Demonstration of Estrogen Receptor-β Immunoreactivity in Human Growth Plate Cartilage

Lo, Nilsson; Boman, Anders; Sävendahl, Lars; Grigelioniené, Giedré; Ohlsson, Claes; Em, Ritzén; Wróblewski, J

doi:10.1210/jcem.84.1.5531

Cited by 52 publications

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“…Our results indicate that both receptor types are present in an identical distribution within the distinct zones of the growth plate. In accordance with the results of Nilsson et al [14]our data suggest that the zone of hypertrophic chondrocytes is the major site of action for estrogens within the growth plate.…”

Section: Discussionsupporting

confidence: 93%

“…Detection of ER in bone and cartilage has been problematic in earlier studies, partly due to the low expression of ER in these tissues when compared to classical estrogen target tissue like the urogenital tract [10, 11]. Studies on intact tissue in the human growth plate are sparse and limited to the investigation of one of the two receptor types [12, 13, 14]. Whereas ER-α was detected in all zones of the growth plate by in situ hybridization and immunohistochemistry by Kusec et al [13], ER-β was only reported to be present in hypertrophic chondrocytes in an immunohistochemical study by Nilsson et al [14].…”

Section: Introductionmentioning

confidence: 99%

“…Studies on intact tissue in the human growth plate are sparse and limited to the investigation of one of the two receptor types [12, 13, 14]. Whereas ER-α was detected in all zones of the growth plate by in situ hybridization and immunohistochemistry by Kusec et al [13], ER-β was only reported to be present in hypertrophic chondrocytes in an immunohistochemical study by Nilsson et al [14]. It was speculated that a distinct expression pattern of both ERs might play a role in the effect of estrogens on growth plate chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

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Estrogen Receptor-Alpha and Estrogen Receptor-Beta Are Present in the Human Growth Plate in Childhood and Adolescence, in Identical Distribution

Egerbacher

Helmreich

Rossmanith³

et al. 2002

Horm Res Paediatr

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Objective: To localize estrogen receptor-α (ER-α) and estrogen receptor-β (ER-β) within the growth plate and adjacent bony tissue of children in the prepubertal and pubertal age period. Methods: Tissue was taken during orthopedic surgery (epiphysiodesis) for correction of congenital or traumatic leg length difference in 2 prepubertal females and 2 adolescent males. Immunohistochemistry was performed on paraffin-embedded or cryostat sections by using commercially available rabbit polyclonal antibodies for ER-α and ER-β. Results: Both ER-α and ER-β were detected within the growth plate in all sections investigated. Immunostaining was restricted to hypertrophic chondrocytes. In the bony tissue adjacent to the growth plate, osteoblasts stained positive for both ER-α and ER-β, whereas osteocytes and osteoclasts were negative. Staining with ER-α was mainly nuclear but some cells also showed cytoplasmic signals, while ER-β staining was predominantly cytoplasmic, only few nuclei stained positive. There was no difference in the local distribution of both ERs between tissue from prepubertal and pubertal patients. Conclusion: Our findings indicate that the hypertrophic chondrocyte is the main target cell for estrogen action within the growth plate. The presence of ER in prepubertal children suggests that estrogens play a role in skeletal maturation under physiological conditions also in this age-group.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Estrogen Receptor-Alpha and Estrogen Receptor-Beta Are Present in the Human Growth Plate in Childhood and Adolescence, in Identical Distribution

Egerbacher

Helmreich

Rossmanith³

et al. 2002

Horm Res Paediatr

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“…These receptors are commonly referred to as ER␣ and ER␤, and their expression has been described previously in skeletal cells (14)(15)(16)(17)(18)(19)(20). In humans, evidence for the importance of ER␣ for mediating effects of estrogen in the skeleton comes from a case report describing a young male with estrogen resistance caused by a mutation in the human ER␣ gene (21).…”

mentioning

confidence: 99%

Estrogen receptor specificity in the regulation of skeletal growth and maturation in male mice

Vidal

Lindberg²,

Hollberg³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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350

274

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Androgens may regulate the male skeleton directly through a stimulation of androgen receptors or indirectly through aromatization of androgens into estrogen and, thereafter, through stimulation of estrogen receptors (ERs). The relative importance of ER subtypes in the regulation of the male skeleton was studied in ER␣-knockout (ERKO), ER␤-knockout (BERKO), and double ER␣͞␤-knockout (DERKO) mice. ERKO and DERKO, but not BERKO, demonstrated decreased longitudinal as well as radial skeletal growth associated with decreased serum levels of insulin-like growth factor I. Therefore, ER␣, but not ER␤, mediates important effects of estrogen in the skeleton of male mice during growth and maturation.

