Summary
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 [7].
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.
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References
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, 1978
Marcus, R., Arvesen, G., Orner, F.B.: Fluctuation of 3′,5′-cyclic adenosine monophosphate binding site occupancy as an index of hormone-dependent adenosine 3′,5′-monophosphate formation in bone cells, Endocrinology104:744–750, 1979
Nissenson, R.A., Arnaud, C.D.: Properties of the parathyroid hormone receptor-adenylate cyclase system in chicken renal plasma membranes, J. Biol. Chem.254:1469–1475, 1979
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., 1976
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, 1978
Fenton, S., Somers, S., Heath, D.A.: Preliminary studies with the sensitive cytochemical assay for parathyroid hormone, Clin. Endocrinol9:381–384, 1978
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.)
Raisz, L.G., Nieman, I.: Effect of phosphate, calcium, and magnesium on bone resorption and hormonal responses in tissue culture, Endocrinology85:446–452, 1969
Wolff, J., Cook, G.H.: Stimulation of hormone effects by polycations, Endocrinology101:1767–1775, 1977
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, 1975
Tregear, G.W., van Rietschoten, J., Greene, E., Keutmann, H.T., Niall, H.D., Reit, B., Parsons, J.A., Potts, J.T., Jr.: Bovine parathyroid hormone: minimum chain length of synthetic peptide required for biological activity, Endocrinology93:1349–1353, 1973
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, 1978
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, 1965
Freitag, J., Martin, K., Conrades, M., Slatopolsky, E.: Metabolism of bovine parathyroid hormone 1–84 (bPTH) by fetal rat calvaria, Clin. Res.26:414, 1978
Giordano, N.D., Sayers, T.G.: Isolated adrenal cells: assay of ACTH in rat serum, Proc. Soc. Exp. Biol. Med.136:623–626, 1971
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Dominguez, J.H., Raisz, L.G. Effect of ACTH on PTH-stimulated bone resorption in vitro. Calcif Tissue Int 30, 205–208 (1980). https://doi.org/10.1007/BF02408629
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DOI: https://doi.org/10.1007/BF02408629