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Effects of ovariectomy on mechanical properties and collagen content in rabbit lower urinary tract smooth muscle.

Fourteen female rabbits underwent ovariectomy or were sham-operated six weeks before investigation. Detrusor and urethral strips (longitudinal and circular urethral muscle fibers were studied separately) were prepared and length-tension relations studied in organ baths experiments. In addition, the specimens were examined for collagen content. Maximal active tension in the detrusor, longitudinal and circular urethral preparations, determined as the response to K+ (124mM), was reached when the length of the strips was 178 +/- 8% (n = 7), 153 +/- 9% (n = 5), and 127 +/- 5% (n = 7) of the resting length, respectively. Ovariectomy did not alter the length for development of maximal active tension. In detrusor strips, ovariectomy caused a significant increase in maximal active tension from 39 +/- 7 mN (sham-operated rabbits) to 79 +/- 11 mN (p < 0.01), despite an unchanged relative amount of smooth muscle. The maximal active tension produced in the urethra was lower (15-25 mN) than in the detrusor, and not significantly affected by ovariectomy. Approximately 40% of the dry defatted tissue weight of the detrusor consisted of collagen, whereas corresponding value in the urethra was 50-60%. Ovariectomy had no effect on tissue collagen concentrations. In conclusion, ovariectomy for six weeks did not affect the passive mechanical properties or the collagen concentration in rabbit lower urinary tract smooth muscle, but increased the responsiveness of the detrusor muscle to K+ (124 mM).

Animals↗

Ovariectomy in mice decreases lipid metabolism-related gene expression in adipose tissue and skeletal muscle with increased body fat.

Postmenopausal women as well as rodents after ovariectomy, which results in a lack of estrogen, can become obese. Ovariectomy-induced obesity in mice is associated with a decrease in oxygen consumption, indicating repressed energy expenditure. In this study, to elucidate the mechanism of weight gain after ovariectomy, we examined the expression patterns of genes related to energy expenditure and lipid metabolism, in mouse tissues including adipose tissue and skeletal muscle. In adipose tissue and skeletal muscle, at 2-4 wk after ovariectomy, levels of nuclear receptors and cofactors involved in energy expenditure such as ERR1, PPARalpha and PPARdelta, and PGC1alpha and PGC1beta were lower than in control mice. mRNA levels of their targets, medium-chain acyl coenzyme A dehydrogenase and acetyl CoA oxidase, enzymes for fatty acid beta-oxidation, were lower. In addition, the expression of PPARgamma and SREBP1, transcription factors important for lipogenesis, was decreased, as well as that of acetyl CoA carboxylase and fatty acid synthase, enzymes for fatty acid synthesis, and diacyl glycerol acetyl transferase 1 and 2, enzymes for triglyceride synthesis. These changes in gene expression are consistent with the obese phenotype in mice after ovariectomy. Thus a decrease in the expression of energy expenditure-related genes in adipose tissue and skeletal muscle could, in part, be responsible for obesity after ovariectomy.

Acetyl-CoA Carboxylase↗

The effect of simulated birth trauma and/or ovariectomy on rodent continence mechanism. Part I: functional and structural change.

PURPOSE: We examined the changes in the lower urinary tract after delivery, intravaginal ballooning and/or ovariectomy. MATERIALS AND METHODS: The study included 10 virgin and 48 primiparous pregnant rats. Cystometry and the stress/sneeze test were performed in virgin and postpartum rats shortly after delivery and at 8 weeks before sacrifice. Half of the delivered animals underwent intravaginal balloon dilation. Four weeks later half in each group underwent ovariectomy. The rats were subdivided into group 1--delivery, group 2--delivery plus balloon inflation, group 3--delivery plus ovariectomy and group 4--delivery plus balloon inflation plus ovariectomy. Tissues from the bladder, bladder neck, urethra and levator were collected, analyzed by electron microscopy, and immunostained for caveolin-1, caveolin-3 and neuronal nitric oxide synthase. RESULTS: Higher bladder capacity was detected in postpartum than in virgin rats. Urine leakage on stress/sneeze testing increased significantly in groups 2 and 4. Electron microscopy revealed a significant decrease in sarcolemma caveolae in the smooth muscle of the bladder and urethra in groups 2 to 4. In the bladder neck in group 3 caveolae were increased in smooth muscle. In groups 2 to 4 in the smooth muscle of the bladder and urethra caveolin-1 was significantly decreased. Caveolin-3 and neuronal nitric oxide synthase in striated muscle also significantly decreased in groups 2 to 4. CONCLUSIONS: These findings suggest that birth trauma simulated by ballooning and ovariectomy may contribute to stress urinary incontinence. The alteration in smooth muscle caveolae as well as the membrane protein caveolin may have a role in functional alterations caused by birth trauma and ovariectomy.

