Evidence for a Direct in Vitro Action of Sex Steroids on Rabbit Cartilage Cells during Skeletal Growth: Influence of Age and Sex*

Corvol, Marie-Thérèse; Carrascosa, Antonio; Tsagris, Lydia; Blanchard, Odile; Rappaport, R

doi:10.1210/endo-120-4-1422

Cited by 120 publications

(38 citation statements)

References 31 publications

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“…The findings indicate that both ER subtypes are expressed in resting and proliferative chondrocytes from birth through sexual maturation in both rats and rabbits. This hypothesis is consistent with previous in vivo (Strickland & Sprinz 1973, Jansson et al 1983 and in vitro (Corvol et al 1987, Blanchard et al 1991) studies, which suggests that estrogen acts directly on growth plate chondrocytes. Our findings are also consistent with a study performed by Gunther et al (1999), who used an ER antagonist to block estrogen-induced acceleration of skeletal development in a mouse model.…”

Section: Discussionsupporting

confidence: 93%

Estrogen receptor-alpha and -beta are expressed throughout postnatal development in the rat and rabbit growth plate

Nilsson

Abad²,

Chrysis³

et al. 2002

Journal of Endocrinology

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Estrogen regulates skeletal growth and promotes epiphyseal fusion. To explore the mechanisms underlying these effects we investigated the expression of estrogen receptor-(ER ) and -(ER ) in rat and rabbit growth plates during postnatal development, using immunohistochemistry. Immunoreactivity for ER and ER was observed in resting zone and proliferative zone chondrocytes at all ages studied for both rat (7, 14, 28 and 70 days of age) and rabbit (1, 7, 28 and 120 days of age). In the rat distal humerus and the rabbit proximal tibia, expression of both receptors in the hypertrophic zone was minimal at early ages, increasing only at the last time point prior to epiphyseal fusion. Expression was rarely seen in the hypertrophic zone of the rat proximal tibia, a growth plate that does not fuse until late in life. Therefore, we conclude that ER and ER are both expressed in the mammalian growth plate. The temporal and anatomical pattern suggests that ER expression in the hypertrophic zone in particular may play a role in epiphyseal fusion.

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Section: Discussionsupporting

confidence: 93%

Estrogen receptor-alpha and -beta are expressed throughout postnatal development in the rat and rabbit growth plate

Nilsson

Abad²,

Chrysis³

et al. 2002

Journal of Endocrinology

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“…This may be in line with our study, since OVX decreased the cell diameter in the proliferating zone, despite an increase in its width, indicating that matrix synthesis is downregulated when estrogen is deficient. In contrast, it has been shown that E 2 stimulates 35 S uptake by chondrocytes, implying increased chondrocyte differentiation (Corvol et al 1987, Blanchard et al 1991). An explanation for a reduced width of the hypertrophic zone could be that estrogen causes the rate of apoptosis or vascular invasion to exceed the rate of cartilage matrix synthesis (Turner & Evans 2000).…”

Section: Discussionmentioning

confidence: 96%

Evidence for genomic and nongenomic actions of estrogen in growth plate regulation in female and male rats at the onset of sexual maturation

Eerden

Emons²,

Ahmed³

et al. 2002

Journal of Endocrinology

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Recently, both estrogen receptor (ER) and were detected in growth plate chondrocytes of rats before sexual maturation, implying a role for estrogen at this stage. In this study, therefore, we investigated the effects of ovariectomy (OVX) or estrogen supplementation on parameters of longitudinal growth in 26-day-old rats, which were sexually immature at the start of the experiment. OVX caused an increase in body weight gain, tibial length and growth plate width due to an increased proliferating zone. This increase correlated with an increase in cell number, with a decrease in cell diameter and with increased proliferating cell nuclear antigen (PCNA) immunostaining compared with sham. Interestingly, the increase in proliferation was not caused by an increase in insulin-like growth factor-I (IGF-I) mRNA expression in the growth plate as assessed by real-time PCR. In contrast to OVX, 17 -estradiol (E 2 ) supplementation (0·5 mg/21 days) of 26-day-old female rats caused a strong decrease in body weight gain, tibial length and growth plate width. The latter was explained by a reduction of the proliferating zone width, which correlated with a reduced number of PCNA-positive cells (not significant) and by a reduction of the hypertrophic zone width. In male rats supplemented with E 2 , similar effects were observed compared with the females. ER and immunostaining was found predominantly in late proliferating and early hypertrophic chondrocytes. OVX did not affect ER expression but E 2 supplementation strongly decreased immunostaining for both ER and in both sexes. Besides E 2 , desoxyestrone (DE), an activator of nongenomic estrogen-like signaling (ANGEL) and 2-methoxyestradiol (2-MeO-E 2 ), a tissue-selective naturally occurring metabolite of E 2 , were administered to female and male rats of the same age. Compared with E 2 , these compounds had less pronounced, though significant, effects on some parameters of longitudinal growth in both sexes, especially on growth plate characteristics. In conclusion, E 2 may exert effects on longitudinal growth before and at the onset of sexual maturation, despite very low endogenous serum levels at these stages. There may be a role for nongenomic signaling in body weight gain, tibial length and growth plate width but genomic signaling prevails.