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“…All three sex steroid receptors are expressed both in growth-plate cartilage and in bone (6)(7)(8)(9)(10)(11). Functional studies using sex steroid receptor-inactivated animal models have demonstrated that ER␣ but not ER␤ is important for the regulation of appendicular longitudinal skeletal growth in male mice (12)(13)(14), and a recent report indicates that AR-inactivated male mice have unaffected bone length (15).…”

mentioning

confidence: 99%

Differential effects on bone of estrogen receptor α and androgen receptor activation in orchidectomized adult male mice

Movérare

Venken

Eriksson

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

128

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Androgens may regulate the male skeleton either directly by stimulation of the androgen receptor (AR) or indirectly by aromatization of androgens into estrogens and, thereafter, by stimulation of the estrogen receptors (ERs). To directly compare the effect of ER activation on bone in vivo with the effect of AR activation, 9-month-old orchidectomized wild-type and ER-inactivated mice were treated with the nonaromatizable androgen 5␣-dihydrotestosterone, 17␤-estradiol, or vehicle. Both ER␣ and AR but not ER␤ activation preserved the amount of trabecular bone. ER␣ activation resulted both in a preserved thickness and number of trabeculae. In contrast, AR activation exclusively preserved the number of trabeculae, whereas the thickness of the trabeculae was unaffected. Furthermore, the effects of 17␤-estradiol could not be mediated by the AR, and the effects of 5␣-dihydrotestosterone were increased rather than decreased in ER-inactivated mice. ER␣, but not AR or ER␤, activation resulted in preserved thickness, volumetric density, and mechanical strength of the cortical bone. ER␣ activation increased serum levels of insulin-like growth factor I, which were positively correlated with all the cortical and trabecular bone parameters that were specifically preserved by ER␣ activation but not by AR activation, suggesting that insulin-like growth factor I might mediate these effects of ER␣ activation. Thus, the in vivo bone-sparing effect of ER␣ activation is distinct from the bone-sparing effect of AR activation in adult male mice. Because these two pathways are clearly distinct from each other, one may speculate that a combined treatment of selective ER modulators and selective AR modulators might be beneficial in the treatment of osteoporosis. S ex steroids are important not only for the maintenance of the female skeleton, but also for the male skeleton. The relative contribution of androgens versus estrogens in the regulation of the male skeleton is unclear. Testosterone replacement therapy increases bone mineral density (BMD) in hypogonadal men (1), but several clinical studies indicate that BMD is correlated more to serum levels of estradiol than to serum levels of testosterone in males (2-4). A previous clinical study, which directly compared estrogen versus testosterone effects on bone, showed that estrogens play the dominant role in the regulation of bone resorption markers, whereas both estrogens and testosterone contribute to the maintenance of markers for bone formation (5).The effects of testosterone can be exerted either directly by means of the androgen receptor (AR) or indirectly by aromatization to estrogens and further by estrogen receptor (ER)␣ and͞or ER␤. All three sex steroid receptors are expressed both in growth-plate cartilage and in bone (6-11). Functional studies using sex steroid receptor-inactivated animal models have demonstrated that ER␣ but not ER␤ is important for the regulation of appendicular longitudinal skeletal growth in male mice (12-14), and a recent report indicates that AR-inactivate...

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Demonstration of Estrogen Receptor-β Immunoreactivity in Human Growth Plate Cartilage

Cited by 52 publications

References 0 publications

Estrogen Receptor-Alpha and Estrogen Receptor-Beta Are Present in the Human Growth Plate in Childhood and Adolescence, in Identical Distribution

Estrogen Receptor-Alpha and Estrogen Receptor-Beta Are Present in the Human Growth Plate in Childhood and Adolescence, in Identical Distribution

Estrogen receptor specificity in the regulation of skeletal growth and maturation in male mice

Differential effects on bone of estrogen receptor α and androgen receptor activation in orchidectomized adult male mice

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