scholarly journals Role of estrogen receptor signaling in skeletal response to leptin in female ob/ob mice

2017 ◽  
Vol 233 (3) ◽  
pp. 357-367 ◽  
Author(s):  
Russell T Turner ◽  
Kenneth A Philbrick ◽  
Amida F Kuah ◽  
Adam J Branscum ◽  
Urszula T Iwaniec
Keyword(s):  
Estrogen Receptor ◽  
Cancellous Bone ◽  
Bone Growth ◽  
Volume Fraction ◽  
Gonadal Hormones ◽  
Uterine Weight ◽  
Bone Formation Rate ◽  
Longitudinal Bone Growth ◽  
Gonadal Dysfunction

Leptin, critical in regulation of energy metabolism, is also important for normal bone growth, maturation and turnover. Compared to wild type (WT) mice, bone mass is lower in leptin-deficient ob/ob mice. Osteopenia in growing ob/ob mice is due to decreased bone accrual, and is associated with reduced longitudinal bone growth, impaired cancellous bone maturation and increased marrow adipose tissue (MAT). However, leptin deficiency also results in gonadal dysfunction, disrupting production of gonadal hormones which regulate bone growth and turnover. The present study evaluated the role of increased estrogen in mediating the effects of leptin on bone in ob/ob mice. Three-month-old female ob/ob mice were randomized into one of the 3 groups: (1) ob/ob + vehicle (veh), (2) ob/ob + leptin (leptin) or (3) ob/ob + leptin and the potent estrogen receptor antagonist ICI 182,780 (leptin + ICI). Age-matched WT mice received vehicle. Leptin (40 µg/mouse, daily) and ICI (10 µg/mouse, 2×/week) were administered by subcutaneous injection for 1 month and bone analyzed by X-ray absorptiometry, microcomputed tomography and static and dynamic histomorphometry. Uterine weight did not differ between ob/ob mice and ob/ob mice receiving leptin + ICI, indicating that ICI successfully blocked the uterine response to leptin-induced increases in estrogen levels. Compared to leptin-treated ob/ob mice, ob/ob mice receiving leptin + ICI had lower uterine weight; did not differ in weight loss, MAT or bone formation rate; and had higher longitudinal bone growth rate and cancellous bone volume fraction. We conclude that increased estrogen signaling following leptin treatment is dispensable for the positive actions of leptin on bone and may attenuate leptin-induced bone growth.

scholarly journals The role of estrogen receptor-α and its activation function-1 for growth plate closure in female mice

2012 ◽  
Vol 302 (11) ◽  
pp. E1381-E1389 ◽  
Author(s):  
A. E. Börjesson ◽  
S. H. Windahl ◽  
E. Karimian ◽  
E. E. Eriksson ◽  
M. K. Lagerquist ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Growth Plate ◽  
Bone Growth ◽  
High Dose ◽  
Plate Height ◽  
Chondrocyte Proliferation ◽  
Growth Plates ◽  
Longitudinal Bone Growth ◽  
Female Mice

High estradiol levels in late puberty induce growth plate closure and thereby cessation of growth in humans. In mice, the growth plates do not fuse after sexual maturation, but old mice display reduced longitudinal bone growth and high-dose estradiol treatment induces growth plate closure. Estrogen receptor (ER)-α stimulates gene transcription via two activation functions (AFs), AF-1 and AF-2. To evaluate the role of ERα and its AF-1 for age-dependent reduction in longitudinal bone growth and growth plate closure, female mice with inactivation of ERα (ERα−/−) or ERαAF-1 (ERαAF-10) were evaluated. Old (16- to 19-mo-old) female ERα−/− mice showed continued substantial longitudinal bone growth, resulting in longer bones (tibia: +8.3%, P < 0.01) associated with increased growth plate height (+18%, P < 0.05) compared with wild-type (WT) mice. In contrast, the longitudinal bone growth ceased in old ERαAF-10 mice (tibia: −4.9%, P < 0.01). Importantly, the proximal tibial growth plates were closed in all old ERαAF-10 mice while they were open in all WT mice. Growth plate closure was associated with a significantly altered balance between chondrocyte proliferation and apoptosis in the growth plate. In conclusion, old female ERα−/− mice display a prolonged and enhanced longitudinal bone growth associated with increased growth plate height, resembling the growth phenotype of patients with inactivating mutations in ERα or aromatase. In contrast, ERαAF-1 deletion results in a hyperactive ERα, altering the chondrocyte proliferation/apoptosis balance, leading to growth plate closure. This suggests that growth plate closure is induced by functions of ERα that do not require AF-1 and that ERαAF-1 opposes growth plate closure.

