Oophorectomized Rats Research Articles

Effects of the beta3 adrenergic receptor agonist on developmental obesity in oophorectomized rats.

In this study, we evaluated the anti-obesity effects of selective beta3 adrenergic receptor agonist (ARa) and/or a diet in oophorectomized (OVX) treatment in obese rats. Ten-week-old female Sprague-Dawley rats were divided into 4 groups: (1) OVX; (2) OVX treated with beta3 ARa, BRL 35 135; (3) sham-operated controls (sham group); (4) sham-treated with beta3 ARa (sham+ARa group). These four groups were divided into two groups, one on ad libitum diet, and the other on a diet of limited chow. The effects of beta3 ARa on body weight, intraabdominal fat weight, adipocyte volume, serum lipid content, and serum leptin were measured after 4 weeks had been completed. On both the ad libitum and the limited diet, ARa significantly reduced the ratio of intraabdominal fat and body weight (IAF ratio) regardless whether in the OVX or sham group, although ARa had no influence on weight gain. On the ad libitum diet, the serum leptin was significantly increased after OVX, and significantly reduced after ARa administration. ARa significantly reduced the volume of intraabdominal adipocytes. We conclude that ARa reduces intraabdominal fat without reducing body weight in oophorectomized rats. The serum parameter affected differently to rats on the ad libitum diet and on the limited diet.

Restoration of fertility in oophorectomized rats after tubo-ovarian transplantation.

Improved microsurgical techniques for en bloc vascularized adnexal isograft in the rat is described. The graft of the right ovary together with its fallopian tube and upper third of uterus was transplanted orthotopically with end-to-side anastomoses between the donor aortic segment and recipient aorta and between the donor vena cava segment and recipient inferior vena cava, with end-to-end anastomosis of the donor and recipient uterus in a syngeneic, bilaterally oophorectomized rat. All transplantations were successful in terms of immediate vascular patency rate (10/10, 100%). Evidence of resumed ovarian function was obtained in 9 out of 10 rats (9/10, 90.0%) by histological demonstration of the vaginal smear, in which pregnancies were achieved in six rats (6/10, 60.0%) and six litters of healthy offspring were delivered 9 weeks later after transplantation. These results suggest that microsurgical ovarian transplantation provide a new and potential experimental model for the study of fertility restoration in humans.

The effect of estrogen-replacement therapy on clitoral-cavernosal tissue in oophorectomized rats: a histo-quantitative study by image analyzer.

Sexual dysfunction is an important problem for aging females. However, little attention has been paid to female sexual dysfunction. The clitoris is an important organ for physiological sexual function in females. There is a close relationship between the presence of sexual complaints and levels of estrogen. Using the rat as an experimental model, we evaluated the effect of estrogen-replacement therapy and its timing on clitoral-cavernosal collogen fiber content after oophorectomy. Four-month-old female Wistar rats (n = 36) weighing 230-250 g were used. They were categorized into four groups: oophorectomized (Group 1: n = 10); oophorectomized delayed estrogen replacement (group 2: n = 10); oophorectomized + immediate estrogen replacement (group 3: n = 10); and sham operated (group 4: n = 6). The estrogen replacement used was 17-beta-estradiol. All rats were euthanized at the same age. The specimens were stained with Masson's trichome technique, and computerized image analysis was used to quantify the collagen-fiber content of clitoral-cavernous tissue. The clitoral collagen-fiber percentages in the different groups were as follows: group 1: 64.17 +/- 5.01%; group 2: 62.57 +/- 5.37%; group 3: 56.33 +/- 3.85%; group 4: 51.48 +/- 6.37%, respectively. Although there was a tendency in the untreated group for a higher collagen-fiber content, no statistically significant difference was found among groups (P > 0.05). Although the results of this study were not statistically significant, estrogen did appear to decrease clitoral-cavernosal collagen-fiber content. These findings may be important in the pathophysiology of postmenopausal female sexual dysfunction.

