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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 66 (2000), S. 465-469 
    ISSN: 1432-0827
    Keywords: Key words: Bone histomorphometry — Estrogen metabolites — Bone formation — Bone resorption — Growth plate.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. 2-Methoxyestradiol (2-MeO-E2), a major metabolite of 17β-estradiol, may function as a physiological tumor suppressor and is being investigated for clinical applications. It has been reported to target rapidly dividing cells. We investigated the effects of 2-MeO-E2 on the growth plate of young rats because normal longitudinal bone growth requires rapid proliferation of cartilage and endothelial cells. Sexually mature (3-month-old) normal female rats were treated with 2-MeO-E2 (100 mg/kg/day) for 13 days and it was found to have no effect on uterine weight but reduced serum cholesterol. The estrogen metabolite had no effect on either cortical or cancellous bone. In contrast, 2-MeO-E2 dramatically reduced longitudinal bone growth rate at the proximal tibia from 55 ± 2 to 20 ± 2 μm/day (P 〈 0.001) and growth plate thickness from 153 ± 14 to 70 ± 6 μm (P 〈 0.001). The latter decrease was due to significant reductions in the height of both the proliferative (P 〈 0.001) and the hypertrophic (P 〈 0.001) zones. These results in normal female rats demonstrate that 2-MeO-E2 inhibited longitudinal bone growth but had no effect on either radial bone growth or cancellous bone turnover. 2-MeO-E2 was shown by these studies to have the ability to discriminate between bone and cartilage, as well as between reproductive and nonreproductive estrogen-target tissues. Thus, 2-MeO-E2 is a naturally produced estrogen metabolite that demonstrates unique tissue selectivity.
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  • 2
    ISSN: 1432-0827
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. Leukemia inhibitory factor (LIF) is a single-chain polypeptide that previously was shown in mice to produce hypercalcemia and influence skeletal growth and turnover. We performed dose-response studies to determine if LIF alters the serum calcium or histomorphometry of the tibia in growing male rats. Forty animals were divided into five groups of eight animals each. Recombinant human LIF, 0.01, 0.1, 1, or 10 μg/100 g body wt, or vehicle was administered daily S.C. for 3 weeks. Compared with controls it was found that LIF increased mean serum calcium at the two highest doses (11.4 ± 0.1 versus 10.8 ± 0.1 mg/dl, P= 0.0005 by one-way analysis of variance (ANOVA) but did not alter static or dynamic measurements of histomorphometry or length of the tibia. We conclude that in growing rats, high systemic concentrations of LIF result in hypercalcemia with no changes in bone turnover.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 60 (1997), S. 37 -42 
    ISSN: 1432-0827
    Keywords: Key words: Estrogen — Male rats — Bone histomorphometry — Bone formation — Bone resorption.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. The short-term effects of estrogen at a single high dose (4 mg/kg body weight/day for 14 days) were determined on tibiae in the normal (noncastrate) growing male rat. In cortical periosteal bone, at a middiaphyseal site devoid of resorbing activity, estrogen suppressed periosteal bone formation and apposition rates, resulting in a smaller cross-sectional area. In middiaphyseal endocortical bone, estrogen had no effect on apposition and formation rates and, because medullary area was unchanged, probably had no effect on endocortical bone resorption. In the proximal tibial metaphysis, estrogen greatly suppressed longitudinal growth rate. In a site within the metaphysis adjusted for the effects of growth, cancellous mineral apposition was greatly reduced by the hormone. Estrogen-treated rats retained more of a fluorochrome label deposited in cancellous bone at the beginning of the study than vehicle-treated animals, indicating a reduced net bone loss. As a result of the lowered resorption induced by estrogen, cancellous bone mass (area and perimeter) were both significantly higher in estrogen-treated rats. No evidence was found for an anabolic action of the hormone in the male rat; indeed, estrogen reduced indices of bone formation.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 66 (2000), S. 461-464 
    ISSN: 1432-0827
