Long-term Effects Of Ovariectomy Research Articles

Long-term effects of ovariectomy on the properties of bone in goats.

Large animal models of osteoporosis are essential for osteoporosis research. However, the time required to establish an accurate osteoporosis model is unknown. Therefore, the aim of the present study was to establish a large animal model of osteoporosis in goats. In total, 14 Chinese goats were divided into an ovariectomized (OVX, n=7) or sham-operated (SHAM, n=7) group. Vertebral bodies were used to measure the bone mineral density (BMD) prior to the ovariectomy and at 24 months after the ovariectomy. In addition, the BMD of the femoral neck, femoral diaphysis and tibial diaphysis were measured 24 months postoperatively. Bone samples from the vertebral body, femoral head and femoral neck were scanned by micro-computed tomography (CT) to visualize the trabecular and cortical microstructure. Furthermore, the vertebral body, femoral head, femoral neck and tibial diaphysis were analyzed for mechanical strength. The BMD of vertebral body of the OVX group decreased significantly (P<0.01) at 24 months after the ovariectomy when compared with the baseline measurements. Micro-CT scans of the vertebral body revealed that the bone volume fraction, trabecular number, trabecular thickness and the degree of anisotropy decreased by 37.1, 36.7, 10.5 and 16.5%, respectively (P<0.01) in the OVX group when compared with the SHAM group. Additionally, the specific bone surface and trabecular spacing significantly increased by 37.7 and 62%, respectively in the OVX group (P<0.001). Cortical bone porosity in the vertebral body and femoral neck was greater in the OVX group when compared with the SHAM group (P<0.05). In addition, mechanical testing revealed a statistically significant difference between the vertebral bodies of the OVX group and the SHAM group. In conclusion, the present study demonstrated that an ovariectomy was able to induce significant osteoporosis and deterioration of mechanical properties in the bones of goats.

The long-term effects of ovariectomy on bone metabolism in sheep

Osteoporosis and associated fractures are major public health concerns, and as such require appropriate large animal models to further our understanding of this disease. Although sheep appear to be an ideal model with which to study bone loss caused by estrogen depletion, limited data are available concerning the long-term effect of ovariectomy on bone in sheep. The goal of the present study was to observe the ovariectomy-induced changes in bone mass, structure, and metabolism in sheep over a period of 18 months. Six ewes were ovariectomized (OVX) and compared to an age-matched control group by analyzing bone mineral density, trabecular structure, biochemical markers of bone formation and resorption, and plasma estrogen levels. Bone loss (13%, P < 0.01) occurred during the first 4 months after surgery, then stabilized and returned to pre-OVX levels for the remainder of the study. Trabecular architecture was also altered and tended toward osteopenia with recovery to baseline values. Markers of bone formation and resorption were elevated up to 6 months postovariectomy, after which time levels returned to baseline values. Although estradiol measurements demonstrated a clear decline following surgical ovariectomy, levels returned to normal after 6 months. Therefore, the detrimental effect of ovariectomy on sheep bone metabolism seems to be reversible, with normal bone parameters being reestablished within 6 months after surgery. These data seem to indicate that the sheep is not an appropriate model for human postmenopausal osteoporosis.

Long-term effects of ovariectomy and estrogen replacement treatment on endothelial function in mature rats

Objectives: Estrogen replacement therapy (ERT) improves blood flow through various mechanisms including an augmented release of nitric oxide (NO). We report on the long-term effects of estrogen loss on vascular function and endothelial regulation. Methods: Male, female, ovariectomized and ovariectomized+ERT treated rats were used. Female rats were ovariectomized at 12 weeks of age and received ERT via subcutaneously implanted 90-day release pellets. Vasodilation to acetylcholine (ACh) was studied in tail artery segments; arterial blood was collected for measurements of 17-β-estradiol and stable metabolites of NO (nitrate/nitrite). Some arterial segments were harvested for TUNEL staining to determine endothelial apoptosis. Results: Ovariectomy caused a rapid loss of estradiol that was negated by ERT. Likewise, there was also a loss in plasma NO. Loss of ACh-mediated dilations were age-dependent and were significant in males and untreated ovariectomized rats, with the change being maximal after 12 weeks of ovariectomy. After 12 weeks post-ovariectomy, there were no time dependent changes in ACh sensitivity in either group. Dilations to ACh were maintained in females and age-matched ERT ovariectomized rats over time. TUNEL staining of the endothelium (at 6 months of age) revealed apoptotic changes with the rank order male>ovariectomized>female, or ERT treated ovariectomized female rats. Conclusions: In a rat model of surgical menopause, loss of endothelial function is maximal 12 weeks after ovariectomy. Apoptosis of endothelial cells is greatest in arteries from male rats. Our data suggests that early ERT treatment may be an important consideration for reducing endothelium-dependent vascular dysfunction.

