EVIDENCE OF A CORRELATION OF ESTROGEN-RECEPTOR LEVEL AND AVIAN OSTEOCLAST ESTROGEN RESPONSIVENESS

Isolated osteoclasts from 5-week-old chickens respond to estradiol tre atment in vitro with decreased resorption activity, increased nuclear proto-oncogene expression, and decreased lysosomal enzyme secretion, T his study examines osteoclasts from embryonic chickens and egg-laying hens for evidence of estrogen responsiveness, Although osteoclasts fro m both of these sources express estrogen receptor mRNA and protein, es tradiol treatment had no effect on resorption activity, In contrast to the lack of effect on resorption, estradiol treatment for 30 minutes resulted in steady-state mRNA levels of c-fos and c-jun increasing in osteoclasts from embryonic chickens and decreasing in osteoclasts from egg-laying hens, These data suggest that a nuclear proto-oncogene res ponse may not be involved in estradiol-mediated decreased osteoclast r esorption activity, To examine the influence of circulating estrogen o n osteoclast estrogen responsiveness, 5-week-old chickens were injecte d with estrogen for 4 days prior to sacrifice, Estradiol treatment of osteoclasts from these chickens did not decrease resorption activity i n vitro, Transfection of an estrogen receptor expression vector into o steoclasts from the estradiol-injected chickens and egg-laying hens re stored estrogen responsiveness, Osteoclasts from 5-week-old chickens a nd estradiol treated 5-week-old chickens transfected with the estrogen receptor expression vector contained significantly higher levels of e strogen receptor protein and responded to estradiol treatment by decre asing secretion of cathepsins B and L and tartrate-resistant acid phos phatase. In contrast, osteoclasts from embryonic chickens, egg-laying hens, and estradiol-treated 5-week-old chickens either untransfected o r transfected with an empty expression vector did not respond similarl y, These data suggest that modulation of osteoclast estrogen responsiv eness may be controlled by changes in the osteoclast estrogen receptor levels.