The role of estrogen receptor α in growth plate cartilage for longitudinal bone growth

2010 ◽  
Vol 25 (12) ◽  
pp. 2690-2700 ◽  
Author(s):  
Anna E Börjesson ◽  
Marie K Lagerquist ◽  
Chen Liu ◽  
Ruijin Shao ◽  
Sara H Windahl ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Growth Plate ◽  
Bone Growth ◽  
Estrogen Receptor Α ◽  
Longitudinal Bone Growth ◽  
Growth Plate Cartilage

scholarly journals Estrogen receptor specificity in the regulation of the skeleton in female mice

2001 ◽  
Vol 171 (2) ◽  
pp. 229-236 ◽  
Author(s):  
MK Lindberg ◽  
SL Alatalo ◽  
JM Halleen ◽  
S Mohan ◽  
JA Gustafsson ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Bone Growth ◽  
Fat Content ◽  
Mineral Density ◽  
Trabecular Bone Mineral Density ◽  
Longitudinal Bone Growth ◽  
Female Mice ◽  
Opposing Effects ◽  
Er Alpha

There are two known estrogen receptors, estrogen receptor-alpha (ER alpha) and estrogen receptor-beta (ER beta), which may mediate the actions of estrogen. The aim of the present study was to compare fat content, skeletal growth and adult bone metabolism in female mice lacking ER alpha (ERKO), ER beta (BERKO) or both ERs (DERKO). We demonstrate that endogenous estrogens decrease the fat content in female mice via ER alpha and not ER beta. Interestingly, the longitudinal bone growth was decreased in ERKO, increased in BERKO, but was intermediate in DERKO females, demonstrating that ER alpha and ER beta exert opposing effects in the regulation of longitudinal bone growth. The effects on longitudinal bone growth were correlated with similar effects on serum levels of IGF-I. A complex regulation of the trabecular bone mineral density (BMD), probably caused by a disturbed feedback regulation of estrogen and testosterone, was observed in female ER-inactivated mice. Nevertheless, a partial functional redundancy for ER alpha and ER beta in the maintenance of the trabecular BMD was observed in the female mice at 60 days of age. Thus, ER alpha and ER beta may have separate effects (regulation of fat), opposing effects (longitudinal bone growth) or partial redundant effects (trabecular BMD at 60 days of age), depending on which parameter is studied.

Circumstantial evidence for a role of the secretory pattern of growth hormone in control of body growth

1982 ◽  
Vol 99 (1) ◽  
pp. 24-30 ◽  
Author(s):  
John-Olov Jansson ◽  
Kerstin Albertsson-Wikland ◽  
Staffan Edén ◽  
Karl-Göran Thorngren ◽  
Olle Isaksson
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Replacement Therapy ◽  
Bone Growth ◽  
Injection Period ◽  
Longitudinal Bone Growth ◽  
Long Period ◽  
Hypophysectomized Rats ◽  
Secretory Pattern

Abstract. The effect of frequency of growth hormone (GH) administration on longitudinal bone growth and body weight was studied in hypophysectomized rats which were given replacement therapy with corticosteroids, thyroxine and GH with start of therapy on the day of surgery. Longitudinal bone growth, as determined by the tetracycline method, was measured during the last 5 days of the 9 day long period with replacement therapy. The daily replacement dose of GH (bGH-17:NIH) was 200 μg and was given on 1, 2, 4 or 8 occasions. Longitudinal bone growth was enhanced in the groups of animals receiving the hormone on two or more occasions per day. The most pronounced response was seen with an administration frequency of four times per day. Changes in body weight during the injection period showed similar changes. The results of the present study show that the administration frequency of growth hormone is important for the growth rate in hypophysectomized rats which have been given replacement therapy. The findings suggest that the secretory pattern of GH is an important factor for optimum growth.