Animals↗

[Effects of nourishing shen-yin recipe and warming recuperating shen-yang recipe on interleukin-1 and interleukin-6 activity in ovariectomy induced osteoporosis rats].

OBJECTIVE: To compare the effects of the recipes for nourishing Shen-yin (NSY) and for warming recuperating Shen-yang (WRSY) on the activity of interleukin-1 (IL-1) and interleukin-6 (IL-6) in ovariectomy-induced osteoporosis rats. METHODS: Fifty-five female rats were randomly divided into five groups: the control, the sham operation, the ovariectomy, the ovariectomy plus NSY and the ovariectomy plus WRSY group. The medication was starting from one week after operation and lasted continuously for 3 months. The proximal tibia of rats were analyzed with bone histomorphometry, the activity of IL-1 was detected with mouse thymocyte assay and the activity of IL-6 was detected with IL-6 dependence cell proliferation assay. RESULTS: Three months after ovariectomy, the percentage of trabeculae bone volume (TBV%) of tibia in rats was markedly reduced, but the percentage of trabeculae absorption surface (TRS%) and trabeculae formation surface (TFS%) significantly increased, and the activity of IL-1 and IL-6 increased obviously. These abnormal changes could be reversed to different degree by NSY or WRSY, but the effect of the latter was superior to that of the former. CONCLUSION: The inhibitory effect of WRSY on IL-1 and IL-6 activity was significantly better than that of NSY, which is one of the mechanisms of its superiority in preventing osteoporosis induced by ovariectomy in rats.

Animals↗

Involvement of Fas in regression of vaginal epithelia after ovariectomy and during an estrous cycle.

Fas, also called APO-1, belongs to the tumor necrosis factor/nerve growth factor receptor family and transmits an apoptotic signal within the cell by binding to the Fas ligand. Fas has been implicated in the activation-induced suicide of T cells and cytotoxic T cell activity in the immune system. Non-immune cells such as those in liver, lung and ovary also express Fas, but its role in these cells remains unclear. Ovariectomy has been used to study homeostasis of female reproductive organs, which is regulated by sex hormones. Here we analyzed Fas function in the ovariectomy-induced regression of mouse vaginal epithelial cells. Fas expression was detected in vagina and was elevated after ovariectomy. Fas-deficient lpr and lpr(cg) mice did not exhibit ovariectomy-induced regression of vaginal epithelia, whereas uterine regression induced by ovariectomy was not affected in these mice. The vaginas of lpr and lpr(cg) mice were in a persistent estrous stage with cornification of vaginal epithelia, as judged from the cell types in the vaginal fluid. Thus, Fas appears to be involved directly in the regression of vaginal epithelia induced by ovariectomy and during the estrous cycle, suggesting that the physiological role of this receptor extends beyond that exerted on immune cells. This is the first evidence of a role for Fas inducing physiological apoptosis in non-immune cells.

Animals↗

Effects of ovariectomy on clock-timed daily gonadotropin rhythms in prepubertal golden hamsters.