    Keywords: Key words: Bone histomorphometry — Orchiectomy — Estrogens — Sexual dimorphism — Androgens.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. Estrogens have profound effects on the processes of bone formation and turnover in females. The physiological role of this class of hormones on bone metabolism in males is less certain. The purpose of this study was to determine the effect of the high affinity estrogen receptor antagonist ICI 182,780 on tibial growth in normal male rats. The effects of ICI 182,780 on growing male rats were compared to orchiectomy, which prevents the synthesis of estrogens as well as androgens. Neither orchiectomy nor ICI 182,780 had an effect on body weight gained. Orchiectomy decreased longitudinal bone growth at the proximal tibial metaphysis and radial bone growth at the tibia-fibula synostosis. In contrast, ICI 182,780 had no effect on either endochondral or intramembranous bone growth. These findings suggest that androgens are more important than estrogens in determining peak bone mass in male rats.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 67 (2000), S. 47-52 
    ISSN: 1432-0827
    Keywords: Key words: Bone formation — Bone resorption — Osteoporosis — Bone growth — Ovariectomy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. The present study was performed to evaluate possible interactions between estrogen and progesterone on peak cancellous bone mass. Ovariectomized (OVX) growing rats were treated with 17β-estradiol (4.8 μg/day), progesterone (4.8 mg/day), a combination of the two sex steroids, or with vehicle for 14 days beginning 7 days after OVX. The tibiae were removed for histomorphometric analysis of the proximal metaphysis. OVX and growth each resulted in net resorption of cancellous bone at a sampling site adjusted for longitudinal bone growth. Estradiol and progesterone treatment each antagonized bone loss by inhibiting the decrease in trabecular number. Estradiol increased but progesterone had no effect on trabecular thickness. Progesterone did not influence either osteoclast number or the resorption of the pretreatment fluorochrome label. Estradiol reduced osteoclast number and inhibited label resorption, the latter change being accentuated by combination treatment. Estradiol reduced and progesterone enhanced the mineral apposition and bone formation rates. The results indicate that estradiol and progesterone have independent activities on cancellous bone turnover during growth. Whereas estradiol reduced bone turnover, progesterone had a stimulatory effect on bone formation. These findings suggest that progesterone has a role in establishing and maintaining peak cancellous bone volume during growth.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 56 (1995), S. 311-315 
    ISSN: 1432-0827
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Prednisone inhibits bone formation and causes bone loss. To investigate possible mechanisms and sites, the effects of sham operation, ovariectomy, and prednisone were determined on bone and mineral metabolism in 7-week-old growing female rats. Forty animals were divided into groups of 10 each. Sham operation and ovariectomy were performed. One week later, pellets containing 5 mg prednisone or drug free were implanted S.C. at the back of the neck. Four weeks later, animals were sacrificed and tibiae were removed for histomorphometric analysis of the middiaphysis and proximal metaphysis. In both sham-operated and ovariectomized rats, prednisone (1) reduced weight gain (P〈0.02) and did not alter uterine weight; (2) lowered serum magnesium (Mg) (P〈0.001) and did not change serum calcium (Ca), phosphate (P), 25-hydroxyvitamin D (25OHD), or 1,25-dihydroxyvitamin D [1,25(OH)2D]; (3) produced striking increases in calcified cartilage, reduced cross-sectional area (P〈0.05) and cortical area (P〈0.01) and did not change medullary area of the tibial diaphysis; (4) lowered periosteal and endocortical bone formation and apposition rates; and (5) increased mean cancellous bone area (P〈0.05) and cancellous bone perimeter (P〈0.01) of the tibial metaphysis. In both control and prednisone-treated rats, ovariectomy (1) reduced uterine weight (P〈0.001); (2) did not change serum Ca, P, Mg, 25OHD, or 1,25(OH)2D; (3) did not change mean cross-sectional, medullary, or cortical areas; (4) increased periosteal bone formation and apposition rates (P〈0.01) and did not alter endosteal bone formation and apposition rates, and (5) decreased cancellous bone area (P〈0.01) and cancellous bone perimeter (P〈0.01). Thus, in short-term studies, prednisone increased calcified cartilage and inhibited the formation of cortical bone at periosteal and endosteal surfaces and reduced cortical bone of the tibia in both sham-operated and ovariectomized, rapidly growing animals.
