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

B. C.J. van der Eerden, J. Emons, S. Ahmed, H. W. van Essen, C. W.G.M. Lowik, J. M. Wit, M. Karperien*

*Corresponding author for this work

Research output: Contribution to journalReview articlePopular

31 Citations (Scopus)

Abstract

Recently, both estrogen receptor (ER) α, and β 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, 17β-estradiol (E2) 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 E2, similar effects were observed compared with the females. ERα and β immunostaining was found predominantly in late proliferating and early hypertrophic chondrocytes. OVX did not affect ER expression but E2 supplementation strongly decreased immunostaining for both ERα and β in both sexes. Besides E2, desoxyestrone (DE), an activator of nongenomic estrogen-like signaling (ANGEL) and 2-methoxyestradiol (2-MeO-E2), a tissue-selective naturally occurring metabolite of E2, were administered to female and male rats of the same age. Compared with E2, these compounds had less pronounced, though significant, effects on some parameters of longitudinal growth in both sexes, especially on growth plate characteristics. In conclusion, E2 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.

Original languageEnglish
Pages (from-to)277-288
Number of pages12
JournalJournal of Endocrinology
Volume175
Issue number2
DOIs
Publication statusPublished - 1 Nov 2002
Externally publishedYes

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