Insulin insensitivity and delayed transcapillary delivery of insulin in oophorectomized rats treated with testosterone.

The importance of transcapillary insulin delivery as a regulated step was explored in an insulin resistant rat model. Oophorectomized female rats were exposed to testosterone (OVX + T) for 8 weeks and examined with insulin clamps, muscle microdialysis, and analyses of insulin distribution kinetics. The results were compared with those obtained in sham-operated control rats. After OVX + T, onset of glucose uptake in skeletal muscle was significantly (P < 0.001-0.05) delayed compared with controls as measured by the glucose infusion rate (GIR) during a euglycaemic, hyperinsulinaemic clamp (5 mU kg-1 min-1). The increase in interstitial insulin concentrations was also significantly (P < 0.05) delayed (15-20% lower) in OVX + T treated rats compared with control rats, but to such a small magnitude that this alone could not explain the late onset of the insulin effect. Skeletal muscle capillary density, examined histochemically, was diminished (P < 0.01-0.001) by 20-25% after treatment with OVX + T compared with control animals, as was the peripheral blood flow (P < 0.05) by 40-45%, measured with the microsphere technique. Insulin binding was reduced in proportion to the reduced (P < 0.01) vascular surface area by OVX + T treatment. Transcapillary transport rate of insulin, measured by comparisons of the kinetics of inulin and insulin spaces in muscle with time, tended (ns) to be lower after OVX + T compared with control rats (30-40%) as a reflection of the lower capillary surface area. The data suggest that the delayed onset of insulin action after OVX + T results from combined defects in the muscle cell at a postreceptor level and, to a lesser extent, from retarded transcapillary delivery of insulin.

Estudo ultraestrutural do colo uterino de ratas ooforectomizadas após aplicação de óleo de copaíba

Em virtude da extensa utilização empírica do óleo de copaíba em tratamentos ginecológicos, este trabalho visa realizar um estudo ultraestrutural do colo uterino de ratas após aplicação deste óleo. Foram utilizadas 12 ratas adultas distribuídas em 4 grupos: Água, Milho, Padrão e Copaíba. Os animais foram submetidos a ooforectomia bilateral e após 21 dias foi iniciada a aplicação das substâncias. A eutanásia foi realizada em datas pré-detreminadas (7º, 14º e 21º dias). Os grupos Padrão, Água e Milho apresentaram epitélio com duas a três fileiras de células poliédricas e núcleos de diferentes tamanhos e formas. Já no grupo copaíba, o epitélio era constituído de várias fileiras de células (8 a 10 fileiras). Concluiu-se que o óleo de copaíba promoveu aumento de fileira de células da camada epitelial com queratinização no colo uterino de ratas ooforectomizadas.

Aspectos Morfológicos e Morfométricos do Colo Uterino de Ratas Ooforectomizadas após Aplicação de Óleo de Copaíba

Objetivos: verificar o efeito do óleo de copaíba no colo uterino de ratas ooforectomizadas. Métodos: foram utilizadas 120 ratas adultas distribuídas em 4 grupos: as que receberam aplicação de óleo de copaíba, óleo de milho, água e um grupo sem tratamento. Todos os animais foram submetidos a ooforectomia bilateral e posteriormente mantidos em gaiolas por um período de 20 dias antes de iniciar a aplicação das substâncias. Estas foram administradas via vaginal na dose de 0,3 ml, diariamente, uma vez ao dia até os dias determinados para o sacrifício (7º, 14º e 21º), sendo sacrificados de cada grupo 5 animais por dia. Resultados: todos os animais do grupo copaíba apresentaram epitélio exuberante, estratificado pavimentoso queratinizado, em torno de 10 fileiras de células epiteliais, e lâmina própria com tecido conjuntivo denso, rico em fibroblastos, fibras colágenas, inúmeros vasos sanguíneos e alguns leucócitos. Conclusões: o óleo de copaíba utilizado neste modelo experimental promoveu espessamento do epitélio do colo uterino, que se apresentava pavimentoso estratificado com queratinização, além do espessamento progressivo deste epitélio no decorrer dos dias de estudo.

