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Influence of adrenalectomy and ovariectomy on gonadotrophin secretion.

In order to gain additional information on the effects exerted by adrenal hormones on gonadotrophin secretion, adult female rats have been submitted concomitantly to adrenalectomy and ovariectomy; ovariectomized animals with intact adrenals served as controls. Serum levels and pituitary concentrations of LH and FSH have been measured on post-operation days 1, 2, 7, 14 and 28. It has been found that ovariectomy, when performed alone, induces a progressive but delayed release of LH and a rapid and constant release of FSH. Ovariectomy exerts only minor effects on the concentrations of pituitary LH, while providing a strong stimulus to the intrapituitary accumulation of FSH. Adrenalectomy, superimposed on ovariectomy, advances the release of LH, and at the 4-week interval, increases serum levels of this gonadotrophin to well above those found in animals submitted only to ovariectomy; the absence of the adrenals does not significantly alter the release of FSH. Adrenalectomy, added to gonadectomy, strongly facilitates the accumulation of LH in the anterior pituitary, but decreases the resynthesis of FSH. In conclusion, these data suggest that one or more factors of adrenal origin may: (1) inhibit the release of LH without affecting the release of FSH; (2) prevent the post-gonadectomy accumulation of LH in the anterior pituitary and facilitate the re-accumulation of FSH.

Adrenalectomy↗

Reproductive senescence in female C57BL/6J mice: ovarian impairments and neuroendocrine impairments that are partially reversible and delayable by ovariectomy.

Ovarian and neuroendocrine impairments were examined before and after the age-correlated loss of estrous cycles in C57BL/6J female mice. The role of ovarian secretions in inducing neuroendocrine impairments before and after the loss of estrous cycles was also examined by determining neuroendocrine impairments after prolonged ovariectomy. Young (6-month-old) cycling, middle-aged (12-, 14-, and 16-month-old) cycling or acyclic, and old (18-month-old) acyclic mice were used. Ovarian impairments were assessed by grafting old ovaries into young hosts. Neuroendocrine impairments were assessed by grafting young ovaries into middle-aged and old hosts, ovariectomized either at grafting or 2 months before, and by inducing a LH surge in mice that had been ovariectomized for 4 days, 1 month, or 2 months. One group of 16-month-old and one group of 18-month-old mice were also ovariectomized at 6 months of age; these groups were used to examine the steroid-induced LH surge. The LH surge was induced by inserting sc a single priming estradiol (E2) implant, followed by two more (surge-inducing) implants 6 days later; 33 h after the second implantation, mice were decapitated (1800 h). The number of estrous cycles supported by middle-aged and old ovaries grafted into young hosts was reduced by more than 90% compared with that in young ovaries. The number of estrous cycles supported by middle-aged and old hosts given young ovarian grafts was reduced by 60% and 90%, respectively, compared with that in young hosts. Middle-aged and old hosts also had progressively longer estrous cycles than young hosts. Levels of the E2-induced LH surge in middle-aged and old mice were also reduced by 60% and 90%, respectively, compared with levels in young mice. In old acyclic mice, ovariectomy for 2 months partially reversed impairments in the LH surge and partially restored the ability to support cycles with young grafts; these functions, normally 90% impaired in old mice, were only 60% impaired after prolonged ovariectomy. Moreover, ovariectomy 2 months before grafting in old hosts resulted in shorter estrous cycles and 60% fewer pituitary adenomas. In middle-aged cycling mice, ovariectomy for 2 months did not affect impairments in the LH surge or in the ability to support estrous cycles with young grafts; these functions remained 60% impaired in middle-aged mice ovariectomized for 2 months. If mice were ovariectomized when young, the age-correlated impairments of the E2-induced LH surge at 16 months were largely prevented.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Augmentation of pituitary responsiveness to luteinizing hormone/follicle stimulating hormone-releasing factor (LH-RF) as a result of acute ovariectomy in the four-day cyclic rat.

