The Journal of Bone and Joint Surgery, Vol 76, Issue 5 713-721, Copyright © 1994 by Journal of Bone and Joint Surgery, Inc
Direct modulation of osteoblastic activity with estrogen
RJ Majeska, JT Ryaby and TA Einhorn
Department of Orthopaedics, Mount Sinai School of Medicine, New York, N.Y. 10029-6574.
Estrogens play an important but poorly understood role in the maintenance
of skeletal mass. Whereas the mechanisms of estrogen action on bone may be
complex, the finding that osteoblasts express estrogen receptors suggests
that this class of hormones exerts direct effects on bone cells. To
understand how estrogens regulate osteoblastic function, the
physiologically active estrogen metabolite 17 beta-estradiol was tested to
determine its effects on the well characterized murine osteoblastic
cell-line MC3T3-E1. Experiments were designed to identify the effects of
estrogen on osteoblastic activities associated with both the formation and
the resorption of bone. Estrogen treatment coordinately increased DNA
content and alkaline phosphatase activity in MC3T3-E1 cells as much as
twofold. The stimulatory effect on alkaline phosphatase was stereospecific,
dose-dependent between 0.1 and ten nanomolar, and dependent on the time in
culture when the hormone was administered. The effect was also persistent,
since alkaline phosphatase activity remained elevated for several days
after withdrawal of the hormone. Estrogen increased the levels of messenger
RNA for alkaline phosphatase and type-I collagen as well, and these effects
also persisted after removal of the hormone. The levels of messenger RNA
for osteopontin, another bone-matrix protein, were only slightly affected
by estrogen. Finally, estrogen inhibited the activation of adenylate
cyclase by three osteotropic agents known to stimulate the resorption of
bone: parathyroid hormone, prostaglandin E2, and the beta-adrenergic
agonist isoproterenol. Thus, estrogen promoted the expression of traits
associated with the formation of bone while reducing cellular
responsiveness to hormones that may trigger the resorption of
bone.(ABSTRACT TRUNCATED AT 250 WORDS)
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