Speed of sound, bone mineral density and bone strength in oophorectomized rats.

The aim of this study was to determine the sensitivity of bone mineral density (BMD), ultrasounds (SOS) and resistance to torsion (T) to detect experimental osteopenia induced in rats 3 and 6 months after ooforectomy. Seventy-four rats were used, divided into four groups, ooforectomized rats analysed 3 and 6 months after the operation and their respective control groups, in which BMD (Hologic QDR 1000 S/N 277), SOS (DBM Sonic 1200) and T (adapted test machine) were determined in the right femur. The results of the three techniques distinguished the ooforectomized groups from the controls, both 3 and 6 months after the ooforectomy, obtaining more significant differences with BMD (P = 0.0006, P = 0. 001, respectively) than SOS and T, where a significance of only P = 0.05 was obtained. In the correlation study among the three techniques, a significant correlation was observed between BMD and SOS (r = 0.39, P = 0.0008), as well as between BMD and T (r = 0.31, P = 0.03). However, significance was not observed between the SOS and T tests. In the study of sensitivity and specificity of the techniques used to detect the osteopenia caused by the ooforectomy, by means of calculation of the area under the receiver operation characteristic (ROC) curve, it was proven that although the three techniques distinguished between the two analysed populations, BMD presented an area under the ROC curve that was superior (0.87, 0.85) to that obtained with SOS (0.73, 0.67) and T (0.73, 0.68), both 3 and 6 months after the operation.

Protective Effect of the Selective Estrogen Receptor Modulator LY117018 on Rat Vaginal Candida albicans Colonization

Although we know that estrogen promotes vaginal colonization with Candida albicans in oophorectomized rats, the availability of selective estrogen receptor modulators (SERMs) raises the question of whether these compounds may influence the susceptibility of vaginal epithelium to Candida colonization. We inoculated rats with viable C. albicans 2 days after treatment with oil vehicle (controls), estradiol cypionate or the proprietary SERM, LY117018. LY117018 prevented colonization by a clinical isolate of C. albicans. In contrast, rats treated with estradiol cypionate remained colonized for up to 10 days after initial inoculation with viable yeast. In vitro tests demonstrated that both estradiol-17β and LY117018 promoted growth at a 1 × 10^–9 M concentration, whereas both compounds suppressed yeast growth at a higher (1 × 10^–6 M) concentration. The effect of LY117018 on vaginal colonization could not be predicted on the basis of in vitro investigation. We conclude that the protective effect of LY117018 resulted from an indirect effect on the host and not from its effect directly on the microorganism.

Oophorectomy-Induced Osteopenia in Rats in Relation to Age and Time Postoophorectomy

Oophorectomized (OVX) rats served for many years as a popular model for ‘postmenopausal’ osteoporosis in spite of the fact that the rat continues to grow during these experiments. We performed OVX in rats at 1, 3, 6 and 10 months of age and compared the histomorphometric (bone size, bone trabecular and cartilage volume in different areas) and chemical (ash, Ca, P and Mg content) parameters at 2, 6, 8 and 20 weeks post-OVX (2–20 weeks) to those of sham-operated rats. Significant differences were observed only in the animals that were OVX at a young or young-mature age, i.e. mainly at 1 and 3 months and some of the rats at 6 months of age. There were no changes in bone ash and mineral contents in the OVX animals in comparison to sham-operated rats, except 2 weeks post-OVX in the 1-month-old rats where these variables were reduced. The most significant finding was a reduction in the metaphyseal bone volume. This was observed in the rats OVX at 1, 3 and 6 months of age, but not in those OVX at 10 months. In the young OVX rats there was also an increase in epiphyseal cartilage volume. The epiphyseal and diaphyseal bone volumes were not different between the groups at any time postsurgery, explaining the lack of differences in bone ash and mineral contents. There were no significant changes in the results of the histomorphometric studies between OVX and sham-operated rats when surgery was performed at 10 months of age. Since OVX exerts significant changes only in young rapidly growing rats, this approach is an inappropriate model for postmenopausal osteoporosis, which occurs long after bone growth has ended.