The role of the G protein-coupled receptor GPR30 in the effects of estrogen in ovariectomized mice

2009 ◽  
Vol 296 (3) ◽  
pp. E490-E496 ◽  
Author(s):  
S. H. Windahl ◽  
N. Andersson ◽  
A. S. Chagin ◽  
U. E. A. Mårtensson ◽  
H. Carlsten ◽  
...  
Keyword(s):  
Growth Plate ◽  
Fat Mass ◽  
Bone Growth ◽  
Distal Femur ◽  
Uterine Weight ◽  
Marrow Cellularity ◽  
G Protein Coupled ◽  
Estrogenic Responses

In vitro studies suggest that the membrane G protein-coupled receptor GPR30 is a functional estrogen receptor (ER). The aim of the present study was to determine the possible in vivo role of GPR30 as a functional ER primarily for the regulation of skeletal parameters, including bone mass and longitudinal bone growth, but also for some other well-known estrogen-regulated parameters, including uterine weight, thymus weight, and fat mass. Three-month-old ovariectomized (OVX) GPR30-deficient mice (GPR30−/−) and wild-type (WT) mice were treated with either vehicle or increasing doses of estradiol (E2; 0, 30, 70, 160, or 830 ng·mouse−1·day−1). Body composition [bone mineral density (BMD), fat mass, and lean mass] was analyzed by dual-energy-X ray absorptiometry, while the cortical and trabecular bone compartments were analyzed by peripheral quantitative computerized tomography. Quantitative histological analyses were performed in the distal femur growth plate. Bone marrow cellularity and distribution were analyzed using a fluorescence-activated cell sorter. The estrogenic responses on most of the investigated parameters, including increase in bone mass (total body BMD, spine BMD, trabecular BMD, and cortical bone thickness), increase in uterine weight, thymic atrophy, fat mass reduction, and increase in bone marrow cellularity, were similar for all of the investigated E2 doses in WT and GPR30−/− mice. On the other hand, E2 treatment reduced longitudinal bone growth, reflected by decreased femur length and distal femur growth plate height, in the WT mice but not in the GPR30−/− mice compared with vehicle-treated mice. These in vivo findings demonstrate that GPR30 is not required for normal estrogenic responses on several major well-known estrogen-regulated parameters. In contrast, GPR30 is required for a normal estrogenic response in the growth plate.

scholarly journals The Role of the Growth Plate in Longitudinal Bone Growth

1991 ◽  
Vol 70 (8) ◽  
pp. 1806-1814 ◽  
Author(s):  
M. PINES ◽  
S. HURWITZ
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Longitudinal Bone Growth

5 alpha-Dihydrotestosterone partially restores cancellous bone volume in osteopenic ovariectomized rats

1994 ◽  
Vol 267 (6) ◽  
pp. E853-E859 ◽  
Author(s):  
J. H. Tobias ◽  
A. Gallagher ◽  
T. J. Chambers
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Growth ◽  
Bone Volume ◽  
Ovariectomized Rats ◽  
Trabecular Thickness ◽  
Longitudinal Bone Growth ◽  
Periosteal Bone Formation

Although androgens are thought to be important for skeletal maintenance in females and males, little is known about the mechanisms involved. To investigate this question further, we examined the effects of administering 0.01, 0.1, or 1.0 mg/kg 5 alpha-dihydrotestosterone (DHT) for 60 days on the skeleton of ovariectomized rats. Treatment was delayed until 90 days after ovariectomy to enable bone loss to stabilize. We found that ovariectomy markedly reduced cancellous bone volume of the proximal tibial metaphysis due to a combination of loss and thinning of trabeculae. Cancellous bone volume was partially restored by all doses of DHT, with trabecular thickness, but not number, returning to that of sham-operated animals. DHT also stimulated longitudinal bone growth and endosteal and periosteal bone formation and suppressed histomorphometric indexes of cancellous bone resorption. This suggests that DHT influences skeletal metabolism in osteopenic ovariectomized rats both by stimulating bone formation and suppressing resorption, although it is unclear which, if any, of these actions predominate at cancellous sites.

