ADAPTATION OF PARATHYROID FUNCTION TO INTRAVENOUS 1,25-DIHYDROXYVITAMIN D-3 OR PARTIAL PARATHYROIDECTOMY IN NORMAL DOGS

Parathyroid function was studied in 14 normal dogs 1 month before and after daily i.v. administration of 1,25-dihydroxyvitamin D-3 (1,25-(OH )(2)D-3) (eight dogs), or about 50% parathyroidectomy (six dogs), to t est the hypothesis that degradation of newly synthesized intact parath yroid hormone (I-PTH) is involved in parathyroid gland adjustment to a modified demand for I-PTH. Parathyroid function was studied through i .v. infusions of Na(2)EDTA and CaCl2 and measurement of ionized calciu m (Ca2+), I-PTH and carboxyl-terminal PTH (C-PTH) at various time poin ts. The C-PTH/I-PTH ratio was used as an index for change in the relat ive proportion of circulating C-PTH vs I-PTH, 1 month prior to and fol lowing each intervention. This ratio was further validated by looking at the HPLC profile of I-and C-PTH in hypo-and hypercalcemia under exp erimental conditions. Basal Ca2+ was unaltered 1 month after surgery, and was maintained constant in the 1,25-(OH)(2)D-3-treated group by gr adually decreasing 1,25-(OH)(2)D-3 doses over time from 0.25 to 0.13 m u g twice daily during the last week of the experimental protocol. In this same group, basal 1,25-(OH)(2)D-3 was increased by 65% (P<0.0001) and basal I-PTH was decreased by 40% (P<0.05), while basal C-PTH and the C-PTH/I-PTH ratio remained unchanged. Stimulated and non-suppressi ble I-and C-PTH followed the same pattern with, this time, an increase of stimulated and non-suppressible C-PTH/I-PTH ratio of 60% (P<0.05) and 85% (P<0.05) respectively. There was no change in basal I-PTH, C-P TH, or C-PTH/I-PTH ratio after surgery. However, stimulated I-and C-PT H were decreased by 45% (P<0.005) and 65% (P<0.005) respectively, with a 30% (P<0.005) decrease of stimulated C-PTH/I-PTH ratio. There was n o change in nonsuppressible I-PTH, while non-suppressible C-PTH decrea sed by 55% (P<0.005), with a 55% (P<0.05) decrease in non-suppressible C-PTH/I-PTH ratio. The HPLC profiles of I- and C-PTH obtained in hypo -and hypercalcemia disclosed a similar distribution of the immuno-reac tivity into peaks before and after i.v. administration of 1,25-(OH)(2) D-3 as well as partial parathyroidectomy. This indicated that C-PTH/I- PTH ratio changes were related to different circulating levels of I- a nd C-PTH rather than to a different composition of I- and C-PTH. These data indicate a shift in the circulating PTH profile toward more PTH carboxyl-terminal fragments after 1 month of i.v. 1,25-(OH)(2)D-3 but toward more intact PTH 1 month after about 50% parathyroidectomy, poss ibly reflecting adjustments in PTH degradation induced by a modified d emand for I-PTH. Although these changes are most likely modulated at t he parathyroid gland level, we cannot formally eliminate participation of the hormone's peripheral metabolism.