Inhibitory effects of female sex hormones on urinary stone formation in rats

The effects of female sex hormones on urinary stone formation are not known. This study was conducted to investigate the effects of these hormones on stone formation by using an ethylene glycol (EG) and vitamin D-induced rat urolithiasis model. Adult female Wistar rats were fed the same diet for four weeks and were then divided into four groups (N = 10 each). One group was administered 0.5 ml of olive oil three times per week for four weeks as a control. The other three groups were administered 0. 5 microg of vitamin D3 and 0.5 ml of 5% EG three times per week for four weeks. The rats in two of these three groups were oophorectomized, and the rats of the remaining group underwent a sham operation on the day before the start of the four-week treatment period. One of the two oophorectomized groups was then administered a supplementation of female sex hormones (0.1 mg of estrogen and 2.5 mg of progesterone 3 times per week for 4 weeks). On the first day of the fifth week of the experimental period, the degree of crystal deposition was determined histologically, and the calcium content in renal tissue was measured. We also investigated the level of osteopontin (OPN) mRNA in renal tissues by Northern blot analysis. OPN is a matrix protein thought to be a promoter of stone formation. The urinary oxalate excretion, crystal deposition and calcium content in renal tissue and the expression of OPN-mRNA were greater in the oophorectomized rats compared with the controls, and the same parameters were inhibited by the female sex hormone supplementation. These results suggest that female sex hormones can inhibit renal crystal deposition in EG-treated rats by suppressing the urinary oxalate excretion and the expression of OPN.

Clinical efficacy of raloxifene in postmenopausal women

A new class of compounds known as selective estrogen receptor modulators (SERMs) may possess the optimal combination of characteristics desirable in a drug designed for use in postmenopausal women. Among this class of compounds, raloxifene is the most studied and is currently available for clinical use in some countries for the prevention of osteoporosis in post-menopausal women. Raloxifene is a non-steroidal benzotiophene derivative shown to prevent bone loss at axial and appendicular sites and reduce serum cholesterol, like estrogen, in oophorectomized rats and in postmenopausal women. In animal models, unlike estrogen, raloxifene does not stimulate breast or uterine tissues. These appealing attributes make raloxifene a potential treatment for osteoporosis and other menopause related risks in middle aged and elderly women. Multicenter studies have been performed in early postmenopausal women, randomly assigned to receive raloxifene 30, 60, or 150 mg/day or placebo. All subjects received a calcium supplement. Bone mineral density, which was measured twice a year over 24 months by dual X-ray absorptiometry, decreased significantly at all skeletal sites with placebo, and significantly increased with raloxifene at the spine, hip, and total body at the three doses. At 24 months, the mean increase with raloxifene 60 mg compared with placebo was 2.4% at the lumbar spine and at the total hip, and 2% at the total body. Markers of bone formation (serum osteocalcin and bone specific alkaline phosphatase) and of resorption (urinary CrossLaps™) decreased significantly to the premenopausal range within 3–6 months of treatment with raloxifene. In addition, total serum and low-density lipoprotein cholesterol decreased significantly in all raloxifene therapy groups in a dose-related fashion. Serum HDL-cholesterol and triglycerides were not significantly changed by therapy. The most commonly observed side-effect was hot flushes, with patients taking raloxifene reporting a slightly higher rate of flushes (25%) than those on placebo (18%). This adverse event usually occurred within the first few months of therapy, was generally mild, and did not result in excess study dropout (raloxifene 1.5%, placebo 2.1%). Preliminary 2-year data indicated that raloxifene is not associated with an increased risk of breast cancer. In summary, the clinical efficacy and safety of raloxifene is very promising and this compound will offer a particularly attractive choice for postmenopausal women.

