrease in cancellous bone mass was noted in ovx compared with sham-operated rats. This bone loss was associated with increased biochemical markers of bone formation and bone resorption. Furthermore, ovariectomy led to elevated osteoblast perimeter and osteoid parameters as well as an increased osteoclast number. These data indicate that young growing rats develop osteopenia 7 weeks after ovariectomy which goes along with an accelerated bone turnover. Bone gla-protein, alkaline phosphatase and hydroxyproline can be useful markers in studies with ovx rats. Treatment with 1,25(OH)2D3 led to a lowered urinary hydroxyproline excretion and a significant decrease of osteoclast number whereas histomorphometrical indices of bone formation were nearly unchanged. Cancellous bone mass increased significantly in ovx rats treated with 1,25(OH)2D3 compared with non-treated rats. These results suggest that 1,25(OH)2D3 has a prophylactic effect with regard to bone loss in ovx rats which refers to a diminished bone resorption in the high bone turnover condition of ovx animals.

Animals↗
PubMedDate not supplied

Laparoscopic ovariectomy using the endo-GIA stapling device and endo-catch pouches and evaluation of analgesic efficacy of epidural morphine sulfate in 10 mares.

OBJECTIVE: To evaluate use of ENDO-GIA staples and ENDO-Catch pouches for ovariectomy in mares and to evaluate the efficacy of epidural morphine analgesia. STUDY DESIGN: Randomized clinical trial. ANIMALS: Mares (n = 10) with normal ovaries. METHODS: An Endo-GIA II stapler (United States Surgical Corp., Norwalk, CT) was used to amputate the ovaries bilaterally, in standing mares, and Endo-Catch II pouches (United States Surgical Corp.) were used for retrieval. Epidural morphine was used in 5 mares, and procedure duration, volume of lidocaine required to desensitize the ovarian pedicle, and sedation were compared with horses not administered epidural morphine. RESULTS: Use of the Endo-GIA II stapling device was an easy and an efficient method of ovariectomy, which was facilitated by use of epidural morphine. For the epidural group, the mean (+/-SD) surgical time was 69.2 +/- 10.2 minutes compared with 124.4 +/- 21.2 minutes for mares not administered morphine. Less systemic sedation was required for mares administered epidural morphine. CONCLUSIONS: Minimal ovarian manipulation was required to apply the stapler, hemorrhage was slight, and none of the mares had complications. Epidural morphine provided effective analgesia, improving patient comfort, and reduced the sedation needed to perform ovariectomy. CLINICAL RELEVANCE: Endo-GIA II staples are an efficient method for ovariectomy in normal mares. Epidural morphine should be considered to facilitate ovariectomy because less sedation and local anesthetic administration is required.

Analgesia, Epidural↗
PubMedDate not supplied

Laparoscopic ovariectomy in mares using a polyamide tie-rap.

OBJECTIVE: To describe use of a polyamide tie-rap to ligate the mesovarium during standing laparoscopic ovariectomy in mares. STUDY DESIGN: Prospective study. ANIMALS: Ten mares. METHODS: Bilateral ovariectomy was performed in 10 mares. Standing laparoscopic ovariectomy was performed using 3 portals in the paralumbar fossa. A commercial polyamide tie-rap was prepared as a loop and marked with 4 colored lines close to the buckle, to enable us to check whether the loop was tightened securely. The ovary was grasped with forceps and after the mesovarium was minimally transected cranially and caudally, the loop of the tie-rap was inserted in the abdomen and placed around the mesovarium. It was firmly tightened, until at least 3 of the 4 marks were visible, then the end of the tie-rap was cut. The ovary was transected and removed through an enlarged 3rd portal. The contralateral ovary was removed similarly through the opposite paralumbar fossa. Repeat laparoscopy was performed in 8 mares, 2, 3, 4, and 12 weeks later. RESULTS: None of the mares had postoperative discomfort. On repeat laparoscopy, there was complete encapsulation of the stump and tie-rap after 3-4 weeks. In 2 mares, an adhesion between the left stump and the mesentery of the descending colon was observed. CONCLUSION: Ligation of the mesovarium can be easily and safely performed using a polyamide tie-rap during standing laparoscopic ovariectomy in mares. CLINICAL RELEVANCE: Standing laparoscopic ovariectomy using a polyamide tie-rap is a safe, technically easy and reliable surgical procedure in the mare.

Animals↗
PubMed2006

Ovariectomy worsens secondary hyperparathyroidism in mature rats during low-Ca diet.

Estrogen deficiency impairs intestinal Ca absorption and induces bone loss, but its effects on the vitamin D-endocrine system are unclear. In the present study, calciotropic hormones levels, renal vitamin D metabolism, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-dependent intestinal calcium absorption, and bone properties in 3-mo-old sham-operated (sham) or ovariectomized (OVX) rats fed either a normal-Ca (NCD; 0.6% Ca, 0.65% P) or a low-Ca (LCD; 0.1% Ca, 0.65% P) diet for 2 wk were determined. LCD increased serum 1,25(OH)2D3 levels in both sham and OVX rats. Serum parathyroid hormone [PTH(1-84)] levels were highest in OVX rats fed LCD. Renal 25-hydroxyvitamin D1alpha-hydroxylase (1-OHase) protein expression was induced in both sham and OVX rats during LCD, while renal 1-OHase mRNA expression was highest in OVX rats fed LCD. Renal vitamin D receptor (VDR) and mRNA expressions in rats were induced by ovariectomy in rats fed NCD but suppressed by ovariectomy in rats fed LCD. The induction of intestinal calcium transporter-1 and calbindin-D9k mRNA expressions by LCD were not altered by ovariectomy. As expected, bone Ca content, cancellous bone mineral density, and bone strength index in proximal metaphysis of rat tibia were reduced by both ovariectomy and LCD (P<0.05) as analyzed by two-way ANOVA. Taken together, the data demonstrate that ovariectomy alters the responses of circulating PTH levels, renal 1-OHase mRNA expression, and renal VDR expression to LCD. These results suggest that estrogen is necessary for the full adaptive response to LCD mediated by both PTH and 1,25(OH)2D3.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1998

Effects of ovariectomy and hindlimb unloading on skeletal muscle.

