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Molecular Endocrinology, Vol 9, 805-813, Copyright © 1995 by Endocrine Society

ARTICLES

Estrogen enhances alpha v beta 3 integrin expression by avian osteoclast precursors via stabilization of beta 3 integrin mRNA

CF Li, FP Ross, X Cao and SL Teitelbaum
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Although bone resorption is accelerated with menopause, the means by which diminished circulating 17 beta-estradiol (E2) promotes osteoclastic activity are unknown. We hypothesized that since the integrin alpha v beta 3 is essential to the resorptive process, reduced E2 levels may increase the integrin's expression by osteoclast precursors. Thus, avian osteoclast precursors (known to contain E2 receptors) were exposed +/- E2, surface iodinated, and lysed. The lysate was immunoprecipitated with an antibody recognizing the intact alpha v beta 3 heterodimer. We find E2 alone fails to impact on alpha v beta 3 expression. Most importantly, however, picomolar (i.e. post- menopausal), but not nanomolar (i.e. premenopausal) concentrations of E2, when added in conjunction with 1,25-dihydroxyvitamin D3 [1,25- (OH)2D3], enhance alpha v beta 3 expression on the plasma membrane of avian osteoclast precursors relative to 1,25(OH)2D3 alone. Induction of alpha v beta 3 by picomolar levels of E2 is dose-dependent, maximizing at 10(-11)-10(-12) M, wherein the sex steroid enhances 1,25-(OH)2-D3- stimulated integrin expression approximately 2.5-fold. Northern analysis reveals that beta 3 mRNA levels parallel those of alpha v beta 3. E2 (10(-12) M) increases expression of beta 3 mRNA induced by a range of 1,25-(OH)2D3 concentrations extending from 10(-10) m-10(-8) M. The E2 + 1,25-(OH)2D3 additive effect on beta 3 mRNA appears as early as 1 day of treatment and progresses for at least 3 days. Consistent with evidence that the beta 3 subunit regulates heterodimer expression, the sex steroid does not impact alpha v mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)


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