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  • 7
    ISSN: 1432-0827
    Keywords: Key words: Estrogen — Growth hormone — Ovariectomy — Hypophysectomy — Rat bone histomorphometry.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. Pituitary hormones are recognized as critical to longitudinal growth, but their role in the radial growth of bone and in maintaining cancellous bone balance are less clear. This investigation examines the histomorphometric effects of hypophysectomy (Hx) and ovariectomy (OVX) and the subsequent replacement of growth hormone (GH) and estrogen (E), in order to determine the effects and possible interactions between these two hormones on cortical and cancellous bone growth and turnover. The replacement of estrogen is of interest since Hx results in both pituitary and gonadal hormone insufficiencies, with the latter being caused by the Hx-associated reduction in follicle stimulating hormone (FSH). All hypophysectomized animals received daily supplements of hydrocortisone (500 μg/kg) and l-thyroxine (10 μg/kg), whereas intact animals received daily saline injections. One week following surgery, hypophysectomized animals received either daily injections of low-dose 17 β-estradiol (4.8 μg/kg s.c.), 3 X/d recombinant human GH (2 U/kg s.c.), both, or saline for a period of two weeks. Flurochromes were administered at weekly intervals to label bone matrix undergoing mineralization. Whereas Hx resulted in reductions in body weight, uterine weight, and tibial length, OVX significantly increased body weight and tibial length, while reducing uterine weight. The combination of OVX and Hx resulted in values similar to Hx alone. Treatment with GH normalized body weight and bone length, while not affecting uterine weight in hypophysectomized animals. Estrogen increased uterine weight, while not impacting longitudinal bone growth and reduced body weight. Hypophysectomy diminished tibial cortical bone area through reductions in both mineral appositional rate (MAR) and bone formation rate (BFR). While E had no effect, GH increased both MAR and BFR, though not to sham-operated (control) levels. Hypophysectomy reduced proximal tibial trabecular number and cancellous bone area, and increased trabecular separation. Both GH and E reduced cancellous osteopenia, although employing different mechanisms. GH reduced the decrease in trabecular thickness, whereas E reduced the decrease in trabecular number and the increase in trabecular separation. Hypophysectomy reduced both Tb.MAR and Tb.BFR while treatment with GH enhanced them. This investigation has shown that Hx and GH have a dramatic impact on selected static and dynamic indices of rat cortical and cancellous histomorphometry. Furthermore, the mechanisms of action of GH and E differ, and suggest that some of the skeletal changes associated with Hx are caused by deficiencies in estrogen as well as deficiencies in growth hormone.
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  • 8
    ISSN: 1432-0827
    Keywords: Mineral metabolism ; Parathyroid extract ; Thyroparathyroidectomy ; 25-Hydroxyvitamin D3 ; 1,25-Dihydroxyvitamin D3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Thyroparathyroidectomized rats fed a diet containing 1.2% calcium, 0.55% phosphorus maintain normal serum levels of these ions. Treatment of such rats with parathyroid extract (PTE; 20 U/100 g twice daily; 10 days) has no statistically significant effect on rates of bone formation, matrix apposition, or osteoid maturation. Significant decreases in osteoid width and mineralizing front width, as well as a 60% increase in the rate of initial mineralization were observed in the PTE-treated group. Conversion of3H-25-hydroxyvitamin D3 to3H-1,25-dihydroxyvitamin D3 was 4-fold higher in the PTE-treated group than in the untreated animals. Increased formation of 1,25-dihydroxyvitamin D3 in response to treatment with PTE may play a major role in correcting the mineralizing defect resulting from thyroparathyroidectomy.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Bulletin of environmental contamination and toxicology 19 (1978), S. 139-142 
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
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  • 10
    Publication Date: 1981-05-01
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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