Long-Term Effect of Ovariectomy and Simulated Birth Trauma on the Lower Urinary Tract of Female Rats

Long-Term Effect of Ovariectomy and Simulated Birth Trauma on the Lower Urinary Tract of Female Rats

The effects of long-term ovariectomy and estrogen replacement therapy on learning and memory in monkeys (Macaca fascicularis).

This study determined the effects of estrogen loss and replacement therapy on learning and memory function in monkeys (Macaca fascicularis). The ability to learn, remember, and perform reversals of object discriminations and the accuracy on a spatial delayed response task were found to be comparable in young adult surgically menopausal monkeys receiving estrogen or placebo treatment for 5 or 16 months. Learning and memory abilities were comparable with baseline values following 2, 12, or 24 months of ovariectomy in monkeys. Pre- and postoperative injections of scopolamine in a subset of monkeys revealed only subtle increases in sensitivity on the delayed response task following ovariectomy. These observations in surgically menopausal monkeys have some parallels with those made in surgically menopausal women and suggest that, in the absence of other confounding factors, certain aspects of learning and memory may not be influenced by estrogen in primates.

The effects of long-term ovariectomy and estrogen replacement therapy on learning and memory in monkeys (Macaca fascicularis).

This study determined the effects of estrogen loss and replacement therapy on learning and memory function in monkeys (Macaca fascicularis). The ability to learn, remember, and perform reversals of object discriminations and the accuracy on a spatial delayed response task were found to be comparable in young adult surgically menopausal monkeys receiving estrogen or placebo treatment for 5 or 16 months. Learning and memory abilities were comparable with baseline values following 2, 12, or 24 months of ovariectomy in monkeys. Pre- and postoperative injections of scopolamine in a subset of monkeys revealed only subtle increases in sensitivity on the delayed response task following ovariectomy. These observations in surgically menopausal monkeys have some parallels with those made in surgically menopausal women and suggest that, in the absence of other confounding factors, certain aspects of learning and memory may not be influenced by estrogen in primates.

Ovarian modulation of the oestradiol-induced LH surge in prepubertal and sexually mature gilts.

