Enhanced trabecular-bone calcium deposition in female rats with a high physiological dose of prolactin diminishes after ovariectomy

2006 ◽  
Vol 84 (10) ◽  
pp. 993-1002 ◽  
Author(s):  
Supaporn Puntheeranurak ◽  
Narattaphol Charoenphandhu ◽  
Nateetip Krishnamra

Although an increase in trabecular-bone calcium deposition has been shown to be regulated by prolactin during lactation, the physiological significance of prolactin in bone calcium metabolism in nonlactating rats remains unclear. This investigation sought to demonstrate the effects of endogenous prolactin and a high physiological dose of exogenous prolactin on bone turnover and bone calcium deposition in normal female rats, using the 45Ca-labeling technique. Our results showed that suppression of endogenous prolactin with 6 mg/kg bromocriptine for 15 days significantly enhanced bone formation, but not bone resorption, in primarily trabecular sites, resulting in a significant increase in calcium deposition in the sternum and vertebrae, from –0.20 ± 0.07 to 0.40 ± 0.09 (p < 0.05) and –0.07 ± 0.11 to 0.34 ± 0.06 (p < 0.05) mmol Ca·(g dry mass)–1, respectively. Similarly, 2.5 mg/kg prolactin, a high physiological dose, increased sternal and vertebral calcium deposition, from –0.20 ± 0.07 to 0.24 ± 0.09 (p < 0.05) and –0.07 ± 0.11 to 0.25 ± 0.18 (p < 0.05) mmol Ca·(g dry mass)–1, respectively, by increasing bone formation more than bone resorption. However, as expected, prolactin had no effect on the tibia or femur, which are primarily cortical sites. Because several actions of prolactin have been known to be estradiol-dependent, we further investigated the dependence of prolactin action on 17β-estradiol. We found that 2.5 mg/kg prolactin did not increase sternal calcium deposition in ovariectomized rats. However, 10 µg/kg 17β-estradiol supplementation restored the action of prolactin. Ovariectomized rats given 17β-estradiol plus prolactin also manifested slightly but significantly higher sternal total calcium content than sham-operated rats, (4.58 ± 0.12 vs. 4.36 ± 0.11 mmol Ca·(g dry mass)–1 (p < 0.05)). We concluded that a high physiological dose of prolactin promoted calcium deposition in primarily trabecular sites of nonlactating rats. This effect was diminished after ovariectomy. In addition, we showed that basal endogenous prolactin played a role in the maintenance of normal trabecular-bone turnover.

1986 ◽  
Vol 251 (4) ◽  
pp. E400-E406 ◽  
Author(s):  
P. J. Marie ◽  
L. Cancela ◽  
N. Le Boulch ◽  
L. Miravet

The effects of pregnancy and lactation on endosteal bone formation and resorption were evaluated in vitamin D-depleted (-D) and vitamin D-repleted (+D) rats. Pregnancy induced a marked stimulation of osteoclastic bone resorption and of static and dynamic parameters of bone formation and mineralization. Bone resorption increased independently of vitamin D status and did not correlate with plasma 1,25-dihydroxyvitamin D3 [1,25(OH)2D] levels, but it was associated with increased plasma immunoreactive parathyroid hormone (iPTH) concentrations. Stimulation of the endosteal bone formation rate was mainly impaired in D-depleted rats, resulting in trabecular bone loss, which, in -D mother rats, was associated with decreased bone ash and total bone calcium. Lactation further stimulated bone resorption and reduced the trabecular bone volume; ash weight and bone calcium content were also decreased independently of the vitamin D status and changes in plasma iPTH levels. In presence of vitamin D, the bone formation rate increased fourfold during lactation but was unchanged in -D lactating rats. During lactation, vitamin D-depleted rats lost twofold more calcified bone than +D rats because of impaired mineralization. Thus, the present study shows that both the endosteal bone resorption and formation are stimulated by pregnancy and lactation and that vitamin D is required for normal bone mineralization during the reproductive period.


