Ovariectomy

J p (2000) Daidzein is more efficient than genistein in preventing ovariectomy-induced bone loss in rats. J Nutr. 130 1675-81. 

Similar to the human studies, the animal studies are not entirely consistent, due to the different study designs (source and dose of soy protein/isoflavones time, method and length of administration age of rats, etc.). Nevertheless, a certain number of conclusions may be drawn. Overall, soy extracts or pure isoflavones show an osteoprotective effect in the ovariectomized rat model of menopausal bone loss. The time of administration is important and they must be given at the time of ovariectomy which allows prevention but not reversal of bone loss. Although the OVX-induced bone loss in the rat is a... 

The application of flavonoids for the treatment of various diseases associated with free radical overproduction is considered in Chapter 29. However, it seems useful to discuss here some studies describing the activity of flavonoids under certain pathophysiological conditions. Oral pretreatment with rutin of rats, in which gastric lesions were induced by the administration of 100% ethanol, resulted in the reduction of the area of gastric lesions [157]. Rutin was found to be an effective inhibitor of TBAR products in the gastric mucosa induced by 50%i ethanol [158]. Rutin and quercetin were active in the reduction of azoxymethanol-induced colonic neoplasma and focal area of dysplasia in the mice [159], Chemopreventive effects of quercetin and rutin were also shown in normal and azoxymethane-treated mouse colon [160]. Flavonoids exhibited radioprotective effect on 7-ray irradiated mice [161], which was correlated with their antioxidative activity. Dietary flavones and flavonols protected against the toxicity of the environmental contaminant dioxin [162], Rutin inhibited ovariectomy-induced osteopenia in rats [163],... 

Legan SJ, Tsai HW (2003) Oestrogen receptor-alpha and beta immunoreactivity in gonadotropin-releasing hormone neurons after ovariectomy and chronic exposure to oestradiol. J Neuroendocrinol 15 1164-1170... 

Interleukin 1 (IL-1) is produced mainly by activated monocytes-macropha-ges, and its principal action is to stimulate thymocytes. A pleiotropic cytokine, IL-1 induces the expression of a large diversity of cytokines such as IL-6, leukaemia inhibitory factor (LIF), and other proinflammatory molecules (Di-marello 1994). IL-1 and TNF-a carry out as part of their function increasing the expression of NF-/cB and JNK (c-Jun N-terminal kinase). The importance of IL-1 in OCS is demonstrated because the IL-1-receptor-deficient mouse is resistant to ovariectomy (OVX)-induced bone loss (Lorenzo et al. 1998). The importance in pathological bone loss is also illustrated by the fact that treatment with IL-1 receptor antagonist slows down bone erosion for patients affected with rheumatoid arthritis (Kwan et al. 2004). IL-1 increases osteoclast differentiation rather than mature osteoclast activity, and infusion of IL-1 into mice induces hypercalcemia and bone resorption. Finally, IL-1 and TNF-a... 

Lorenzo JA, Naprta A, Rao Y, Alander C, Glaccum M, Widmer M, Gronowicz G, Kalinowski J, Pilbeam CC (1998) Mice lacking the type I interleukin-1 receptor do not lose bone mass after ovariectomy. Endocrinology 139 3022-3025... 

Lasofoxifene is a SERM that also protects from bone loss, reduces cholesterol levels, and exerts a positive effect on bone strength in rats, specifically in male models (Ma et al. 2002). This compound is in the final stages of clinical development. Two other SERMs also in advanced phase III trials are bazedoxifene and arzoxifene, both with protective effects against ovariectomy-induced bone loss. Arzoxifene has shown both bone remodeling reduction with positive effects on bone quality as well as a reduction in cholesterol levels in oophorectomized rats (Biskobing2003). 

Ammann P, Bourrin S, Brunner F, Meyer JM, Clement-Lacroix P, Baron R, Gaillard M, Rizzoli R (2004) A new selective estrogen receptor modulator HMR-3339 fully corrects bone alterations induced by ovariectomy in adult rats. Bone 35 153-161... 

Arshad M, Sengupta S, Sharma S, Ghosh R, Sawlani V, Singh MM (2004) In vitro anti-resorptive activity and prevention of ovariectomy-induced osteoporosis in female Sprague-Dawley rats by ormeloxifene, a selective estrogen receptor modulator. J Steroid Biochem Mol Biol 91(l-2) 67-78... 

Chen HK, Ke E1Z, Jee WS, Ma YZ, Pirie CM, Simmons HA, et al. (1995) Droloxifene prevents ovariectomy-induced bone loss in tibiae and femora of aged female rats a dual absorptiometric and histomorphometric study. J Bone Miner Res 10 1256-1262... 