Daily rhythms of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are measurable in the serum of prepubertal female golden hamsters by 17 days after birth. These rhythms, which are characterized by peak levels at 1700 h, persist until they are replaced by a 4-day rhythm as ovulatory cycles begin, approximately 3 wk later. We have tested the proposition that the ovaries are required for the onset and maintenance of clock-timed gonadotropin release by removing the ovaries and measuring the levels of LH and FSH in prepubertal hamsters. Ovariectomy was performed both before and after the onset of the rhythm and the effect of removal was determined by subsequent collection of blood samples during the mid- to late-prepubertal period. Ovariectomy on 7, 10 or 13 days after birth results in tonic levels of LH and FSH in blood samples collected at 1400, 1700 and 2000 h on Days 17 through 29. Sham-operated or intact controls had significantly elevated levels of these hormones at 1700 h. Ovariectomy on Day 21 and killing on Day 25 at the same times of day abolished the rhythm of serum LH measured in sham-ovariectomized controls. Ovariectomy on Day 21 and killing on Days 26, 28 or 30 at hourly intervals resulted in variable but nonrhythmic patterns of circulating LH. Thus, ovariectomy before the initiation of clock-timed gonadotropin release prevented its initiation; ovariectomy after its initiation abolished the rhythm. These results show that the ovary provides an essential "message" to the brain-pituitary axis for the initiation and maintenance of clock-timed gonadotropin release in prepubertal females.

Animals↗

Effect of ovariectomy on hormone receptors and growth of N-nitrosomethylurea-induced mammary tumors in the rat.

Estrogen receptor(s) (ER), progesterone receptor(s) (PGR), androgen receptor(s) (ANR), and prolactin receptor(s) (PRLR) were measured in N-nitrosomethylurea-induced mammary tumors in intact female Sprague-Dawley rats and in rats 9 days after ovariectomy. Following ovariectomy, 12 of 15 tumors regressed to 47.7 +/- 5.5% of the original size (hormone-dependent tumors), while the remaining three had arrest of growth reaching 88.8 +/- 7.3% of their original sizes. Cytosol ER level was 50.3 +/- 6.6 fmol/mg protein in tumors of intact rats and was significantly lower (25.6 +/- 8.3 fmol/mg, p < 0.025) in the ovariectomized group. PGR was abundantly present in ten of 13 tumors of intact rats (mean, 144.5 +/- 46.8) but was undetectable in five of six hormone-dependent tumors after ovariectomy (p < 0.01). ANR ws detectable at low levels in only four of 13 tumors of intact rats but in none of six hormone-dependent tumors after ovariectomy. PRLR was not significantly different in tumors of intact and ovariectomized rats (20.6 +/- 2.4 and 15.6 +/- 1.8 fmol/mg, respectively). In three tumors that had arrest of growth after ovariectomy, the levels of ER, PGR, ANR, and PRLR were not significantly different from those of the hormone-dependent tumors. We conclude that the majority of N-nitrosomethylurea-induced rat mammary tumors are hormone dependent. ER, PGR, and PRLR were abundantly present in the majority of these tumors, while ANR was present in only four of 13 tumors. The levels of ER and PGR were significantly lower following ovariectomy, while PRLR was not significantly changed.

Animals↗

The effect of ovariectomy on excretion of urinary steroids and tumor growth in rats bearing 7,12-dimethylbenz[a]anthracene-induced mammary cancer.

The relation between the excretion of urinary steroids and the therapeutic effect of ovariectomy on tumors was investigated in female Sprague-Dawley rats bearing 7,12-dimethylbenz[a]anthracene-induced mammary cancer. Ovariectomy significantly reduced the excretion of urinary androgen, 11-deoxy-17-oxosteroid (11-DOOS), but hardly affected that of urinary corticosteroid, 17-deoxy-corticosteroid (17-DOCS). The responsiveness of tumors to ovariectomy was positively correlated with both pre-operative 11-DOOS and pre-operative ratio of 11-DOOS to 17-DOCS, and negatively correlated with pre-operative 17-DOCS. The extent of tumor regression after ovariectomy was associated with the decrease of urinary androgen. A similar correlation was observed between the decrease in the ratio 11-DOOS/17-DOCS and tumor suppression during cyclophosphamide treatment (medical ovariectomy). These results indicated that the tumor response to ovariectomy was related to a shift of the endogenous hormone balance from a relative dominance of androgen to relative dominance of corticosteroid. The significance of the hormonal findings is discussed in the light of the steroid metabolism in human breast cancer.

