OVARIECTOMY DECREASES THE MESSENGER-RNA LEVELS OF TRANSFORMING GROWTH-FACTOR-BETA-1 AND INCREASES THE MESSENGER-RNA LEVELS OF OSTEOCALCIN IN RAT BONE IN-VIVO

Estrogen depletion causes postmenopausal osteoporosis. Here we report that steady state mRNA levels of transforming growth factor-α1 (TGF-α1) and osteocalcin in bone persistently decreased and increased, respectively, in vivo in estrogen-depleted rats after ovariectomy (OVX). 21 female Wistar rats (7-month-old) were randomized and underwent OVX or sham-operation, total RNA was extracted from tibiae and assessed by Northern blot analysis. OVX induced 70-80% decrease in TGF-α1 mRNA levels and 2- to 3-fold increase in mRNA levels of osteocalcin compared with controls three weeks after surgery. These changes persisted up to twelve weeks post-operation. OVX caused 15% reduction in femoral bone mineral density and 2-fold elevation in serum osteocalcin levels as early as two weeks post-operation. Moreover, estrogen depletion resulted in marked decrease and increase, respectively, in steady state mRNA levels of TGF-α1 and osteocalcin in vitro in osteoblastic rat osteosarcoma cells, ROS 17/2.8. Our results provide the first in vivo evidence that expression of TGF-α and osteocalcin in bone is reciprocally regulated at the transcriptional level in estrogen deficient OVX rats and suggests that TGF-α1 may play a role in estrogen-dependent maintenance of normal bone density. © 1993 Academic Press, Inc.