ESTROGEN ENHANCES THE STIMULATION OF BONE-COLLAGEN SYNTHESIS BY LOADING AND EXOGENOUS PROSTACYCLIN, BUT NOT PROSTAGLANDIN E(2), IN ORGAN-CULTURES OF RAT ULNAE

The shafts of ulnae from 110 g male rats were cultured, and after a pe riod of 5 h preincubation one of each pair of bones was either loaded cyclically (500 g, 1 Hz, 8 minutes) to produce physiologic strains (-1 300 mu epsilon) or treated with exogenous prostacyclin (PGI(2)) or pro staglandin E(2) (10(-6) M, 8 minutes) in the presence or absence of 17 beta-estradiol (10(-8) M). PGI(2), PGE(2), and loading stimulated alm ost immediate increases in glucose 6-phosphate dehydrogenase (G6PD) ac tivity in osteocytes and osteoblasts. This increase was uniform throug hout the section with exogenous PGs in the medium but was related to l ocal strain magnitude in loading. Elevated G6PD levels in response to loading and PGI(2) persisted for 18 h, by which time, ALP activity in surface osteoblasts was elevated and [H-3]proline incorporation into c ollagen increased. PGE, produced similar immediate and sustained incre ases in G6PD activity and [H-3]proline incorporation after 18 h but no change in ALP activity. Bones cultured for 18 h with 17 beta-estradio l increased their [H-3]proline incorporation, as did those loaded, and treated with PGI(2) and PGE(2). Loading and PGI(2) but not PGE(2) pro duced similar proportional increases in [H-3]proline incorporation abo ve the increased baseline of estradiol alone. These results suggest th at estrogen and loading together produce a greater osteogenic response than either separately. If so, estrogen withdrawal would result in a rapid fall in bone mass to establish a new equilibrium appropriate to the reduced effectiveness of the loading-related stimulus. Such a fall in bone mass is a characteristic feature of estrogen withdrawal at th e menopause.