Influence of parathyroid mass on the regulation of PTH secretion E. Lewin, K. Olgaard  Kidney International  Volume 70, Pages S16-S21 (July 2006) DOI: 10.1038/sj.ki.5001597 Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 1 Expression of autocrine/paracrine factors might modulate parathyroid function. (a–b) Enhanced expression of PTHrP has been demonstrated in glands from patients with severe sec. HPT due to uremia. PTH/PTHrP receptor was demonstrated in the parathyroids. This figure shows the effect of N-terminal PTHrP on the secretory response of PTH to an acute induction of hypocalcemia in the rat. The rate of reduction of plasma-Ca2+ by an ethyleneglycol-bis(β-aminoethyl ether) N,N,N′,N′-tetraacetic acid (EGTA) infusion was similar in all groups of rats. A bolus of PTHrP 1–40, PTHrP 1–86, or vehicle was injected at time 0. PTHrP significantly enhanced by 300% (P<0.001) the low-Ca2+-stimulated PTH secretion in vivo. N=6 in each group, mean±s.e.m. Modified from Lewin et al.58 Kidney International 2006 70, S16-S21DOI: (10.1038/sj.ki.5001597) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 2 Even considerable parathyroid hyperplasia can be controlled in the normal organism. When 20 isogenic parathyroid glands were implanted into one PTX rat a short-lasting hypercalcemia was induced, soon followed, however, by normalization of Ca2+ and PTH levels. This figure shows plasma Ca2+ and plasma PTH levels in rats with 20 isogenic parathyroid glands implanted. Parathyroidectomy of their own parathyroid glands was performed on day 0, before the implantation of the 20 glands. The line (—) depicts plasma Ca2+ levels, while the bars depict PTH levels. N=6, mean±s.e.m. *P<0.05 versus the level at day 0, before PTX. Modified from Lewin et al.27 Kidney International 2006 70, S16-S21DOI: (10.1038/sj.ki.5001597) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 3 Severe parathyroid hyperplasia can be controlled when the functional demand for increased PTH levels is abolished by normalization of the kidney function. This figure shows kidney function and basal PTH levels before introduction of uremia by 5/6 nephrectomy (-20 weeks), during uremia (-20 to 0 weeks), and after reversal of uremia by an isogenic kidney transplantation (TX). The lines (—) depict kidney function expressed as plasma urea and the bars depict PTH levels. The uremic rats were kept on a high P diet. N=12, mean±s.e.m. Modified from Lewin et al.27 Kidney International 2006 70, S16-S21DOI: (10.1038/sj.ki.5001597) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 4 Suppressibility of PTH secretion by Ca2+ is not influenced by the parathyroid mass, itself. Parathyroid function was investigated by the Ca2+/PTH relationship during acute inductions of hypocalcemia and hypercalcemia in uremic rats kept on high P diet (Uremia-P), kidney transplanted, 3 weeks after transplantation (TX), and in normal control rats (controls). The PTH secretory response to hypocalcemia was significantly higher in uremic rats (P<0.001) than in kidney transplanted and normal control rats. The PTH secretion was suppressed to same extend in kidney transplanted rats and normal control rats, while uremic hyperphosphatemic rats had a significantly higher (P<0.05) PTH secretion at high Ca2+. N=6, mean±s.e.m. Modified from Lewin et al.27 Kidney International 2006 70, S16-S21DOI: (10.1038/sj.ki.5001597) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 5 Upregulation of the parathyroid CaR gene expression after reversal of uremia by kidney transplantation (TX) does not occur immediately. The expression of CaR was still diminished 1 week after TX, at a time when circulating PTH levels already were normalized. The figure shows the CaR gene expression in the parathyroid glands of normal control rats, uremic rats on a high P diet (CRF hP), and kidney transplanted (TX), 1 and 4 weeks after kidney transplantation. N=5–8, mean±s.e.m. *P<0.001 versus control rats. Kidney International 2006 70, S16-S21DOI: (10.1038/sj.ki.5001597) Copyright © 2006 International Society of Nephrology Terms and Conditions