9,10-Dimethyl-1,2-benzanthracene↗

Effect of ovariectomy on bone response to in vivo external loading.

This study was undertaken to find whether the bone response to increased external loading (EL) of the tibia in rats is affected by estrogen depletion. Female Sprague-Dawley rats 6 months were randomly assigned to four groups of 10 each: sham ovariectomy without loading (Shm-XL), ovariectomy without loading (OVX-XL), sham ovariectomy with external loading (Shm-EL), and ovariectomy with external loading (OVX-EL). In vivo external loading by a four-point bending device was initiated 4 weeks after surgery. The right lower leg of each EL rat was loaded at 31.4 +/- 0.2 N for 36 cycles at 2 Hz every other day for 21 days (11 loading days). Mean in vivo induced strain was 1305 microstrain (mu epsilon) for Shm-EL rats and 1280 mu epsilon for OVX-EL rats. With external loading of the tibia, periosteal bone formation rose equally in Shm and OVX rats. Woven bone was present around the tibia or fibula in 60% of the loaded rats and none of the control rats. No loading response occurred either at the endocortical surface or in the cancellous bone of the proximal tibial metaphysis. After OVX, cancellous bone area in the proximal metaphysis declined and formation surface rose compared to Shm rats. Although periosteal and endocortical bone formation rose after OVX, no cortical bone loss occurred. We conclude that ovariectomy and attendant loss of endogenous estrogen do not change the cortical bone response to an external load of about 1300 mu epsilon in rats. However, these results may not predict the cortical bone response to loading in animals with Haversian remodeling that display estrogen-related loss of cortical bone.

Analysis of Variance↗

Ovariectomy-induced bone loss occurs independently of B cells.

Estrogen withdrawal is associated with a significant expansion in B cell precursor and mature B cell populations. However, despite significant circumstantial evidence the role of B lineage cells in ovariectomy-induced bone loss in vivo is unclear. In vitro studies have demonstrated that mature B cells have the potential to both positively and negatively impact osteoclastogenesis by virtue of their capacity to secrete pro-osteoclastogenic cytokines including receptor activator of NFkappaB ligand (RANKL), as well as anti-osteoclastogenic cytokines such as osteoprotegerin (OPG) and transforming growth factor beta (TGFbeta). Although several studies have suggested that expansion of the B lineage following ovariectomy may play a key role in the etiology of ovariectomy-induced bone loss, in vivo studies to directly test this notion have yet to be conducted. In this study, we performed ovariectomy on microMT(-/-) mice which are specifically deficient in mature B cells. Analysis of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and micro-computed tomography (CT) demonstrate that mature B cell-deficient mice undergo an identical loss of bone mass relative to wild-type (WT) control mice. Our data demonstrate that mature B cells are not central mediators of ovariectomy-induced bone loss in vivo.

Absorptiometry, Photon↗

Influence of ovariectomy on bone metabolism in very old rats.

Twenty-five 30-month-old Lou rats fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi were divided into five groups. Four groups were surgically ovariectomized. From day 2 until day 29 after ovariectomy, they were S.C. injected either with 17 beta estradiol (E2; 10 micrograms/kg BW/48 hours) or progesterone (P; 140 micrograms/kg BW/48 hours), or 17 beta estradiol + progesterone (E2P) at the same doses, or solvent alone (OVX). The fifth group was sham operated (SH) and injected with solvent. Urine was collected in metabolic cages from day 24 to 29 after ovx, and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion (markers of bone resorption) was measured by HPLC. All animals were killed 30 days after ovariectomy. Serum was then collected for measurement of osteocalcin (OC), alkaline phosphatase (ALP), parathyroid hormone (PTH), and calcitonin (CT). At necropsy, the success of ovariectomy was checked by marked atrophy of the uterine horns. Left and right femur were harvested for densitometric and mineral analysis, respectively. Ovariectomy had no significant effect upon plasma calcium and PTH concentrations. E2 or E2P treatment significantly increased plasma PTH and calcitonin concentrations. Plasma OC concentrations and ALP were not different in any of the groups. In contrast, urinary excretion of PYD and DPD was higher in OVX than in SH rats. Bone mineral density (BMD) of the distal femur was decreased by OVX, but was not different in the E2P and SH groups. A similar pattern was observed for the mineral or Ca content of whole femur. Thus, OVX decreased BMD and bone mineral content (BMC) in very old female rats. Plasma OC concentration and ALP activity failed to demonstrate any significant effect of OVX, whereas PYD and DPD were elevated. These results suggest that bone resorption is increased in OVX rats, even when supplemented with E2 or P alone. However, no significant difference was observed between SH and OVX rats treated with supplementation of both E2 and P. Thus, in very old rats, a combination of E2 and P is much more effective than E2 or P alone to prevent bone loss following ovariectomy.

