Bone phenotype of the aromatase deficient mouse

Öz, Orhan K.; Hirasawa, Gen; Lawson, J. W. Randolph; Nanu, L; Constantinescu, A; Antich, Peter P.; Mason, Ralph P.; Tsyganov, E.; Parkey, Robert W.; Zerwekh, Joseph E.; Simpson, Evan R.

doi:10.1016/s0960-0760(01)00130-3

Cited by 85 publications

(25 citation statements)

References 21 publications

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“…In contrast, the other knockout mouse models either had normal or decreased growth of the femur and/or tibia [29,30,31]. One must bear in mind that in our study, exemestane was administered during a short time frame, whereas inborn genetic mutations in knockout mice and human patients with estrogen deficiency or resistance can influence growth during all stages of life, which may explain the differences in growth characteristics.…”

Section: Discussionmentioning

confidence: 89%

“…Rats tend to respond in a similar fashion as humans to estrogen, with estrogen deficiency stimulating growth and estrogen treatment causing growth arrest [27]. In contrast, estrogen receptor (α/β/αβ) and aromatase knockout mice show a normal adult length [28,29,30,31,32], indicating that hormonal regulation of growth in mice is distinctly different than in humans and rats. We therefore feel that the rat is the most appropriate of the available animal models for in vivo studies on the impact of chemically induced aromatase deficiency.…”

Section: Discussionmentioning

confidence: 99%

“…An increased body weight gain was also observed in female ERαKO and ERαβKO mice, and female ArKO mice [29,30,31,37], corresponding with an increased deposition of intra-abdominal adipose tissue, high leptin and cholesterol levels, and hyperinsulinism [38]. An elevated BMI has not been described in female patients with aromatase deficiency, but this is probably due to the fact that they have received estrogen treatment.…”

Section: Discussionmentioning

confidence: 99%

“…In female ERαKO, ERβKO, ERαβKO and ArKO mice, adult length was found to be normal compared to wild-type mice [28,29,30,31,32]. However, the ERβKO mouse has a tendency to slightly increased growth during the postpubertal phase [31], whereas female ArKO mice show an increased length gain peripubertally [29,30]. E100 treatment resulted in a marginal increase of the length of the tibia (not significant).…”

Section: Discussionmentioning

confidence: 99%

“…Loss of bone tissue is a sign of osteopenia, generally considered as the stadium preceding osteoporosis. Similarly, ArKO mice were found to have a decreased peak BMD, prominent osteopenia on plain film radiographs and decreased trabecular volume and thickness [29,30]. A low BMD was also found in ERβKO and ERαβKO mice [31].…”

Section: Discussionmentioning

confidence: 99%

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Marginal Growth Increase, Altered Bone Quality and Polycystic Ovaries in Female Prepubertal Rats after Treatment with the Aromatase Inhibitor Exemestane

Gool

Wit²,

Schutter³

et al. 2010

Horm Res Paediatr

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Background: Aromatase inhibition has been proposed as a potential approach for growth enhancement in children with short stature, but detailed animal studies are lacking. Aim: To assess the effect and potential adverse effects of aromatase inhibition on growth in female rats. Methods: Prepubertal Wistar rats received intramuscular injections with placebo or the aromatase inhibitor exemestane at a dose of 10, 30 or 100 mg/kg/week (E10, E30, E100) for 3 weeks. A control group was ovariectomized (OVX). Weight and length gain, tibia and femur length, growth plate width, organ weights, insulin-like growth factor I (IGF-I) levels, and histology of the ovaries, uterus and brain were analyzed. X-ray microtomography of femora was performed. Results: E100 significantly increased weight gain and growth plate width, but less prominently than OVX. Trabecular number and thickness were decreased in E100 and OVX in the metaphysis and epiphysis. E100 significantly decreased ovarian weight and multiple cysts were seen upon histological evaluation. No significant effects were found on IGF-I levels and brain morphology in E100. E10 and E30 had no effects on growth. Conclusion: A high dose of exemestane marginally increases axial and appendicular growth in female rats, at the expense of osteopenia and polycystic ovaries.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Marginal Growth Increase, Altered Bone Quality and Polycystic Ovaries in Female Prepubertal Rats after Treatment with the Aromatase Inhibitor Exemestane

