Effect of ACTH on PTH-stimulated bone resorption in vitro
- 27 Downloads
In vitro demonstration of PTH effects requires hormone concentrations greater than the “physiological” concentrations reported by radio-immunoassay or cytochemical assays. This discrepancy could be the result of binding or destruction of PTH at nonbiologically active sites.
In the present study, ACTH was found to have no effect by itself on bone resorption, but addition of ACTH to bone cultures together with low concentrations of PTH resulted in a specific enhancement of PTH-stimulated bone resorption. This effect was not observed when bone resorption was stimulated by PGE2 and 1,25(OH)2D3, and it was blocked by human serum.
The effect of ACTH is similar to the enhancement in PTH-stimulated bone resorption by poly-l-lysine .
We suggest that the amplification of PTH stimulation was the result of displacement of PTH from nonbiologically active sites, making more PTH available for binding to its biologically active receptor. An alternative explanation for our results was that ACTH prevented degradation of PTH by bone-derived proteolytic enzymes. Thus the sensitivity of bioassays for PTH could be improved by adding ACTH.
Key wordsBone resorption PTH ACTH Basic peptides
Unable to display preview. Download preview PDF.
- 1.Stern, P.H., Raisz, L.G.: Organ culture of bone. In D.J. Simmons, A.S. Kunin (eds.): Skeletal Research-an Experimental Approach. Academic Press, New York, 1978Google Scholar
- 4.Habener, J.F., Potts, J.T., Jr.: Chemistry biosynthesis, secretion, and metabolism of parathyroid hormone. In G.D.A. Aurbach, R.O. Greep, E.B. Astwood, S.R. Geiger (eds.): Handbook of Physiology, vol. VII, pp. 313–342. American Physiological Society, Washington, D.C., 1976Google Scholar
- 5.Chambers, D.J., Dunham, J., Zanell, J.M., Panous, J.A., Bitensky, L., Chayen, J.: A sensitive bioassay of parathyroid hormone in plasma, Clin. Endocrinol.9:375–379, 1978Google Scholar
- 6.Fenton, S., Somers, S., Heath, D.A.: Preliminary studies with the sensitive cytochemical assay for parathyroid hormone, Clin. Endocrinol9:381–384, 1978Google Scholar
- 7.Raisz, L.G., Bergmann, P.J., Dominguez, J.H., Price, M.A.: Enhancement of parathyroid hormone stimulated bone resorption by poly-L-lysine, Endocrinology (in press.)Google Scholar
- 10.Goltzman, D., Peytremann, A., Callahan, E., Tregear, G.W., Potts, J.T.: Analysis of the requirements for parathyroid hormone action in renal membranes with the use of inhibiting analogues, J. Biol. Chem.250:3199–3203, 1975Google Scholar
- 12.Rosenblatt, M., Mahaffey, J.E., Goldring, S.R., Dayer, J.M., Krane, S.M., Potts, J.T., Jr.: Parathyroid hormone inhibitors: biological properties in human fibroblast monolayer culture system, The Endocrine Society, 60th Annual Meeting, 142, 1978Google Scholar
- 13.Ramachandran, J., Chung, D., Li, C.H.: Adrenocorticotropins. XXXV. Aspects of structure-activity relationships of the ACTH molecule. Synthesis of a heptadecapeptide amide, an octadecapeptide amide and a nonadecapeptide amide possessing high biological activites, J. Am. Chem. Soc.87:2696–2708, 1965CrossRefPubMedGoogle Scholar
- 14.Freitag, J., Martin, K., Conrades, M., Slatopolsky, E.: Metabolism of bovine parathyroid hormone 1–84 (bPTH) by fetal rat calvaria, Clin. Res.26:414, 1978Google Scholar