PARATHYROID-HORMONE INCREASES CIRCULATING LEVELS OF FIBRONECTIN IN-VIVO - MODULATING EFFECT OF OVARIECTOMY

To explore the effect of PTH on circulating levels of fibronectin (FN) , adult female Sprague-Dawley rats were implanted with Alzet minipumps prepared to deliver 7 pmol/h . kg BW of either human PTH (1-34) or hu man PTH (1-84). Both forms of the hormone led to significant and progr essive increases in circulating levels of FN over the 72-h study perio d (P < 0.001). However, at every time point, circulating levels of FN with human PTH (hPTH) (1-84) infusion were significantly higher than w ith hPTH (1-34), such that at the end of the infusion, mean levels in the hPTH (1-34) group were 32.2 +/- 1.4 ng/ml, in the hPTH (1-84) grou p 93.8 +/- 5.4 ng/ml, and in the vehicle infused group 14.6 +/- 0.7 ng /ml. The greater agonist efficacy of hPTH (1-84) was not explained by differences in circulating levels of the hormones, and both forms of t he hormone were equipotent at stimulating cAMP production by ROS 17/2. 8 cells. However, hPTH (1-84) remained a more effective agonist than h PTH (1-34) at stimulating FN production in these cells (P < 0.001). Ne phrectomy did not blunt the ability of PTH to increase circulating FN in vivo, indicating that the kidney was not the source of the FN produ ced in response to PTH. Pretreament with the potent bisphosphonate APD to block bone resorption also did not blunt the in vivo response to P TH. Parathyroidectomy did not blunt the response. Cultured fetal rat b ones showed a significant 2.4-fold increase in FN production when trea ted with PTH. Consistent with our earlier in vitro studies (Endocrinol ogy, 135: 1639-1644, 1994), estrogen deficiency, induced by ovariectom y, significantly diminished the ability of PTH to increase circulating FN levels in vivo (P < 0.001). We conclude that PTH increases circula ting levels of FN in vivo and may be a physiologic regulator for the p lasma form of this glycoprotein. The effects of PTH on circulating FN may reflect the anabolic properties of the hormone in bone and the blu nted response following estrogen withdrawal could be a manifestation o f the diminished bone formation vis-a-vis resorption seen in the estro gen deficient state.