Within 6 h of ovariectomy in adult rats with 4-day estrous cycles, plasma FSH titers were significantly elevated above those of sham-operated controls at all stages of the estrous cycle, whereas plasma LH concentrations were raised by ovariectomy only during diestrus day 2, proestrus or estrus. A single intravenous injection of a partially purified extract of ovine stalk-median eminence tissue (LH-RF) into sham-operated control rats or incubation of pituitaries from similar rats with the same releasing factor extract elevated LH and FSH output at all stages of the cycle. This response to LH-RF was related to the stage of the estrous cycle, maximal pituitary responsiveness occurring on proestrus. Ovariectomy 6 h before administration of LH-RF significantly augmented pituitary LH and FSH responsiveness both in vivo and in vitro. This elevation in hypophyseal responsiveness observed in vitro followed a cyclic pattern which could be superimposed on the normal cyclic changes in pituitary responsiveness, whereas the cyclic increase in pituitary LH responsiveness to LH-RF in vivo following acute ovariectomy was first detectable 16 to 18 h earlier than in intact controls, that is, on late diestrus day 2 rather than on the morning of proestrus. These results indicate that acute ovariectomy can augment pituitary responsiveness to LH-RF and can also advance the onset of the cyclic augmentation of pituitary responsiveness to LH-RF during the 24 h immediately preceding the ovulatory gonadotropin surge. Possible explanations for these effects are discussed.

Animals↗

Effects of antibody to oestrogen or of ovariectomy on the incorporation of [35-S]methionine into brain protein and on gonadotrophin levels during the oestrous cycle in the rat.

The incorporation of [35S]methionine into protein of the anterior pituitary and discrete brain areas was measured following the administration of antibodies to oestrogen, ovariectomy, or adrenalectomy on the afternoon of dioestrus. The antibody to oestrogen deleted the circadian rhythms of methionine incorporation normally observed in the various brain areas together with the peaks of incorporation normally observed in the median eminence area and anterior pituitary on the evening of pro-oestrus. The peaks of incorporative activity normally observed in the preoptic area and amygdala (relative to the putamen) at 03.00 h on the day of pro-oestrus were also deleted. Administration of the antiserum on the morning of pro-oestrus failed to alter the pattern of methionine incorporation normally observed on the evening of pro-oestrus. Ovariectomy performed at 16.00 h of dioestrus blocked the preovulatory rise of luteinizing hormone (LH) (as did the antibody to oestrogen) and inhibited the peak of methionine incorporation normally observed in the anterior pituitary on the evening of pro-oestrus. However, for the peak in the median eminence to be inhibited, ovariectomy had to be performed on the morning of the preceeding oestrus. Adrenalectomy alone, or adrenalectomy with ovariectomy, performed on the afternoon of dioestrus did not affect the levels of methionine incorporation in the brain or anterior pituitary at 18.00 h on the day of pro-oestrus. Animals which had been ovariectomized and injected with 2-5 mug oestradiol benzoate on the morning of oestrus showed significantly increased levels of methionine incorporation in all the brain areas and the anterior pituitary at 18.00 h of expected pro-oestrus. The administration of antibody to oestrogen to a similar group of animals on the afternoon of expected dioestrus inhibited the rise at 18.00 h of expected pro-oestrus. The apparent discrepancy between the results obtained with ovariectomy and the antiserum appeared to be due to the ability of the antiserum to neutralize the activity of oestrogens retained by the tissues. The present results suggest that the changes in incorporation of methionine into protein in the brain and anterior pituitary are brought about by the action of endogenous oestrogen: there appears to be a steady summative effect on the median eminence throughout the oestrous cycle together with a short-lived effect occurri4g during pro-oestrus and affecting the anterior pituitary.

Adrenalectomy↗

Infantile ovariectomy potentiates the stimulatory effect of oestrogen/progesterone on LH secretion in the rat.