The role of ovarian secretions in modulating positive oestrogen feedback on LH release in late prepubertal and sexually mature gilts was studied. Gilts were either ovariectomized (OVX) at 230 days of age (sexually mature, OVX 230, control), ovariectomized at 160 days of age (pre-pubertal, OVX 160) or ovariectomized at 160 days of age and given either low, high or very high oestradiol substitution therapy (two or three Silastic implants, 5 or 8 cm in length) from 160 days to 230 days (OVX 160 + 2E5, OVX 160 + 2E8 and OVX 160 + 3E8, respectively). The LH surge responses to three i.m. injections of oestradiol benzoate given at intervals of 12 h (in total 10 micrograms oestradiol benzoate kg-1 bodyweight) were compared at 260 days. An additional group of sexually mature gilts was ovariectomized at 260 days (OVX 260) and challenged with oestradiol benzoate at 360 days. LH surges with peak LH concentrations below pretreatment values (resembling LH responses to oestradiol benzoate in immature gilts) were classified as immature, and those with peak LH concentrations above pretreatment values as mature. LH concentrations before treatment with oestradiol benzoate were reduced (P < 0.05) in OVX 160 + 2E8 and OVX 160 + 3E8 gilts compared with OVX 230 (control). When compared with the control group, the time to LH surge peak was longer in OVX 260 gilts, LH peak amplitude was reduced in the OVX 160 group and the area under the curve of the LH surge (ng LH ml-1 plasma (48 h)-1) was less in all other groups (P < 0.05). Classification of LH surges by mature:immature criteria indicated a high mature:immature ratio in OVX 230 gilts (6/1) and a low ratio in OVX 160 (1/7) and OVX 260 (1/6) gilts. The long-term effect of ovariectomy was partially overcome in the OVX 160 + 2E5 group (mature:immature = 3/3). However, previous exposure to supraphysiological concentrations of oestradiol (as in groups OVX 160 + 2E8 and OVX 160 + 3E8) resulted in a high percentage of animals (66% and 100%, respectively) that did not respond to the oestradiol benzoate challenge with an LH surge. Immediately before oestradiol benzoate administration (30 days after removal of implants) plasma oestradiol concentrations in these two groups were still high (P < 0.05) compared with all other groups. GnRH-induced (0.2 microgram kg-1 bodyweight) LH secretion, evaluated 10 days after treatment with oestradiol benzoate, was depressed (P < 0.05) in OVX 160 + 3E8 gilts, but not affected by age at ovariectomy. We suggest that continuous ovarian secretion is necessary for the final maturation of the LH surge mechanism in late prepubertal gilts and also for maintaining the full functionality of this mechanism in sexually mature gilts. The range over which ovarian oestrogens tune the final maturation of this process appears to be rather narrow; however, other ovarian factors may contribute to the final maturation. Furthermore, continued exposure to supraphysiological concentrations of oestradiol was found to be detrimental to the development of the LH surge mechanism.

Long-term effects of ovariectomy on the mechanical properties and chemical composition of rat bone

One hundred Sprague-Dawley rats were ovariectomized (OVX) or sham-operated (Sham) at the age of 12 weeks. Eight or six animals from each group were sacrificed at the following time points: 0, 2, 4, 8, 16, 28, and 40 weeks. Mechanical testing of the bones showed that the maximal load of the femoral neck remained at the baseline level in OVX rats but clearly increased in Sham animals. However, after 28 weeks (at the age of 40 weeks) of ovariectomy, the femoral neck strength in Sham animals started to decrease, reaching the OVX level at the age of 1 year. The gain of torsional strength of the humerus was first slowed down after ovariectomy, but 16 weeks after operation this difference between the OVX and Sham animals disappeared. In OVX rats incorporation of 45Ca 2+ into the tibia and the number of osteoclasts on the trabecular bone surfaces were increased at 4–16 weeks and at 2–28 weeks, respectively, but they returned later to the levels observed in Sham animals. This indicates that the OVX-induced increase in bone turnover is transient. The trabecular bone volume at the distal femur decreased and the area of the marrow cavity in the distal third of the femur increased after OVX and did not show any recovery. Analysis of the inorganic composition of bone by energy-dispersion spectrometry showed that the percentage of magnesium was transiently decreased after OVX in both trabecular and cortical bone. Despite the OVX-induced loss of trabecular bone, increasing body weight or some metabolic changes may induce structural changes which may be responsible for maintaining the mechanical force of the femoral neck in aging OVX rats.

Long-Term Effects of Ovariectomy on Abdominal Fat Body and Body Masses in the Frog Rana tigrina during the Recrudescent Phase

Long-Term Effects of Ovariectomy on Abdominal Fat Body and Body Masses in the Frog Rana tigrina during the Recrudescent Phase

Prolactin binding sites in rat brain and liver: effects of long-term ovariectomy and ovarian steroids

The effects of long-term ovariectomy on the levels of brain and liver lactogenic binding sites as well as plasma and liver prolactin (PRL) have been investigated in sham-operated and ovariectomized rats receiving either 17β estradiol (OVX-E), progesterone (OVX-P), or vehicle (OVX-V). The levels of lactogenic binding sites in the parietal and piriform cortices, amygdala, thalamus, hypothalamus, as well as in the liver were significantly decreased after long-term ovariectomy. Moreover, the levels of plasma and liver PRL were also significantly decreased. Exogenous estradiol and progesterone replacement restored the levels of lactogenic binding sites in the parietal cortex and hypothalamus as well as in the liver. However, plasma and liver PRL levels were significantly increased by estradiol but only restored by progesterone. These results suggest that ovarian steroids influence the levels of lactogenic binding sites and prolactin.