Usefulness of Serum Pyridinoline Cross-Linked Carboxy-Terminal Telopeptides of Type I Collagen and Osteocalcin in the Study of the Bone Resorption Rate in Oophorectomized Rats

The aim of this work was to determine sensitivity and specificity of serum pyridinoline cross-linked carboxy-terminal telopeptides of type I collagen (ICTP), a new biochemical marker of bone resorption, in order to study the rate of bone resorption associated with osteopenia development after oophorectomy in rats. The diagnostic accuracy of the bone formation marker osteocalcin (BGP) was also evaluated. Twelve-week-old female Wistar rats were used: (1) control group: sham-operated, treated with a placebo (n = 25); (2) OOX: oophorectomized rats treated with a placebo (n = 12), and (3) OE: oophorectomized rats treated with 17α-ethinyl estradiol 0.1 mg/kg/day for 3 months. The rats were sacrificed after treatment, and lumbar bone mineral density, BGP, and ICTP (serum assays specific for rat) were determined. As expected, OOX animals developed osteopenia. OOX rats showed a significant decrease (p < 0.05) in bone mineral density as compared with the control group, and OE rats showed no significant differences with respect to the control group. With respect to biochemical markers of bone remodeling, the OOX group showed a significant increase in BGP and ICTP (p < 0.005 and p < 0.05, respectively) with respect to control rats. However, the values of BGP and ICTP were similar in the OE group and in control animals. Areas under receiver operation characteristic curves corresponding to BGP and ICTP were 95 and 87%, respectively (p = 0.523). The results of the present work show that BGP and ICTP, the new resorption assay developed for rats, are reliable markers to be used in the study and follow-up of bone remodeling in OOX rats.

Effects of Progestins on the Metabolism of Cancellous Bone in Aged Oophorectomized Rats

The effects of progestins on bone loss in female oophorectomized (ovx) rats were evaluated. One-year-old Sprague-Dawley rats were divided into eight groups: (1) beginning controls (control); (2) sham-operated controls (sham); (3) ovx; (4) ovx treated with estrogen (ovx + E); (5) ovx treated with progesterone (ovx + P); (6) ovx treated with estrogen and progesterone (ovx + E + P); (7) sham group treated with estrogen (sham + E); and (8) sham group treated with progesterone (sham + P). Immediately after surgery, the rats in the hormone injected groups were subcutaneously (s.c.) injected daily for 15 weeks with estrogen (17-β-estradiol, 0.01 mg/kg in ethanol), or progesterone (4-pregnene-3,20-dione, 0.1 mg/kg in ethanol), or both. At the end of 15 weeks, the bone mineral density (BMD) and bone histomorphometry of the rats’ lumbar vertebrae and serological parameters were measured. In the sham, ovx, and ovx + P groups, treatment with progesterone alone did not maintain the BMD in the lumbar vertebrae, but in the ovx + E and ovx + E + P, sham + E, and sham + P groups, progesterone did not inhibit the action of estrogen in the aged ovx rat model. BMD in the sham + P group was significantly higher than in the sham group (270.8 ± 10.8 mg/cm 2 versus 253.6 ± 10.2 mg/cm 2; p < 0.01). Bone histomorphometry revealed that bone volume (BV/TV) increased more in the ovx + E + P group than in the ovx + E group and more in the sham + P group than in the sham group, but not significantly. The ovx + E, ovx + E + P, sham + E, and sham + P groups showed no significant differences in the bone formation and resorption parameters, but the bone formation variables tended to increase in the ovx + E + P and sham + P groups. We concluded that progesterone alone cannot prevent bone loss or the increase in turnover after ovx and that estrogen, not progesterone, accounted for all of the bone activity in this study. It seems doubtful that progesterone inhibits the action of estrogen, and in fact may have a beneficial effect on bone metabolism.