Ovariectomy of prepubertal rats (9 days of age) eliminates the ability of the opiate peptide FK 33-824 to inhibit LH secretion when tested 19 days later. We have investigated whether this removal of opiate inhibition would modify the LH/FSH response to stimulation with oestradiol benzoate/progesterone priming. Ovariectomy of rats during infancy (9 days after birth) amplifies the stimulatory effects of these steroids on LH/FSH secretion when tested 19 days later. This amplification was not seen in rats ovariectomized before (day 24) or after puberty (day 43) and tested 19 days later. The pituitary content of LH/FSH does not appear to contribute to this phenomenon, though increased responsiveness to injected gonadotrophin-releasing hormone (GnRH) is clearly involved; ovariectomy at day 9 is considerably more effective than ovariectomy at day 24 of life in enhancing the response to GnRH. We conclude that infantile ovariectomy either removes, or prevents the development of, a hypothalamic inhibitory mechanism which normally modulates the responsiveness of the pituitary to stimulation with GnRH.

Animals↗

The influence of early age mastectomy and unilateral ovariectomy on reproductive performance of the bovine.

The effects of mastectomy and unilateral ovariectomy and their interaction during the postpartum period were examined in 26 Angus heifers. At birth, the animals were assigned to a 2 x 2 factorial arrangement of treatments: mastectomy and unilateral ovariectomy, mastectomy, unilateral ovariectomy and unoperated suckled control. Surgeries were performed at approximately 2 months of age, and animals were observed through three consecutive postpartum intervals (PP1, PP2, and PP3). There were no significant influences of mastectomy or ovariectomy on age at puberty, age at first conception or services required for first conception. Mastectomy reduced the number of days from parturition to ovulation (PP1, 32.1 vs 52.5, P less than .01; PP2, 21.6 vs 59.9, P less than .01; PP3, 20.6 vs 46.7, P less than .01) The interval from parturition to first estrus was shorter for heifers in the mastectomized group (PP1, 45.3 vs 76.2, P less than .05; PP2, 28.7 vs 69.9, P less than .01; PP3, 32.4 vs 62.3, P less than .05) as was the interval from parturition to conception during PP2 (60.0 vs 104.9, P less than .05). The interval between calvings was shorter for heifers in the mastectomized group than for controls, but the difference was significant only between the second and third parturitions: 338.5 vs 399.2 (P less than .01). Mastectomy reduced the standard deviation for the interval between parturition 2 and parturition 3 (55.9 vs 15.9; P less than .01), the interval between parturition and return to estrus in PP2 (56.3 vs 11.4; P less than .01) and the interval from calving to conception PP1 (92.2 vs 31.4; P less than .01). Unilateral ovariectomy did not have a significant influence on any of the postpartum intervals, nor were there any significant interactions.

Age Factors↗

Histo-anatomy of the proximal femur in rats: impact of ovariectomy on bone mass, structure, and stiffness.