Effects of long-term ovariectomy and ovarian steroids on somatogenic binding sites in rat brain and liver

The effects of long-term ovariectomy and replacement with ovarian steroids on the levels of brain and liver somatogenic binding sites as well as plasma and liver growth hormone (GH) were studied in sham-operated (Sham) and ovariectomized female rats receiving either, 17β-estradiol (OVX-E), progesterone (OVX-P), or vehicle (OVX). Long-term ovariectomy decreased the levels of somatogenic binding sites in the choroid plexus and liver as well as GH in plasma and liver. The levels of these sites in the choroid plexus were partially restored only by estradiol replacement. Moreover, exogenous estradiol but not progesterone restored the levels of plasma and liver GH as well as liver somatogenic binding sites. Our results suggest that estrogens regulate the levels of somatogenic binding sites in the liver and choroid plexus.

Heterogeneous decrease of bone mineral density in the vertebral column of ovariectomized rats

The long-term effect of ovariectomy on the loss of bone mineral density (BMD) was evaluated in rats with and without estrogen treatment; BMD was studied in the lumbar and caudal vertebrae, measured by DXA, to find how the losses of BMD occur in the axial skeleton. Seventy female Wistar rats of 3 months of age were divided into four groups as follows: group 1: control animals; group 2: ovariectomized animals; group 3: ovariectomized animals undergoing treatment with estrogen (0.25 mg/kg per week of 17-beta estradiol); group 4: ovariectomized rats undergoing estrogen treatment only during the last 3 months of the experimental period. No significant differences were found among the groups in regard to the BMD values of the caudal vertebrae at either 3 or 6 months. Likewise, in the lumbar vertebrae there were no significant differences among the groups after 3 months. However, at 6 months, a decrease in the BMDs of the ovariectomized animals with respect to the remaining groups was found: 226 +/- 11 mg/cm2 in the ovariectomized group; 262 +/- 14 mg/cm2 in the controls; 255 +/- 4 mg/cm2 in the rats receiving estrogen treatment for 6 months; and 259 +/- 5 mg/cm2 in the animals receiving estrogen for 3 months. The study also reveals the absence of differences in the bone mineral density between the ovariectomized and control rats when the former received estrogen treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The long-term effect of ovariectomy on the quality and quantity of cancellous bone in young macaques

The effect of ovariectomy on the quality and quantity of cancellous bone using the young cynomolgus monkey was evaluated after a 2-year period. The bodies of the second lumbar vertebrae were analyzed for changes in bone mineral quality using density fractionation, chemical analysis, and X-ray diffraction techniques. Changes in bone tissue quality and quantity were evaluated using bone histomorphometry and image analysis. The experimental group ( n=14) was made surgically menopausal (bilaterally ovariectomized), compared with intact controls ( n=16), and then sacrificed after a 2-year period. There was a non-significant shift in the mineralization profile towards less dense bone in the ovariectomized (OVX) vertebrae compared with controls. Physical characteristics of the bone mineral in terms of crystal size or strain were unaffected by OVX. There was a parallel increase in mineral content with fractions of increasing density, however there was no difference in mineral content or the Ca/P ratio in each fraction between treatment groups. Histomorphometric analysis for structural parameters demonstrated no difference in bone volume between control and OVX groups. There was no significant change in trabecular width in the OVX vertebrae compared with controls. There was a significant increase in both osteoid volume and osteoid surface in the OVX vertebrae ( P<0.001). Trabecular architecture as measured by image analysis was unchanged. There was a significant increase in eroded surface in the OVX vertebrae ( P<0.03) compared with the controls. In conclusion, young, ovariectomized female cynomolgus macaques do not appear to be a useful animal model for the study of postmenopausal bone loss, however they may be a useful model to evaluate skeletal pathology which might be observed after surgical ovariectomy in young human females.