Aging↗

Ovariectomy combined with amyloid beta(1-42) impairs memory by decreasing acetylcholine release and alpha 7nAChR expression without induction of apoptosis in the hippocampus CA1 neurons of rats.

In this study, the effect of ovariectomy and amyloid Beta(1-42) (ABeta(1-42))on eight-armed radial maze performance, acetylcholine (ACh) release, Alpha7nACh receptor (Alpha7nAChr), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression, and apoptosis of CA1 neurons in the dorsal hippocampus were investigated in rat. The results showed that the dorsal hippocampus of sham rats contains 136.7 -/+ 16.7 to 160.4 -/+ 21.1 fmol/microl ACh, and respective 201 -/+ 22.9 and 416.6 -/+ 66.3 expression of mRNA for a7nAChR and GAPDH. Ovariectomy alone, after 4 weeks, did not impair memory, and neither induced apoptosis nor changed the basal ACh release. On the other hand, ABeta(1-42) (600 pmol/10 microl/body/day i.c.v. for 7 days) impaired memory, an effect characterized by increased error choices and reduced (50-59%) ACh release, but only with slight apoptosis. Moreover, ovariectomy combined with ABeta(1-42) induced memory impairment characterized by decreased numbers of correct choices and increased numbers of errors. This effect was accompanied by a decrease of the basal ACh level (67%), a7nAChR mRNA expression (52%) and a7nAChR/GAPDH ratio (44%) without induction of apoptosis in the dorsal hippocampus. The high K+-evoked ACh release was not altered in ovariectomized rats, but was decreased by ABeta(1-42) (43%) and ovariectomy + ABeta(1-42) (80%). These results suggest that ovariectomy-induced hormonal deprivation after 4 weeks, when accompanied by ABeta(1-42) accumulation in the dorsal hippocampus, could impair memory by decreasing ACh release and a7nAChR expression without inducing apoptosis in the CA1 field of the dorsal hippocampus.

Acetylcholine↗

Ovariectomy-induced changes in aged beagles: histomorphometry of rib cortical bone.

Bone loss associated with estrogen depletion is well documented in cancellous bone but less well characterized in cortical bone. The effects of ovariectomy on the aged beagle skeleton were studied by histomorphometric analysis of the cortical bone in sequential rib biopsies. Biopsies were taken from each ovariectomized or sham-operated dog at the time of surgery and at 1, 4, and 8.5 months after surgery. Just prior to each postoperative biopsy, tetracycline, calcein, and xylenol orange, respectively, were administered by a fluorochrome labeling procedure (2d-10d-2d) to provide markers of bone formation. Analysis of sequential rib biopsies provided a means to follow the ovariectomy response over time and to compare each animal against its own baseline. Though ovariectomy did not influence histomorphometric indices at 1 month after surgery, a transient increase in cortical bone formation occurred thereafter, with a sixfold increase over that of sham-operated dogs at 4 months (P < 0.001) and a return to near control levels at 8.5 months. Cortical porosity increased by the fourth month after ovariectomy and remained high at 8.5 months. These data demonstrate for the first time that rib cortical bone is a responsive site for the effects of ovariectomy in aged female dogs.

Aging↗

Ovariectomy enhances acetylcholinesterase activity but does not alter ganglioside content in cerebral cortex of female adult rats.