BACKGROUND: Hip fractures are the most devastating consequence of osteoporosis in humans. Since the ovariectomized (ovx) rat is a useful model of estrogen-deficient osteoporosis, the purposes of this study were to describe the histo-anatomical features of the rat hip and to determine changes in the proximal femur induced by ovariectomy to evaluate the use of this skeletal site for future bone studies. METHODS: Changes in body mass and composition and in bone mineral content and density were determined by DEXA at 12 weeks after ovariectomy. Gross and histo-anatomy of the rat hip was studied by light microscopy and histomorphometry. Cancellous and cortical bone changes induced by ovx at the femoral midneck were determine using dynamic, static, and structural histomorphometric techniques. The stiffness of the femoral neck was determined by biomechanical testing, and the results were correlated with histological observations and the histomorphometric data. RESULTS: The bony structures of the rat hip, articular cartilage, and muscular and capsular attachments are very similar to the human. Rats, however, have an active growth plate and a well-vascularized periosteum covering the intracapsular portion of the femoral neck, which is different from the adult humans. Rats in the sham and ovx groups exhibited similar biological variations in the thickness of the femoral neck and epiphyseal bone and cartilaginous composition. Ovariectomy promoted periosteal modeling and induced endocortical and cancellous bone remodeling, with a net loss of bone mass due to excess bone resorption. The ovx-induced increase in resorption resulted in reduced trabecular number, thickness, and endocortico-trabecular connectivity, which likely contributed to less bone stiffness in ovx rats relative to the sham controls. CONCLUSIONS: There are numerous similarities in the structure and histology of the rodent and human hip. Skeletal changes induced by ovariectomy in rats, particularly those at the endocortical surface and in the cancellous bone, are very similar to changes observed in the proximal femur in osteoporotic women. In addition, ovx in the rat had compromised the biomechanical properties at the femoral neck, similar to what occurs in the postmenopausal women. Data presented here confirmed responsiveness of the proximal femur in rat to ovarian hormone deficiency, which appears to be a useful and relevant site to investigate mechanisms and interventions relative to human disease.

Absorptiometry, Photon↗

Acute effects of ovariectomy on wound healing of alveolar bone after maxillary molar extraction in aged rats.

Acute effects of ovariectomy on the bone wound healing processes after maxillary molar extraction in aged rats were examined by means of quantitative scanning electron microscopy (SEM), backscattered electron image (BSE) analysis and energy-dispersive X-ray (EDX) microanalysis. Six-month-old female rats underwent either sham operation or bilateral ovariectomy, and 7 days postoperatively, the maxillary first molars were extracted. On post-extraction days 7, 30 and 60, the dissected maxillary bone surfaces were examined by SEM to reveal the bone formative and resorptive areas around the extracted alveolar sockets. In addition, the resin-embedded maxillae were micromilled in the transverse direction through the extracted alveolar sockets, and the newly-formed bone mass on the buccal bone surfaces and within the extracted sockets was examined by BSE analysis. Compared with sham-operated controls, the extent of newly-formed bone mass on the buccal bone surfaces in OVX rats was significantly decreased, due to increased bone resorption. On the other hand, new bone formation within the extracted sockets was similar in the experimental groups. In EDX microanalysis of these newly-formed bone matrices, both Ca and P weight % and Ca/P molar ratio were similar in the experimental groups. Our results suggest that 1) acute estrogen deficiency induced by ovariectomy stimulates sustained bone resorption, but has less effect on bone formation, and 2) bone wound healing after maxillary molar extraction within extracted alveolar sockets is not significantly delayed by ovariectomy, but bony support by newly-formed bone mass on the maxillary bone surfaces at the buccal side of the extracted sockets is significantly decreased, due to increased bone resorption.

Acute Disease↗

The bisphosphonate alendronate (MK-217) inhibits bone loss due to ovariectomy in rats.

Estrogen deficiency in mammals is known to increase bone turnover and result in reduced bone mass. The bisphosphonate, 4-amino-1-hydroxybutylidene-1,1-bisphophonic acid disodium salt, alendronate (MK-217), is a potent inhibitor of bone resorption and was evaluated in this study for its ability to inhibit bone loss following ovariectomy in rats. Alendronate was administered sc in doses of 0.0, 0.056, 0.28, 1.40, and 7.0 mg P/kg/month, divided into two, four, or eight monthly subcutaneous injections for each dose, to female Sprague-Dawley rats (250-280 g) that underwent bilateral ovariectomy. Rats were sacrificed 12 weeks postovariectomy, the femora ashed, and the tibiae prepared for static and dynamic histomorphometric analyses. Femoral bone mass in vehicle-treated rats was reduced by 12% 12 weeks after ovariectomy compared to the nonovariectomized control group. In MK-217-treated rats femoral bone mass was significantly increased in a dose-dependent manner compared to either ovariectomized or nonovariectomized controls. Histomorphometric analysis showed significant increases in tibial trabecular bone volume with no decrease in osteoclast number. Doses delivered twice per month or eight times per month were equally effective in achieving the peak bone volume 12 weeks after ovariectomy. In conclusion, alendronate (MK-217) was effective in inhibiting bone loss due to estrogen deficiency in rats, and the magnitude of its effect was related primarily to the total amount of compound administered rather than the frequency of its administration.