scholarly journals DHEA Suppresses Longitudinal Bone Growth by Acting Directly at Growth Plate through Estrogen Receptors

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1423-1433 ◽  
Author(s):  
Hongzhi Sun ◽  
Weijin Zang ◽  
Bo Zhou ◽  
Lin Xu ◽  
Shufang Wu
Keyword(s):  
Estrogen Receptor ◽  
Growth Plate ◽  
Bone Growth ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Skeletal Maturation ◽  
Chondrocyte Apoptosis ◽  
Chondrocyte Proliferation ◽  
Longitudinal Bone Growth ◽  
Growth Plate Chondrocyte

Abstract Dehydroepiandrosterone (DHEA) is produced by the adrenal cortex and is the most abundant steroid in humans. Although in some physiological and pathological conditions the increased secretion of DHEA and its sulfated form is associated with accelerated growth rate and skeletal maturation, it is unclear whether DHEA can affect longitudinal bone growth and skeletal maturation by acting directly at the growth plate. In our study, DHEA suppressed metatarsal growth, growth plate chondrocyte proliferation, and hypertrophy/differentiation. In addition, DHEA increased the number of apoptotic chondrocytes in the growth plate. In cultured chondrocytes, DHEA reduced chondrocyte proliferation and induced apoptosis. The DHEA-induced inhibition of metatarsal growth and growth plate chondrocyte proliferation and hypertrophy/differentiation was nullified by culturing metatarsals with DHEA in the presence of ICI 182,780, an inhibitor of estrogen receptor, but not in the presence of Casodex, an inhibitor of androgen receptor. Lastly, nuclear factor-κB DNA binding activity was inhibited by the addition of DHEA in the medium of cultured chondrocyte. Our findings indicate that DHEA suppressed bone growth by acting directly at growth plate through estrogen receptor. Such growth inhibition is mediated by decreased chondrocyte proliferation and hypertrophy/differentiation and by increased chondrocyte apoptosis.

scholarly journals Astragalus Extract Mixture HT042 Improves Bone Growth, Mass, and Microarchitecture in Prepubertal Female Rats: A Microcomputed Tomographic Study

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Jungbin Song ◽  
Sung Hyun Lee ◽  
Donghun Lee ◽  
Hocheol Kim
Keyword(s):  
Bone Mass ◽  
Cortical Bone ◽  
Bone Growth ◽  
Volume Fraction ◽  
Control Diet ◽  
Female Rats ◽  
Volumetric Bone Mineral Density ◽  
Mineral Density ◽  
Longitudinal Bone Growth ◽  
Tibial Length

Astragalus extract mixture HT042 is a standardized multiherbal mixture comprising Astragalus membranaceus, Eleutherococcus senticosus, and Phlomis umbrosa, which has proven to promote children’s height growth. The aim of this study was to investigate the effects of HT042 on longitudinal bone growth, bone mass, and bone microstructure in growing rats using a high-resolution microcomputed tomography system. Four-week-old female rats were fed an HT042-containing diet for 2 weeks. Tibial length was measured at baseline and weekly in vivo. At the end of the study, volumetric bone mineral density (vBMD) and microarchitectural parameters were estimated in the trabecular and cortical bone of the tibia. Tibial length gain was significantly increased by HT042 compared to that reported with the control diet. In the proximal tibial metaphysis, HT042-treated rats had significantly higher trabecular vBMD, bone volume fraction, and trabecular number and lower trabecular separation, trabecular pattern factor, and structure model index values than control rats did. Total cross-sectional area and bone area of the cortical bone in the tibial diaphysis also increased. These findings suggest that HT042 increases longitudinal bone growth rate, improves trabecular bone mass, and enhances the microarchitecture of trabecular and cortical bone during growth.

Sign in / Sign up

Export Citation Format

Share Document