The longterm effect of ovariectomy on the quality and quantity of cortical bone in the young cynomolgus monkey: A comparison of density fractionation and histomorphometric techniques

The longterm effect of ovariectomy on the quality and quantity of cortical bone in the young cynomolgus monkey: A comparison of density fractionation and histomorphometric techniques

Long-term effects of ovariectomy on pituitary-adrenal axis and specific antibody response in rats

The effects of ovariectomy on morphologically demonstrable characteristics of lymphoid tissue, pituitary, and adrenal glands as well as on plasma ACTH and corticosterone levels and humoral immunity of female Lewis rats were investigated. The present study establishes ovaries as potential regulatory organs upon thymus, pituitary, and adrenal glands in female Lewis rats. In addition to the effects on these important lymphoid organs and endocrine glands, ovariectomy influenced the time course of serum IgM antibody titres against fluorescein isothiocyanate (FITC), but had only moderate effects upon serum IgG antibody titres. In conclusion, the present results suggest that ovariectomy modifies morphological characteristics of the thymus and pituitary-adrenal axis. Furthermore, circulating corticosterone seems to play an important role in regulating antibody formation in intact compared to ovariectomized female Lewis rats, while the influence of thymic mass is far from clear.

Influence of Ovariectomy and Regional Fat Distribution on the Membranous Transducing System Controlling Lipolysis in Rat Fat Cells*

The mechanism by which sex steroid hormones modulate the lipolytic process in fat cells is still not completely understood, particularly at the level of the membrane. As estrogens seem to have regional influence on adipose tissue, we have compared the effects of long term ovariectomy (3 weeks) on the membranous transducing system controlling lipolysis in two rat fat deposits, the femoral sc and the parametrial adipose tissue. These experiments demonstrate the following. 1) Compared to parametrial adipocytes, sc adipocytes have a reduced cAMP production and a decreased beta-adrenoceptor number associated with a reduced lipolytic activity. 2) In parametrial adipocytes, ovariectomy induces a decrease in cAMP production and in both the beta-agonist-stimulated response and the catalytic activity of adenylate cyclase in association with a decreased lipolysis. In contrast, these parameters are unaltered by ovariectomy in sc adipocytes. This study, which reveals site-related differences in the sensitivity of the fat cell adenylate cyclase system to ovarian status, suggests that these differences may explain some of the sex-related regional specificities of adipose tissue metabolism and distribution.

Long-term effects of ovariectomy and aging on the rat skeleton

The long-term skeletal effects of ovariectomy and aging were studied in female Sprague-Dawley rats sacrificed at 270, 370, and 540 days after bilateral ovariectomy (OVX) or sham surgery at 90 days of age. The proximal tibia was processed undecalcified for quantitative bone histomorphometry. For continuity, data from these late time points were combined with previously published data from earlier time points (0-180 days). A biphasic pattern of cancellous bone loss was detected in the proximal tibial metaphysis of OVX rats. An initial, rapid phase of bone loss out to 100 days was followed by an intermediate period of relative stabilization of cancellous bone volume at the markedly osteopenic level of 5-7%. After 270 days, a slow phase of bone loss occurred during which cancellous bone volume declined to 1-2%. Both the initial, rapid phase and the late, slow phase of bone loss in OVX rats were associated with increased bone turnover. In control rats, cancellous bone volume remained constant at 25-30% out to 270 days (12 months of age), then decreased to approximately 10% by 540 days (21 months of age). This age-related bone loss was also associated with increased bone turnover. It is interesting to note that the proximal tibial growth plates were closed in approximately a quarter of the control rats by 15-21 months of age. Our data indicate that a slow rate of bone loss and increased bone turnover persist in OVX rats during the later stages of estrogen deficiency. Therefore, the development of osteopenia is coincident with increased bone turnover in OVX rats as well as in aged, control rats.