In the present work we investigated the effect of ovariectomy on acetylcholinesterase (AChE) activity and ganglioside content in cerebral cortex of female rats. We also studied the activity of butyrylcholinesterase (BuChE) in serum of these animals. Adult Wistar rats were divided into three groups: (1) naive females (control), (2) sham-operated females and (3) castrated females (ovariectomy). Thirty days after ovariectomy, rats were sacrificed by decapitation without anaesthesia. Blood was collected and the serum used for BuChE determination. Cerebral cortex was homogenized to determine AChE activity and extracted with chlorophorm:methanol for ganglioside evaluation. Results showed that rats subjected to ovariectomy presented a significant increase of AChE activity, but did not change the content and the profile of gangliosides in cerebral cortex when compared to sham or naive rats. BuChE activity was decreased in serum of rats ovariectomized. Our findings suggest that the alteration in the activity of brain AChE, as well as serum BuChE activity caused by ovariectomy may contribute to the impaired cognition and/or other neurological dysfunction found in post-menopausal women.

Acetylcholine↗

Debenzoylating and deacetylating activities of rat liver and mammary gland microsomes. Effect of ovariectomy.

This study compared the rates of N-deacylations of N-hydroxy-N-2-fluorenylbenzamide (N-OH-2-FBA) with those of its analogue, N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA), by the mammary gland (tumor target for both compounds) and the liver of female Sprague-Dawley rats and examined the effect of ovariectomy on these activities. N-Debenzoylation of N-OH-2-FBA was catalyzed by the mammary and liver microsomes of 50-day-old female rats at similar rates (approximately 24 nmol/min/mg). The activity of both tissues increased (up to 1.8 times) after ovariectomy at 42, 32 and, especially, 22 days of age. The rapid hydrolysis appeared to be unique for the benzoyl group since N-OH-2-FAA was deacylated only approximately 0.05 and 0.004 times as fast by the liver and mammary microsomes, respectively, and these low rates were unaffected by ovariectomy. Since such substrate specificity would be of significance in the metabolism of xenobiotics and drug design, esterase activity and its sensitivity to ovariectomy at 22 days of age were examined with several acetylated and benzoylated substrates in the liver and mammary microsomes and compared with those of male liver. Tissues of rats of both sexes had a greater capacity to hydrolyze carboxyl esters than amides. Expect for N-2-fluorenylacetamide (2-FAA) and o-nitrophenylacetate (o-NPA), all substrates were hydrolyzed by liver microsomes of the male up to 3.9 times faster than by those of the female. Microsomes of female liver hydrolyzed acetylated substrates 1.2 to 25 times faster than benzoylated analogues except for N-OH-2-FBA and benzamide. By contrast, mammary gland microsomes hydrolyzed benzoylated compounds 1.4 to 333 times faster except for 2-naphthyl benzoate. Respective rates of hydrolysis of o-NPA by microsomes of liver and mammary gland were 1.7 and 0.6 times those of p-NPA. After ovariectomy, deacylating activities increased (up to 1.6 times) except for those of 2-FAA and acetanilide. All deacylations were > 98% inhibited by 0.1 mM paraoxon, indicating catalysis by serine hydrolases. The results suggest involvement of multiple carboxylesterases and indicate that certain benzoylated xenobiotics may have a greater effect on the mammary gland than acetylated xenobiotics because of their greater vulnerability to hydrolysis by esterases of mammary gland.

2-Acetylaminofluorene↗

Effects of ovariectomy on thermogenesis in brown adipose tissue and liver in Syrian hamsters.

