IMMUNOLOGICAL EVIDENCES FOR POSTTRANSLATIONAL CONTROL OF THE PARATHYROID FUNCTION BY IONIZED CALCIUM IN DOGS

To outline the role of post-translational events in the control of the parathyroid function in vivo, we have studied the parathyroid functio n of normal dogs receiving i.v. infusions of CaCl2 and Na2EDTA with in tact (I), carboxylterminal (C) and midcarboxylterminal (M) iPTH assays and evaluated the influence of ionized calcium on circulating molecul ar forms of iPTH via alterations in C/I, M/I and M/C iPTH ratios. Furt hermore, the use of the mathematical model fitting the sigmoidal relat ionship between ionized calcium and iPTH ratios was improved through t he generation of more iPTH ratio points in the ascending part of the s igmoid function. Quantitatively, the response to hypocalcemia was high est with M (98.7 +/- 36.8 pmol/l; P < 0.0167 vs. L and P < 0.0001 vs. I) and higher with L (83.1 +/- 26.1 pmol/l; P < 0.0001 vs. I) than wit h I (12.1 +/- 3.2 pmol/l). Similar results were observed for the non-s uppressible fraction of iPTH measured by the three iPTH assays in hype rcalcemia. The slope of the sigmoid function was more acute for I than for C or M, while all three secretion set-points were similar at 1.30 mmol/l. Qualitatively, all iPTH ratios increased from hypo- to hyperc alcemia, results being more pronounced for the M/I and C/I iPTH ratios (7.66 +/- 2.57 to 73.9 +/- 41.4 and 6.76 +/- 1.93 to 49.8 +/- 27.5) t han for the M/C iPTH ratio (1.24 +/- 0.48 to 1.82 +/- 1.16). The slope s of the three ratios were similar as were the set-points, but in this last case, values were higher (1.40 mmol/l) than for secretion set-po ints. These results indicate that dog parathyroid function is similar to that of man. The lower set-points for secretion and higher ones for regulating M/I and C/I iPTH ratios favor an optimal amount of I in fa ce of decreasing ionized calcium and permit to control the non-suppres sible fraction of iPTH secretion via M and C fragments production in f ace of increasing ionized calcium. These events are important to under stand the implication and signification of post-translationnal events in the parathyroid glands and in peripheral blood in the phenomenon of PTH immunoheterogeneity. They further outline that the tools used her e will be useful to study similar phenomenons in individuals in face o f diseased parathyroid glands.