The Decidual Cell Response in Aging C57BL/6J Mice is Potentiated by Long-term Ovariectomy and Chronic Food Restriction

The effects of long-term ovariectomy (LOVX) and chronic food restriction on the decidual cell response were examined in aging mice. At 2 mos of age, mice were either ovariectomized, started on a regimen of food restriction (70% of ad lib intake), or left untreated. At 10 mos, the decidual cell response (DCR) was induced in all groups and measured by uterine weight gain, alkaline phosphatase activity, and DNA content. The DCR was also examined in young (4.5 mos) mice. LOVX and, to a lesser extent, food restriction (FR) potentiated the DCR, as indicated by 20-75% greater alkaline phosphatase activity and uterine weight relative to age-matched controls. In contrast to previous reports, however, there was no age-related reduction of the DCR. These results show that both LOVX and FR can enhance uterine function in middle-aged mice and indicate that, under some experimental conditions, there is no age-related impairment in the DCR.

Age-Related Alterations in Pulsatile Luteinizing Hormone Release: Effects of Long-Term Ovariectomy, Repeated Pregnancies and Naloxone1

Aging of the female reproductive system may be regulated by changes at the hypothalamic, pituitary, and ovarian levels. Long-term ovariectomy (LT-OVX) and/or multiple pregnancies delay age-related deterioration of several parameters of reproductive potential in rodents. We tested whether long-term suppression of cyclic ovarian hormone release that is normally associated with the 4- to 5-day estrous cycle decelerates age-related decreases in the frequency of luteinizing hormone (LH) pulses to assess whether hormonal milieu influences the rate of aging of the pulse generator. We determined the percentage of rats exhibiting pulsatile LH secretion, mean LH levels, and amplitude and frequency of LH pulses in seven groups of ovariectomized (OVX) rats. Young (3-4 mo), middle-aged (8-10 mo), and old (18-22 mo) virgin rats, ovariectomized 4 wk (4WK-OVX) prior to experimentation, were used to determine the effect of age. The effect of long-term ovarian hormone deprivation was tested by ovariectomizing rats at 2-3 mo of age and using them when they were middle-aged (8-10 months) or old (18-22 mo). The effect of deprivation of cyclic increases in ovarian hormones associated with repeated estrous cycles was tested by using retired breeder (RB) rats that had been ovariectomized 4 wk prior to experimentation. Each rat was implanted with a right atrial cannula and bled the next day at 10-min intervals for 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)

The estrogen receptor in the rat kidney. Ontogeny, properties and effects of gonadectomy on its concentration

Estrogens have been suggested as modulators of the conversion of 25-hydroxyvitamin D 3 to dihydroxylated compounds in the kidney. In order to further explore this hypothesis the estrogen-binding components in the kidney were studied in adult and immature rats. The basal receptor levels in adult animals were 9.6 fmol/mg protein (female) and 21.9 (male). The receptor-ligand complex had a K d of 0.7 nM. Furthermore, the kidney receptor displayed similar characteristics as those of the cytosol liver estrogen receptor in terms of sedimentation properties on sucrose gradients, isoelectric focusing and ligand binding specificity. The ontogeny of cytosol high affinity estrogen binding sites was elucidated in female and male animals. Detectable levels of receptors (5 fmol/mg protein) were found during the first postnatal week in both sexes. During days 22–25 receptors reached maximum concentrations at about 30 fmol/mg protein. In the male this level then remained relatively constant throughout the time of study (60 days), whereas in the female the concentration decreased gradually over a period of 12–15 days to a basal level of 10 fmol/mg protein. A temporal study on the short- and longterm effects of ovariectomy on the concentration of estrogen binding sites in the kidney cytosol was also carried out. Shortly after gonadectomy (2–12 h) no effect was detected. During 20–48 h after the operation a 75% increase in the receptor level was seen. The results indicate a multihormonal control of the estrogen binding protein in the kidney similar to that seen in the liver. Furthermore, the data suggest that estradiol down-regulate its own receptor. The results are discussed in relation to present concepts on the actions of estrogens and the metabolism of vitamin D 3.