Gool

Wit²,

Schutter³

et al. 2010

Horm Res Paediatr

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GPR30 deficiency causes increased bone mass, mineralization, and growth plate proliferative activity in male mice

Ford

Hajibeigi

Long

et al. 2010

Journal of Bone and Mineral Research

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Estrogen regulation of the male skeleton was first clearly demonstrated in patients with aromatase deficiency or a mutation in the ERα gene. Estrogen action on the skeleton is thought to occur mainly through the action of the nuclear receptors ERα and ERβ. Recently, in vitro studies have shown that the G protein–coupled receptor GPR30 is a functional estrogen receptor (ER). GPR30-deficient mouse models have been generated to study the in vivo function of this protein; however, its in vivo role in the male skeleton remains underexplored. We have characterized size, body composition, and bone mass in adult male Gpr30 knockout (KO) mice and their wild-type (WT) littermates. Gpr30 KO mice weighed more and had greater nasal-anal length (p < .001). Both lean mass and percent body fat were increased in the KO mice. Femur length was greater in Gpr30 KO mice, as was whole-body, spine, and femoral areal bone mineral density (p < .01). Gpr30 KO mice showed increased trabecular bone volume (p < .01) and cortical thickness (p < .001). Mineralized surface was increased in Gpr30 KO mice (p < .05). Bromodeoxyuridine (BrdU) labeling showed greater proliferation in the growth plate of Gpr30 KO mice (p < .05). Under osteogenic culture conditions, Gpr30 KO femoral bone marrow cells produced fewer alkaline phosphatase–positive colonies in early differentiating osteoblast cultures but showed increased mineralized nodule deposition in mature osteoblast cultures. Serum insulin-like growth factor 1 (IGF-1) levels were not different. These data suggest that in male mice, GPR30 action contributes to regulation of bone mass, size, and microarchitecture by a mechanism that does not require changes in circulating IGF-1. © 2011 American Society for Bone and Mineral Research.

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Influence of Aromatase Inhibition on the Bone-Protective Effects of Testosterone

Beck

Yarrow

Beggs

et al. 2014

Journal of Bone and Mineral Research

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The influence of the aromatase enzyme in androgen-induced bone maintenance after skeletal maturity remains somewhat unclear. Our purpose was to determine whether aromatase activity is essential to androgen-induced bone maintenance. Ten-month-old male Fisher 344 rats (n = 73) were randomly assigned to receive Sham surgery, orchiectomy (ORX), ORX + anastrozole (AN; aromatase inhibitor), ORX + testosterone-enanthate (TE, 7.0 mg/wk), ORX + TE + AN, ORX + trenbolone-enanthate (TREN; nonaromatizable, nonestrogenic testosterone analogue; 1.0 mg/wk), or ORX + TREN + AN. ORX animals exhibited histomorphometric indices of high-turnover osteopenia and reduced cancellous bone volume compared with Shams. Both TE and TREN administration suppressed cancellous bone turnover similarly and fully prevented ORX-induced cancellous bone loss. TE- and TREN-treated animals also exhibited greater femoral neck shear strength than ORX animals. AN co-administration slightly inhibited the suppression of bone resorption in TE-treated animals but did not alter TE-induced suppression of bone formation or the osteogenic effects of this androgen. In TREN-treated animals, AN co-administration produced no discernible effects on cancellous bone turnover or bone volume. ORX animals also exhibited reduced levator ani/bulbocavernosus (LABC) muscle mass and elevated visceral adiposity. In contrast, TE and TREN produced potent myotrophic effects in the LABC muscle and maintained fat mass at the level of Shams. AN co-administration did not alter androgen-induced effects on muscle or fat. In conclusion, androgens are able to induce direct effects on musculoskeletal and adipose tissue, independent of aromatase activity.

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Bone phenotype of the aromatase deficient mouse

Cited by 85 publications

References 21 publications

Marginal Growth Increase, Altered Bone Quality and Polycystic Ovaries in Female Prepubertal Rats after Treatment with the Aromatase Inhibitor Exemestane

Marginal Growth Increase, Altered Bone Quality and Polycystic Ovaries in Female Prepubertal Rats after Treatment with the Aromatase Inhibitor Exemestane

GPR30 deficiency causes increased bone mass, mineralization, and growth plate proliferative activity in male mice

Influence of Aromatase Inhibition on the Bone-Protective Effects of Testosterone

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