Takahashi, L. K. and Lisk, R. D. (1983) Organization and expression of agonistic and socio-sexual behavior in golden hamsters over the estrous cycle and after ovariectomy. Physiol. Behav. 31, 477-82. 

An investigation of G-8-PDH and 6-PGDH activities of mammary cancer tissues in rats showed a remarkable decrease following administration of dehydrotestosterone. Ovariectomy also resulted in a depression of enzyme activities of these tissues, which could be reversed by administration of 17 3-estradiol, an effect depending on dosage (R8). 

In rodents the most commonly studied female sexual behavior is the lordosis posture, in which the female remains immobile and concavely arches her back. Lordosis, usually in response to mounting, has been used as an index of female sexual receptivity. In addition, a variety of other measures such as elective proximity to a male have been used to index sexual proceptivity. Studies of these and related behaviors have shown that in rats ovarian secretions are essential for the expression of lordosis and can increase the expression of a variety of sociosexual behaviors (Pfaff, et al., 1994). Surgical removal of the ovary (ovariectomy) eliminates female sexual behavior in most rodents, and treatments with estrogen and progesterone can produce levels of sexual receptivity that closely resemble those seen in a gonadally-intact estrous female. 

The benzyl ester of hyaluronic acid (HYAFF 11) is a highly mucoadhesive polymer which can be processed into microspheres. Such microspheres containing salmon calcitonin were intravaginally administered to rats as a dosage form for the prevention of ovariectomy osteopenia [65]. In recent studies, HYAFF 11-salmon calcitonin microspheres were formulated as single-dose pessaries, resulting in sustained plasma concentrations of calcitonin [67]. 

Bonucci, E., Ballanti, P., Ramires, P.A., Richardson, J.L., and Benedetti, L.M., Prevention of ovariectomy osteopenia in rats after vaginal administration of Hyaff 11 microspheres containing salmon calcitonin, Calcif. Tissue Int., 56 274-279 (1995). 

Fig. 14 ZK-253 effects on tamoxifen-resistant breast cancer xenograft tumours. Estrogen-dependent MCF-7/TAM tumours were implanted on day 0 into one flank of 70 estrogen-and tamoxifen-supplemented nude mice. After tumours had reached approximately 25 mm in size (after about 22 days), mice were randomised into seven groups (10 mice each) three control groups (control tamoxifen, control vehicle or control ovariectomy without estradiol), and the fom treatment groups (ZK-703, ZK-253, raloxifene or fulves-trant) each at 10 mg/kg subcutaneously daily. Treatment was continued either until the end of the experiment or imtil tumoms reached a median of approximately 100 mm (larger tumours were observed in some mice). The tumours were then removed, snap frozen, and used for analysis of ER levels, a Xenograft tumour growth curves. Data are expressed as medians with interquartile ranges, b ERa levels. Data are expressed as mean with upper 95% Cl...

Ponnamperuma, R. M., Kirchhof, S. M., Trifiletti, L., and De Luca, L. M. (1999). Ovariectomy increases squamous metaplasia of uterine horns and survival SENCAR mice fed a vitamin A-deficient diet. Am. J. Clin. Nutr. 70, 502-508. 

Berk M, Kirchmann NH, Butkow N Dthium blocks 45Ca uptake into platelets in bipolar affective disorder and controls. Clin Neuropharmacol 19 48-51, 1996 Berman RM, Darnel AM, Anand A, et al Effect of pindolol in hastening response to fluoxetine in the treatment of major depression a double-blind placebo-controlled trial. Am J Psychiatry 154 37-43, 1997 Bernard M, Vergoni AV, Sandiini M, et al Influence of ovariectomy, estradiol and progesterone on the behavior of mice in an experimental model of depression. Physiol Behav 45 1067-1068, 1989... 

Ovariectomy caused a pronounced fall in the a-D-mannosidase activity of mouse uterus, and the normal level was restored by administration of estrone.28 Although the ovary is not particularly rich in a-D-man-nosidase, the greater proportion of the activity in cattle, pig, and human ovaries was found to be concentrated in the corpus luteum.14,28... 

Although the a-D-mannosidase activity of several different organs in mammals has been found to alter under a variety of conditions (see Section 11,1 p. 402),11,12-14,28,28 the most striking changes are those produced by sex hormones in the epididymis and uterus.26,28 In rats and mice, a-D-mannosidase activity in the epididymis increases with the age of the animal, up to maturity orchidectomy causes a dramatic fall in the enzyme activity of the adult tissue (up to 100-fold), but activity can be partially restored by the administration of testosterone. Ovariectomy results in a 10-fold fall in the activity of a-D-mannosidase in mouse uterus, and this is completely reversed by estrone. 

---