1998 ◽  
Vol 12 (1) ◽  
pp. 76-81 ◽  
Author(s):  
T. Sasaki ◽  
N.S. Ramamurthy ◽  
L.M. Golub

The effect of a new non-antimicrobial analog of tetracycline (CMT-8) on bone loss in ovariectomized (OVX) rats was examined. Three-month-old female rats were ovariectomized, and one week later, were distributed into 3 groups: sham-operated non-OVX controls, vehicle-treated OVX controls, and CMT-8-treated OVX rats. After 145 days of daily CMT-8 administration, the intact femurs were dissected and examined by several histological and histomorphometric techniques. OVX significantly (p < 0.01) decreased trabecular bone volume by 53.4% in the metaphyses compared with sham-operated controls. CMT-8 therapy produced a significant (p < 0.05) inhibition of trabecular bone loss and also induced bone formation in the OVX rats. Of interest, the newly synthesized bone in the CMT-treated OVX rats was found to increase the "connectivity" of the trabecular "struts" by bridging the adjacent longitudinal bone trabeculae, forming dense, platelike bone trabeculae. These results strongly suggest that long-term CMT-8 therapy effectively inhibits bone loss after OVX, not only by inhibiting bone resorption but also by inducing new bone formation in the trabecular areas of long bones.


2018 ◽  
Vol 36 (1) ◽  
pp. 1
Author(s):  
Hartiningsih Hartiningsih ◽  
Devita Anggraeni

Calcitriol supplementation in ovariectomized rats decreased bone resorption and increased bone formation, however, it depend on dose. The objective of the research was to study the response of femur bone in osteoporosis rats consuming calcitriol. Thirty female Wistar rats at 8 weeks of age were randomly divided into six groups (sham operated rats as normal control rats/group N and NK, ovariectomized control rats/group Ov and OvK, ovariectomized rats/group OvDand OvE) of five each. All rats were fed standard diet for 8 weeks. At 16 weeks  of age, group N and Ov  were euthanized, the right femur were taken for histopathological  examination. Group NK and OvK were fed a standard diet, group OvD was fed a standard diet +40ng calcitriol;  and group OvE was fed a standard diet+25µg ethynil ethyl estradiol. Treatments were done for six weeks. At the end of study, blood samples were taken from plexus orbitalis medialis for estrogen analysis. All rats were euthanized using ketamine10% and xylazine 2%. Right femur was taken for histopathological examination  using hematoxylin and eosin stain, and immunohistochemistry using monoclonal antibody anti TRAP5b which was detected with streptavidin-biotin.         The results showed that estradiol level of the rats in group OvD was not significantly different compared with the rats in OvK group, however, it was significanly lower compared to the rats in group OvE. Histopathologic figure of right distal femur metaphysis in group OvD was shown lesser adipocyte in the bone marrow and more trabecular bone speculum compared to group  OvK, however, there was more adipocyte in the bone marrow and lesser trabecular bone speculum compared to group OvE. Immunohistochemistry of distal femur metaphysis in group OvD and OvE were revealed tartrate resistant alkaline phosphatase 5b (TRAP5b) expression in trabecular bone, which was located in bone marrow space and trabecular speculum surface as well. Based on the results, it can be concluded that calcitriol 40ng/day supplementation in osteoporosis rats for 6 weeks decreased bone resorption and increased bone formation distal femur metaphysis.


Endocrinology ◽  
1991 ◽  
Vol 128 (1) ◽  
pp. 408-412 ◽  
Author(s):  
J. H. TOBIAS ◽  
J. CHOW ◽  
K. W. COLSTON ◽  
T. J. CHAMBERS

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Rafaela G. Feresin ◽  
Sarah A. Johnson ◽  
Marcus L. Elam ◽  
Jeong-Su Kim ◽  
Dania A. Khalil ◽  
...  

The present study examined the dose-dependent effect of vitamin E in reversing bone loss in ovariectomized (Ovx) rats. Sprague-Dawley rats were either Sham-operated (Sham) or Ovx and fed control diet for 120 days to lose bone. Subsequently, rats were divided into 5 groups (n=12/group): Sham, Ovx-control, low dose (Ovx + 300 mg/kg diet; LD), medium dose (Ovx + 525 mg/kg diet; MD), and high dose (Ovx + 750 mg/kg diet; HD) of vitamin E and sacrificed after 100 days. Animals receiving MD and HD of vitamin E had increased serum alkaline phosphatase compared to the Ovx-control group. Bone histomorphometry analysis indicated a decrease in bone resorption as well as increased bone formation and mineralization in the Ovx groups supplemented with MD and HD of vitamin E. Microcomputed tomography findings indicated no effects of vitamin E on trabecular bone of fifth lumbar vertebrae. Animals receiving HD of vitamin E had enhanced fourth lumbar vertebra quality as evidenced by improved ultimate and yield load and stress when compared to Ovx-control group. These findings demonstrate that vitamin E improves bone quality, attenuates bone resorption, and enhances the rate of bone formation while being unable to restore bone density and trabecular bone structure.