Alendronate↗

The effect of ovariectomy on concentrations of plasma prolactin and LH and parental behavior in the domestic fowl.

The role of ovarian hormones in the expression of parental behavior and in the regulation of LH secretion was investigated in incubating commercial meat-type hens. After ovariectomy, incubating hens continued to incubate eggs normally and brooded day-old chicks given to replace eggs, in a manner similar to sham-ovariectomized control hens. The concentration of plasma LH increased significantly in incubating hens after ovariectomy while the concentration of plasma prolactin remained high. Plasma LH remained depressed in sham-ovariectomized incubating control hens. The increase in plasma LH in incubating hens after ovariectomy (3.92 +/- 0.7 ng/ml) was less than that following the ovariectomy of nonincubating, nonlaying hens (5.3 +/- 1.2 ng/ml). The two groups of hens differed in that plasma prolactin concentrations were high (527 +/- 7.4 ng/ml) in the incubating hens and low (70 +/- 9 ng/ml) in the nonincubating hens. Nest deprivation resulted in an increase in plasma LH in both ovariectomized and sham-ovariectomized incubating hens with a significantly larger increase occurring in the ovariectomized hens (8.5 +/- 1.41 ng/ml compared to 2.48 +/- 0.65 ng/ml). Nest deprivation resulted in a similar rapid decrease in plasma prolactin in both ovariectomized and sham-ovariectomized hens. Replacement of eggs with day-old chicks in ovariectomized or sham-ovariectomized incubating hens resulted in a rapid decrease in plasma prolactin and after 6 days, in an increase in plasma LH in the ovariectomized but not sham-operated hens. It is concluded that once incubation behavior is established, ovarian hormones are not required for its maintenance or the readiness to brood day-old chicks. Ovarian hormones do, however, suppress LH release during incubation while the high concentration of plasma prolactin supplements this suppression.

Animals↗

Morphological changes in the submandibular glands and in the X zone of the adrenal gland following ovariectomy in mice.

Morphological changes in submandibular glands of female mice following ovariectomy were studied morphometrically by light microscopy and ultrastructurally by electron microscopy. The X zone of the adrenal gland was examined in order to assess possible changes that might be expected to occur after ovariectomy. In submandibular glands, 1 to 4 weeks after ovariectomy, no changes were observed in percentages of the acinar, intercalated duct, and granular convoluted tubular areas occupying photomicrographs. However, an increase in the granular content of both intercalated duct and granular convoluted tubular cells was recognized. By contrast, the glandular picture 4 months after ovariectomy changed remarkably, resembling that of the male mouse both morphometrically and in terms of fine structure. In the adrenal cortex of control female mice, the X zone became thinner with aging. As compared with this, the X zone of ovariectomized mice at any time after the operation was thicker than that of controls. These observations suggest that the absence of ovarian hormones in the ovariectomized mouse may lead to prolonged functioning of X zone cells, which in turn may cause masculinization of the submandibular gland.

Adrenal Glands↗

Persistent bone-sparing effect of interleukin-1 receptor antagonist: a hypothesis on the role of IL-1 in ovariectomy-induced bone loss.