Female rats (7-8 mo old, n = 40) were randomly placed into the intact control (Int) and ovariectomized control (Ovx) groups. Two weeks after ovariectomy, animals were further divided into intact 2-wk hindlimb unloaded (Int-HU) and ovariectomized hindlimb unloaded (Ovx-HU). We hypothesized that there would be greater hindlimb unloading-related atrophy in Ovx than in Int rats. In situ contractile tests were performed on soleus (Sol), plantaris (Plan), peroneus longus (Per), and extensor digitorum longus (EDL) muscles. Body weight and Sol mass were approximately 22% larger in Ovx than in Int group and approximately 18% smaller in both HU groups than in Int rats (Ovx x HU interaction, P < 0.05), and there was a similar trend in Plan muscle (P < 0.07). There were main effects (P < 0.05) for both ovariectomy (growth) and hindlimb unloading (atrophy) on gastrocnemius mass. Mass of the Per and EDL muscles was unaffected by either ovariectomy or hindlimb unloading. Time to peak twitch tension for EDL and one-half relaxation times for Sol, Plan, Per, and EDL muscles were faster (P < 0.05) in Ovx than in Int animals. The results suggest that 1) ovariectomy led to similar increases of approximately 20% in body weight and plantar flexor mass; 2) hindlimb unloading may have prevented ovariectomy-related muscle growth; 3) greater atrophy may have occurred in Sol and Plan of Ovx animals compared with controls; and 4) removal of ovarian hormonal influence decreased skeletal muscle contraction times.

Animals↗
PubMed1996

Effect of ovariectomy on glomerular injury in hypercholesterolemic female Imai rats.

To clarify the pathogenesis of focal and segmental glomerulosclerosis, we investigated the effect of ovariectomy in hypercholesterolemic female Imai rats. At 5 weeks of age, control female (group 1) and control male rats (group 3) were sham-operated, female rats (group 2) were ovariectomized and male rats (group 4) were castrated. Body weight, blood pressure, urinary protein and serum constituents were checked every 2 months from 2 through 12 months of age. All groups were studied morphologically at 6 months of age and further female groups (1 and 2) studied at 12 months. Both control female and control male rats developed marked proteinuria, to a significantly greater extent in the male rats. Castration reduced proteinuria, while ovariectomy did not influence it and there were no significant differences in proteinuria among the control females, the ovariectomized females and the castrated males. Control male rats had significantly lower serum albumin levels, higher cholesterol levels and a significantly greater impairment of renal function in blood urea nitrogen (BUN) levels than did the control female rats at 6 months. Castration significantly increased serum albumin levels and lowered BUN levels, while ovariectomy did not basically influence these values in the female rats. The glomerulosclerosis index at 6 months of age was significantly higher in the control males than in the control females. Castration attenuated glomerular injury, while ovariectomy aggravated glomerular injury to the same levels as found in the castrated males. This aggravating effect of ovariectomy observed at 6 months, however, disappeared at 12 months. These results suggested that sex-related factors regulated by the ovaries may play an inhibitory role in the development of glomerulosclerosis before 6 months of age, but not thereafter, in hypercholesterolemic female Imai rats.

Animals↗
PubMed1996

Ovariectomy attenuates proteinuria and glomerular injury in unilaterally nephrectomized female Sprague-Dawley rats.

To determine the contribution of the ovary to the development of glomerulo-sclerosis, we investigated the effect of ovariectomy on glomerulosclerosis, using the unilaterally nephrectomized (Nx) female Sprague-Dawley rat. At 6 weeks of age, groups 2 and 3 underwent unilateral right nephrectomy and group 3 was simultaneously ovariectomized, while group 1 underwent a sham operation. Body weight, blood pressure, urinary protein, serum albumin, cholesterol, blood urea nitrogen and serum creatinine were checked every 2 months from 2 to 12 months after right nephrectomy. Control group 1, the Nx group 2 and the ovariectomized (Nx + ovariectomized) group 3 were studied morphologically at 6 and 12 months after nephrectomy. Body weight significantly increased in ovariectomized rats as compared with control and Nx rats. Nx rats became proteinuric with age. Ovariectomy significantly reduced proteinuria to the same levels in the controls. The glomerulosclerosis index was significantly higher in Nx rats than in either controls or ovariectomized rats. Ovariectomy attenuated glomerular injury in Nx rats, though not to the same levels in the control rats. Three groups showed no significant differences in either blood pressure or plasma somatomedin C. Growth hormone (GH) was significantly decreased by ovariectomy. The severity of glomerular injury and the glomerular tuft volume correlated with GH levels. Our results suggested that a decrease in plasma GH may contribute to the attenuating effect of ovariectomy on the development of glomerular injury in aging unilaterally Nx female Sprague-Dawley rats.

Animals↗