Bone ◽  
2015 ◽  
Vol 81 ◽  
pp. 449-458 ◽  
Author(s):  
Sadaoki Sakai ◽  
Satoshi Takeda ◽  
Masanori Sugimoto ◽  
Masaru Shimizu ◽  
Yasushi Shimonaka ◽  
...  

2018 ◽  
Vol 238 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Thomas Funck-Brentano ◽  
Karin H Nilsson ◽  
Robert Brommage ◽  
Petra Henning ◽  
Ulf H Lerner ◽  
...  

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.


2001 ◽  
Vol 280 (1) ◽  
pp. L88-L97 ◽  
Author(s):  
Thomas C. Resta ◽  
Nancy L. Kanagy ◽  
Benjimen R. Walker

Female rats develop less severe pulmonary hypertension (PH) in response to chronic hypoxia compared with males, thus implicating a potential role for ovarian hormones in mediating this gender difference. Considering that estrogen upregulates endothelial nitric oxide (NO) synthase (eNOS) in systemic vascular tissue, we hypothesized that estrogen inhibits hypoxic PH by increasing eNOS expression and activity. To test this hypothesis, we examined responses to the endothelium-derived NO-dependent dilator ionomycin and the NO donors S-nitroso- N-acetylpenicillamine and spermine NONOate in U-46619-constricted, isolated, saline-perfused lungs from the following groups: 1) normoxic rats with intact ovaries, 2) chronic hypoxic (CH) rats with intact ovaries, 3) CH ovariectomized rats given 17β-estradiol (E2β), and 4) CH ovariectomized rats given vehicle. Additional experiments assessed pulmonary eNOS levels in each group by Western blotting. Our findings indicate that E2β attenuated chronic hypoxia-induced right ventricular hypertrophy, pulmonary arterial remodeling, and polycythemia. Furthermore, although CH augmented vasodilatory responsiveness to ionomycin and increased pulmonary eNOS expression, these responses were not potentiated by E2β. Finally, responses to S-nitroso- N-acetylpenicillamine and spermine NONOate were similarly attenuated in all CH groups compared with normoxic control groups. We conclude that the inhibitory influence of E2β on chronic hypoxia-induced PH is not associated with increased eNOS expression or activity.


1977 ◽  
Vol 55 (2) ◽  
pp. 188-192
Author(s):  
Padmaja N. Kulkarni ◽  
Alan A. Simpson ◽  
William H. Moger

The effect of androgens on pituitary response to luteinizing-hormone-releasing hormone (LHRH) and their ability to modify effects of 17β-estradiol (E2) on pituitary responsiveness to LHRH were tested in ovariectomized rats maintained on a daily dose of 0.25 μg estradiol benzoate per rat for 6 d before androgen administration.Testosterone propionate (TP) (4, 40, 400, or 4000 μg per rat), administered 24 h before LHRH (500 ng per rat), had no significant effect on luteinizing hormone (LH) or follicle-stimulating hormone (FSH) response. Similar doses of dihydrotestosterone (DHT) did not significantly alter the LH response but significantly suppressed the FSH response. Even the lowest dose completely blocked the FSH response to LHRH. TP in combination with 4 or 400 μg of E2 suppressed the stimulatory effect of E2 on both LH and FSH response to LHRH in a dose-related manner. DHT and E2 in combination affected LH response inconsistently, whereas their ratio determined FSH response; there was pronounced inhibition of FSH response in rats given high doses of DHT combined with low doses of E2; DHT inhibition of FSH response in animals receiving 4 μg of DHT with 400 μg E2 was partially overcome by the stimulatory effect of E2. Our results indicate that TP and DHT affect LH and FSH response to LHRH differently. The ratio of androgen to estrogen is important in determining the response to LHRH.


2004 ◽  
Vol 19 (7) ◽  
pp. 1144-1153 ◽  
Author(s):  
Sophie Schaller ◽  
Kim Henriksen ◽  
Christina Sveigaard ◽  
Anne-Marie Heegaard ◽  
Nathalie Hélix ◽  
...  

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