Hypercalcemia fails to suppress elevated serum parathyroid hormone concentrations during lactation in rats

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Abstract
We have previously reported that increased serum immunoreactive parathyroid hormone (iPTH) in the lactating (L) rat is generally accompanied by hypocalcemia when diets containing 0.4% calcium (Ca) or less are fed. However, instances were also observed in which elevated iPTH levels did not coincide with a hypocalcemia signal. To test the hypothesis that iPTH levels can remain elevated even in the presence of hypercalcemia in lactation, a diet containing 1.2% Ca and 0.4% phosphorus (P) was fed to lactating rats in three experiments (A, B, and C) to achieve serum ionized calcium (ICa) levels approximately 10% above levels for nonmated (NM) controls. The serum ICa of NM controls fed the 1.2% Ca diet was slightly, but significantly, elevated, and serum iPTH (determined by an N-terminal specific assay) was significantly suppressed compared with NM controls fed a 0.4% Ca diet. In experiment A, L rats fed a 1.2% Ca diet had 81% higher serum iPTH levels than NM controls fed the same diet in spite of a mean (+SEM) ICa level of 1.77 + 0.05 mM for L rats versus 1.46 + 0.01 mM for NM controls; NM controls fed a 0.4% Ca diet had serum ICa of 1.37 + 0.01 mM. This novel finding of significantly higher iPTH and ICa in L compared with NM rats fed a 1.2% Ca and 0.4% P diet was confirmed in experiment B with eight rats in each group of L or NM rats fed either the 1.2% or the 0.4% Ca diet. In experiment C, Ca IP (3 mg per 100 g body weight), which raised the serum ICa level of 20 day L rats fed 1.2% Ca diet to 2.20 + 0.18 mM at 40 minutes postinjection, did not suppress the elevated serum iPTH level (14.5 + 1.2 pg/ml for L versus 11.3 + 0.6 for NM). In NM rats fed the 0.4% Ca diet, however, Ca IP caused a rise in serum ICa to 1.86 + 0.04 mM and suppressed serum iPTH from 11.9 + 0.7 to 9.5 + 0.4 pg/ml (p < 0.02) at 40 minutes. In experiment D injected iPTH-(1–34) disappeared from the circulation of L rats at a rate not significantly different from that in NM rats. It is suggested that during lactation PTH secretagogues other than hypocalcemia can stimulate PTH secretion so that even supraphysiological serum Ca levels do not suppress PTH secretion to the same degree as in NM rats.
Funding Information
  • NIH (HD 12496)