Effects of LY-117018 HCl on bone remodeling and mineral density in the oophorectomized rat

LY-117018 HCl is a recently developed, selective estrogen receptor modulator and an analog of raloxifene. Its mode of action on the skeleton is similar to that of estrogens, although it does not have the same side effects. The aim of the current study was to compare the effects produced by the administration of 17alpha-ethinyl estradiol (0.1 mg/kg/day) and LY-117018 HCl (1 mg/kg/day) on bone remodeling, bone mineral density, and body and uterus weight in sham-operated and oophorectomized rats (experimental model of postmenopausal osteoporosis). Twelve-week-old female Wistar rats were used. Treatment was given for 3 months after oophorectomy or sham operation. Bone mineral density was determined in the lumbar spine (L2, L3, and L4) and in the left femur with use of a Hologic QDR 1000 (S/N 277) densitometer. Bone remodeling was estimated with use of the formation markers osteocalcin (bone gla protein) and alkaline phosphatase and the resorption markers type I collagen carboxyterminal telopeptide and tartrate-resistant acid phosphatase. The newly developed derivative of raloxifene, LY-117018 HCl, offsets the reduction in bone mineral density and the accompanying increase in bone remodeling markers observed in oophorectomized rats compared with control animals. 17Alpha-ethinyl estradiol also prevents the loss of bone mass attributed to oophorectomy, but this is accompanied by an increase in body mass and a greater increase in uterus weight than that observed after treatment with LY-117018 HCl.

Phytoestrogens Reduce Bone Loss and Bone Resorption in Oophorectomized Rats

To examine a potential role for phytoestrogens in postmenopausal bone loss, the oophorectomized (OOX) rat model has been used in three studies to investigate the effects of the phytoestrogens coumestrol, zearalanol and a mixture of isoflavones on estrogen-dependent bone loss. In the studies of coumestrol and zearalanol, the rats were allocated to a control group, a phytoestrogen-treated group (1.5 μmol coumestrol or 3.1 mmol zearalanol twice per week, intramuscular) or, in the coumestrol study, an estrogen-treated group (28.1 nmol, intramuscular). In the isoflavone study, the rats were allocated to a control group, an estrogen treated group or a treatment group that received 131.25 mg of phytoestrogens per week incorporated into the nonpurified rat diet. Bone mineral density was measured globally and at the spine and femur at base line and 6 wk post-oophorectomy. In the coumestrol study, blood and urine samples were collected. Compared with the control group, rats receiving coumestrol and zearalanol had significantly reduced bone loss at all sites measured. The estrogen-treated group had significantly greater bone density than the control and the coumestrol-treated groups in the spine and global measurements. Coumestrol reduced urine calcium excretion and the bone resorption markers pyridinoline and deoxypyridinoline after 1 wk of treatment. Oral isoflavone phytoestrogens had no effect on oophorectomized rats including bone loss at the dose used. Thus, for the first time, the bioactivity of coumestrol and zearalanol in preventing bone loss has been demonstrated in a well-recognized model of postmenopausal bone loss.

Iontophoretic transdermal absorption of insulin and calcitonin in rats with newly-devised switching technique and addition of urea

The effect of urea and reversing polarity of electrodes (switching technique) in iontophoresis was investigated in order to get a better transdermal absorption of peptide drugs, insulin and calcitonin, and to reduce dermal irritation caused by the iontophoresis. Two cells with an electrode were set on the hair-removed abdominal skin of diabetic or oophorectomized rats. After putting peptide solution into the anode side or both of the cells, an electric current with pulsed rectangular wave form (4 kHz, 50% duty) was passed through the skin for 2 h at 0.075 mA cm −2 (insulin) and for 50 min or 2 h at 0.015 mA cm −2 (calcitonin). Absorption of insulin and calcitonin was estimated from the reduction of glucose and calcium levels in the plasma of the rats, respectively. When the polarity of electrodes was reversed at intervals of 20 min for insulin and 25 min for calcitonin, absorption of the drug was effectively enhanced. The addition of urea to the insulin solution together with the switching technique brought about a remarkably facilitated absorption of insulin. Moreover, comparison of the skin conditions between switching and non-switching experiments suggested that irritation of skin could be reduced by employment of the switching iontophoresis.