The recent finding that treatment with the interleukin-1 (IL-1) inhibitor, interleukin-1 receptor antagonist (IL-1ra) decreases bone loss and bone resorption in ovariectomized rats, strongly suggested that IL-1 mediates, at least in part, the effects of estrogen deficiency on bone resorption. Although in vitro studies have shown that IL-1 activates mature osteoclasts and stimulates osteoclastogenesis, the two main mechanisms by which estrogen deficiency stimulates bone resorption, it is still unclear whether IL-1 mediates both effects of estrogen deficiency in vivo. To investigate this matter, we have examined the changes in bone mineral density (BMD) which occur in ovariectomized rats after completion of 1 month of estrogen or IL-1ra treatment begun at the time of ovariectomy. Ovariectomy caused a marked decreased in BMD which was blocked by 17 beta estradiol and decreased by IL-1ra. Cessation of estrogen therapy was followed by a rapid induction of bone loss, indicating that estrogen blocks the activation and utilization of mature osteoclasts without depleting the bone microenvironment of osteoclast precursors and mature, inactive osteoclasts. In contrast, ovariectomized rats treated with IL-1ra maintained a stable bone density for the first 4 weeks after completion of the treatment. In these rats, bone loss resumed not earlier than 6 weeks after discontinuation of the IL-1ra treatment. Estrogen deficiency was necessary to unveil the bone-sparing effect of IL-1ra because in a control experiment in which rats were treated with IL-1ra for the 4 weeks before ovariectomy, BMD began to decrease immediately after ovariectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cortical bone mass, composition, and mechanical properties in female rats in relation to age, long-term ovariectomy, and estrogen substitution.

The study comprised 12 groups of female rats: 6 groups of intact rats killed at 2, 6, 9, 12, 15, and 24 months of age, 4 groups of rats ovariectomized at 6 months and killed together with the intact rats at 9, 12, 15, and 24 months of age, and 2 groups of rats (one intact and one ovariectomized) treated with estrogen (2 micrograms estradiol valerate/rat/week s.c.) for 8 months before they were killed at 24 months of age. The composition, dimensions, and mechanical strength of intact bone and bone collagen from femoral diaphyses were investigated in relation to age, ovariectomy, and estrogen administration. Up to 6-9 months of age, the axial length, percentage ash, density, and compressive mechanical stress increased, whereas percentage collagen decreased. An age-related increase in bone mass, cross-sectional area, and wall thickness and a decrease in mechanical quality of bone collagen were apparent from 2 to 24 months of age. An age-related periosteal bone formation and the absence of endosteal bone resorption were demonstrated in intact rats. Compared with intact rats, ovariectomy was followed by an increase in body weight, a tendency to reduced percentage ash and a depressed bone mass, cross-sectional area, and wall thickness of femoral diaphyses. The compressive mechanical stress of intact bone and the mechanical quality of bone collagen were unaffected by ovariectomy. Ovariectomy did not influence the periosteal bone formation but induced an endosteal bone resorption not present in the intact rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Short-term effects of ovariectomy: the opioid control of LH secretion in fertile climacteric and postmenopausal women.

The aim of this study was to evaluate the activity of opiate receptors involved in the regulation of LH secretion in relationship to ovariectomy. Menstruating fertile (n = 5) and climacteric (n = 7) patients and postmenopausal (n = 5) women who underwent therapeutical bilateral ovariectomy were studied in the first week postsurgery and LH plasma levels were evaluated after naloxone (4 mg in bolus plus 4 mg infusion/90 min), LHRH (10 micrograms + 10 micrograms iv) and saline administration. Two groups of fertile (n = 6) and postmenopausal (n = 6) subjects were studied as controls. Since the LH responsiveness to naloxone was impaired in climacteric patients after ovariectomy, the test was repeated in 5 of them after 1 and 6 months of estrogen-gestagen treatment (conjugated estradiol + noretisterone acetate), showing a significant increase in all patients in both cases. In four subjects treated with only gestagen, naloxone was still unable to significantly modify LH plasma levels. These results indicate that ovariectomy affects the activity of opiate receptors, resulting in the first week postsurgery LH rise inversely related to basal LH levels. Furthermore, these results indicate that one or six cycles of estrogen-gestagen treatment in ovariectomized patients similarly induces a restoration of the opiate receptors neuroendocrine activity.