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“…While the growth-promoting effect of testosterone has been shown in humans (Attie et al 1990, Keenan et al 1993, and supported by observations on its direct effect on rabbit epiphyseal articular chondrocytes (Corvol et al 1987) and rat tibial EGP width (Ren et al 1989), the precise mechanism(s) of testosterone action is elusive. We found no change in hepatic IGF-I mRNA levels in response to testosterone administration, either over 12 h post injection, or after 10 days of continuous exposure to testosterone.…”

Section: Discussionmentioning

confidence: 99%

Testosterone effect on growth and growth mediators of the GH-IGF-I axis in the liver and epiphyseal growth plate of juvenile rats

Zung

Phillip²,

Chalew³

et al. 1999

Journal of Molecular Endocrinology

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Several studies have suggested that testosterone may have a direct, GH-independent effect on growth. In order to assess possible mechanism(s) whereby testosterone exerts its growth-promoting effect, we evaluated its effect on growth mediators of the GH-IGF-I axis, in both the liver and the epiphyseal growth plate (EGP). Testosterone was administered to peripubertal rats and the responses of mRNA of GH receptor, IGF-I, IGF-I receptor and IGF-binding proteins-1 and -3 (IGFBP-1 and IGFBP-3) as well as circulating IGF-I were evaluated in two time-related models: over 12 h after a single injection (short-term study) and 10 days after continuous administration (long-term study). Rats in the short-term study were castrated and were killed 1, 4, 6 and 12 h post injection. Rats in the long-term study were divided into two groups: castrated vs castrated and hypophysectomized, in order to assess the effect of testosterone in the presence and absence of GH. mRNA levels were determined by RNase protection assay, and serum IGF-I by RIA.Testosterone enhanced weight gain in the rats treated for 10 days, a change that was similar in the presence or absence of GH. This effect was relatively small, however, by comparison with the total weight gained without testosterone. Testosterone had no effect on hepatic IGF-I mRNA abundance but induced a reduction in circulating IGF-I levels, in both the short-and long-term study. Testosterone had no effect on hepatic GH receptor and IGFBP-3 mRNA levels but resulted in a transient, short-term elevation in IGFBP-1 mRNA levels that was maximal 4 h post injection.In the EGP, neither testosterone administration nor hypophysectomy had any effect on IGF-I and IGF-I receptor mRNA levels. However, testosterone increased GH receptor mRNA abundance after 10 days of continuous administration in hypophysectomized rats only.These data suggest that the effect of testosterone on growth (as assessed by weight gain) is small and is not mediated by changes in hepatic gene expression of IGF-I, IGF-I receptor, IGFBP-1, IGFBP-3 or circulating IGF-I. At the EGP, the testosterone effect on linear growth is not mediated through changes in mRNA abundance of IGF-I and IGF-I receptor. The small but significant elevation of GH receptor mRNA levels in hypophysectomized rats may suggest a testosterone-mediated augmentation of a GH effect at the target organ.

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Evidence for a Direct in Vitro Action of Sex Steroids on Rabbit Cartilage Cells during Skeletal Growth: Influence of Age and Sex*

Cited by 120 publications

References 31 publications

Estrogen receptor-alpha and -beta are expressed throughout postnatal development in the rat and rabbit growth plate

Estrogen receptor-alpha and -beta are expressed throughout postnatal development in the rat and rabbit growth plate

Evidence for genomic and nongenomic actions of estrogen in growth plate regulation in female and male rats at the onset of sexual maturation

Testosterone effect on growth and growth mediators of the GH-IGF-I axis in the liver and epiphyseal growth plate of juvenile rats

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