Relationship between tobacco smoke and uterotropic effect of estrogen

Female rats aged 3.–3.5 months were daily exposed for 2 h to 2.25% tobacco smoke in a 20-liter chamber for 3 weeks. A week after the beginning of the experiments, all rats were subjected to bilateral oophorectomy. Some of them were injected with estradiol in a daily dose of 2 μg or diethylstilbestrol in a daily dose of 1 μg for 10 days. Tobacco smoke exposure led to an increase in the uterus weight in oophorectomized rats, and combined exposure to tobacco smoke and estrogens resulted in an increase in the proportion of intact (twisted) DNA in the uterus. These results can be explained by a relatively short term of tobacco smoke exposure (stimulation stage).

Effect of dehydroepiandrosterone sulfate on carnitine acetyl transferase activity and l-carnitine levels in oophorectomized rats

Alteration in energy metabolism of postmenopausal women might be related to the reduction of dehydroepiandrosterone sulfate (DHEAS). DHEA and DHEAS decline with age, leveling at their nadir near menopause. DHEA and DHEAS modulate fatty acid metabolism by regulating carnitine acyltransferases and CoA. The purpose of this study was to determine whether dietary supplementation with DHEAS would also increase tissue l-carnitine levels, carnitine acetyltransferase (CAT) activity and mitochondrial respiration in oophorectomized rats. Plasma l-carnitine levels rose following oophorectomy in all groups ( P<0.0001). Supplementation with DHEAS was not associated with further elevation of plasma l-carnitine levels, but with increased hepatic total and free l-carnitine ( P=0.021 and P<0.0001, respectively) and cardiac total l-carnitine concentrations ( P=0.045). In addition, DHEAS supplementation increased both hepatic and cardiac CAT activities ( P<0.0001 and P=0.05 respectively). CAT activity positively correlated with the total and free carnitine levels in both liver and heart ( r=0.764, r=0.785 and r=0.700, r=0.519, respectively). Liver mitochondrial respiratory control ratio, ADP:O ratio and oxygen uptake were similar in both control and supplemented groups. These results demonstrate that in oophorectomized rats, dietary DHEAS supplementation increases the liver and heart l-carnitine levels and CAT activities. In conclusion, DHEAS may modulate l-carnitine level and CAT activity in estrogen deficient rats. The potential role of DHEAS in the regulation of fatty acid oxidation in postmenopausal women is worthy of investigation.

Effects of continuous or cyclic administration of pamidronate on the skeleton in intact and oophorectomized young rats.

Bisphosphonates are potent inhibitors of bone resorption, and are therefore used for the treatment of various bone diseases including osteoporosis. We examined whether cyclic therapy with bisphosphonates in oophorectomized osteoporotic rats had any advantage over continuous treatment. We therefore treated intact and oophorectomized young female rats for 8 weeks with 1 and 5 mg/kg/day of pamidronate. The 8-week treatment was given continuously for 6 days/week or intermittently, i.e. 6 days of pamidronate (APD) and 3 weeks off, for 2 cycles. We found an increase in tibial wet and ash weight and in the mineral content in oophorectomized rats treated continuously or intermittently with APD in comparison to nontreated oophorectomized animals. Histomorphometric analysis showed an increase in the volume of metaphyseal cartilage and bone. No changes were found in the volume of epiphyseal or diaphyseal bone. Pamidronate had very little effect on the bone of intact rats. Pamidronate seems to be more effective in inhibiting bone resorption in bone that undergoes rapid turnover (i.e. in oophorectomized animals) when compared to bone with low turnover (intact rats). Although the results of cyclic treatment were similar to those of continuous treatment, we have to remember that cyclic therapy may be more advantageous since animals receiving cyclic therapy received only 25% of the dose of rats continuously treated.

P091 The effect of ovarian hormone on the bone loss in oophorectomized rats

P091 The effect of ovarian hormone on the bone loss in oophorectomized rats