Weight gain in ovariectomized Syrian hamsters occurs without increased food intake, which suggests that metabolic efficiency may be enhanced through a reduction in energy expenditure. We examined the effect of ovariectomy on metabolic activity in brown adipose tissue and liver. Four groups of hamsters (n = 13, each) were killed 0, 2, 4, or 16 weeks following ovariectomy. Ovariectomized hamsters rapidly gained weight without overeating. Body weights stabilized after 8 weeks and remained 12-17% above sham-operated control weights for the duration of the experiment. Weight gain in the hamsters ovariectomized for 16 weeks was characterized by significant increases in retroperitoneal white adipose tissue weight and carcass lipid content. Similar trends were seen in 2-week and 4-week ovariectomized animals. There were no differences in interscapular brown adipose tissue weight, protein content, DNA content, or norepinephrine (NE) content among sham-operated and 2-, 4-, or 16-week ovariectomized hamsters, indicating that ovariectomy had no effect on brown adipose tissue growth. Similarly, there was no difference in either sympathetic nervous system activity (estimated by the rate of NE turnover) or mitochondrial GDP binding among the four groups of hamsters. In contrast, hepatic cytochrome P-450 activity was significantly reduced 2, 4, and 16 weeks after ovariectomy. These results suggest that reduced thermogenic activity in liver, but not in brown adipose tissue, could contribute to the weight gain in Syrian hamsters after ovariectomy.

Adipose Tissue, Brown↗

Comparative morphometric changes in rat cortical bone following ovariectomy and/or immobilization.

Gonadal hormone deficiency following ovariectomy and skeletal unloading by limb immobilization are useful models of osteopenia. The purpose of this study was to compare changes in cortical bone after ovariectomy (OVX) or immobilization (IMM) for 6 and 12 weeks. Comparisons were also made when rats were ovariectomized or immobilized for 6 weeks and then immobilized (OVX/IMM) and ovariectomized (IMM/OVX), respectively, for 6 more weeks. Tibias and femurs were collected and static and dynamic cortical bone indices were determined by morphometric methods. Femurs from animals OVX or IMM for 12 weeks were tested for bone stiffness by torsional testing. Six and 12 weeks after OVX, there were increases in the periosteal perimeter, cortical area, and periosteal bone formation indices, indicating that ovariectomy increased modeling-dependent bone gain on the periosteal envelope, relative to controls. Contrarily, 6 and 12 weeks after IMM, there were decreases, compared with controls, in periosteal perimeter, cortical bone area, and periosteal bone formation indices. This indicates that immobilization decreased modeling-dependent bone gain on the periosteal envelope. These differences in modeling between the animals that were OVX and IMM resulted in a smaller cortical width and minimum cortical width in the IMM compared with the OVX animals. There were significant decreases in cortical bone stiffness and minimum cortical width at the fracture site following mechanical testing in the animals IMM for 12 weeks. Both ovariectomy and immobilization increased endocortical resorption surface, endocortical perimeter and expansion of the marrow cavity. Because of suppressed periosteal bone formation with increased endocortical resorption, immobilization had a greater effect on bone loss and decreased bone stiffness than did ovariectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Uterine transcriptomes of bacteria-induced and ovariectomy-induced preterm labor in mice are characterized by differential expression of arachidonate metabolism genes.

OBJECTIVE: The purpose of this study was to identify changes in gene expression that are associated with preterm labor induced by either bacteria or ovariectomy. STUDY DESIGN: Pregnant mice (14.5 days of gestation) were allocated to: (1) intrauterine injection of heat-inactivated Escherichia coli; (2) media alone; (3) ovariectomy; or (4) sham operation. The uterine transcriptome was studied with photolithographic, very short oligonucleotide-based microarrays, and arachidonate metabolism genes were assayed with quantitative reverse transcriptase-polymerase chain reaction. Significance was determined by analysis of variance. RESULTS: Microarray-based gene expression changes in the arachidonate metabolism pathway are associated globally with bacteria-induced preterm labor (P < or = .0031) and ovariectomy-induced preterm labor (P < or = .00036). Quantitative real-time reverse transcriptase-polymerase chain reaction measurements demonstrated that bacteria-induced preterm labor substantially increased the expression of genes involved in prostaglandin synthesis. In contrast, ovariectomy-induced preterm labor increased the expression of genes involved in lipoxin, leukotriene, and hydroxyeicosatetraenoic acid synthesis. CONCLUSION: Bacteria-induced and ovariectomy-induced preterm labor each express a different balance of genes that are required for the synthesis of prostaglandins, lipoxins, leukotrienes, and hydroxyeicosatetraenoic acids.

Animals↗