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Parathyroid Hormone Increases Circulating Levels of Fibronectin in Vivo: Modulating Effect of Ovariectomy¹

Departments of Internal Medicine, Surgery, and Comparative Medicine, Yale School of Medicine,New Haven, Connecticut 06520

Address all correspondence and requests for reprints to: Ben hua Sun, M.D., Endocrine Section, Fitkin I, P. O. Box 208020, Yale School of Medicine, New Haven, Connecticut 06520-8020.

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 human PTH (1–84). Both forms of the hormone led to significant and progressive increases in circulating levels of FN over the 72-h study period (P < 0.001). However, at every time point, circulating levels of FN with human PTH (hPTH) (1–84) infusion were significantly higher than with 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) group 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 the hormone were equipotent at stimulating cAMP production by ROS 17/2.8 cells. However, hPTH (1–84) remained a more effective agonist than hPTH (1–34) at stimulating FN production in these cells (P < 0.001).

Nephrectomy did not blunt the ability of PTH to increase circulating FN in vivo, indicating that the kidney was not the source of the FN produced in response to PTH. Pretreament with the potent bisphosphonate APD to block bone resorption also did not blunt the in vivo response to PTH. Parathyroidectomy did not blunt the response. Cultured fetal rat bones showed a significant 2.4-fold increase in FN production when treated with PTH.

Consistent with our earlier in vitro studies , estrogen deficiency, induced by ovariectomy, significantly diminished the ability of PTH to increase circulating FN levels in vivo (P < 0.001).

We conclude that PTH increases circulating levels of FN in vivo and may be a physiologic regulator for the plasma form of this glycoprotein. The effects of PTH on circulating FN may reflect the anabolic properties of the hormone in bone and the blunted response following estrogen withdrawal could be a manifestation of the diminished bone formation vis-à-vis resorption seen in the estrogen deficient state.

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