Adult↗

The effect of ovariectomy and estradiol replacement on collagen and elastic fibers in the bladder of rats.

The authors quantified the collagen and elastic fibers in the bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 60 3-month-old Wistar rats. Group 1 remained intact; group 2 underwent bilateral ovariectomy and were sacrificed after 30 days; group 3 were sham operated and sacrificed after 30 days; group 4 had a bilateral ovariectomy and after 30 days were started on subcutaneous injections of 17beta-estradiol (10 microg/kg body weight) for 90 days; group 5 were sham operated and after 30 days were on started subcutaneous sesame oil replacement (0.2 ml/day) for 90 days; group 6 had a bilateral ovariectomy and after 30 days were started on subcutaneous sesame oil replacement (0.2 ml/day) for 90 days. Sirius red and Weigert's resorcin-fuchsin were used to stain collagen and elastic fibers on paraffin-embedded rat bladder sections. The M-42 grid system was used to quantitatively analyze the fibers. Ovariectomy had no effect on the volumetric density and absolute volume of the collagen and elastic fibers in the bladder wall of rats, or on the weight of the bladder. Estradiol replacement in castrated animals did not demonstrate any significant difference in the stereological parameters compared to the castrated group without hormonal replacement.

Animals↗

The effect of ovariectomy on biomarkers of urogenital ageing in old versus young adult rats.

The aim of this study was to compare the effects of ageing and ovariectomy on biomarkers of urogenital ageing in old and young-adult rats. Fisher 344 rats (18- and 3-months-old, n = 6 x 2) underwent ovariectomy. Age-matched sham animals received no intervention (n = 6 x 2). One month later, biomarkers of urogenital ageing were evaluated (light microscopic count of urethral and anal canal submucosal blood vessels, Western blot analysis of urethral, and anal canal submucosal collagen I and III and cytoplasmic p27(kip1) expression in the striated urethral and anal sphincters and levator ani and gel electrophoresis of isomyosin I proportion in these muscles) and compared in all groups (n = 24). All biomarkers of urogenital ageing studied were significantly increased in old compared to young-adult sham rats. Ovariectomy significantly increased these changes further in old versus young-adult rats with either smaller or larger differential effect than ageing compared to young-adult sham animals. Ovariectomy significantly exacerbates normative urogenital ageing changes in rats.

Aging↗

Animal model of menopausal depressive-like state in female mice: prolongation of immobility time in the forced swimming test following ovariectomy.

RATIONALE: The onset of menopause produces a depressive state in women, but the mechanism involved in menopause-induced depression is poorly understood. OBJECTIVES: Building upon previous studies that used the duration of immobility in male rodents during the forced swimming test as a behavioral measure of the depression-like state, we investigated whether the duration of immobility in female mice was altered following bilateral ovariectomy. We also evaluated the chronic effects of estradiol, antidepressants, scopolamine, and diazepam on both the duration of immobility and uterine weight. METHODS: We bilaterally resected the ovaries of ICR albino female mice at 9 weeks of age. The day after the surgery, drug treatment was started once per day for 2 weeks, after which, the behavioral test was administered. The duration of immobility was measured during the last 4 min of the 6-min trial. RESULTS: Bilateral ovariectomy significantly increased the duration of immobility. Chronic treatment with estradiol (15-30 microg kg(-1) day(-1)) prevented the prolongation of immobility following ovariectomy and produced a significant increase in uterine weight. Chronic treatment with imipramine, fluvoxamine, and milnacipran at 5, 10, and 15 mg kg(-1) day(-1), respectively, significantly reduced the duration of immobility, whereas treatment with scopolamine or diazepam (0.5, 1.0, and 2.0 mg kg(-1) day(-1) for both) was ineffective. CONCLUSION: Based on these results, we suggest that the prolongation of immobility in female mice following ovariectomy may be a useful tool for investigating menopausal depression.

Animals↗

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.

Age Factors↗