Studies of the Porcine Intestinal Calcitriol Receptor in Pseudo-Vitamin D Deficiency Rickets Type I

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Abstract
Calcitriol (1,25-dihydroxyvitamin D3) concentrations in plasma of humans and pigs with pseudo-vitamin D deficiency rickets type I (PVDRI) have been reported to be significantly lower than in normal subjects and animals. Sometimes, however, calcitriol concentrations are relatively high in these subjects and animals (50-80 pmol/l) and nevertheless clincial symptoms of rickets develop. We have studied whether or not the development of rachitic lesions in piglets with PVDRI is due to altered binding properties of the intestinal calcitriol receptor in addition to the defective renal production of calcitriol. PVDRI piglets with clinical and biochemical symptoms of rickets (hypocalcaemia, increase activity of alkaline phosphatase) and with calcitriol concentrations in plasma of 83.7 .+-. 4.2 pmol/l (n = 7) were used. They were compared with unaffected piglets with normal calcitriol concentrations (178.0 .+-. 17.7 pmol/l, n = 9). The equilibrium dissociation constant (Kd) of the receptor in the PVDRI piglets (0.31 .+-. 0.05 nmol/l) and in control piglets (0.33 .+-. 0.05 nmol/l) and the maximum binding capacity (Bmax.) (674 .+-. 103 and 719 .+-. 122 fmol/mg of protein, respectively) were not different (n = 9). The association rate constant (kass) at 4.degree. C [0.15 .times. 107 and 0.24 .times. 107 (mol/l)-1 min-1] and the dissociation rate constent (kdiss) (0.40 .times. 10-3 and 0.48 .times. 10-3 min-1; half-life of dissociation = 24.1 and 28.9 h, respectively) were also not different between diseased and control piglets. No differences between PVDRI and control piglets were also found for the relative molecular mass (47 500 and 47 700, respectively) and the Stokes'' radius (3.04 and 3.05 nm, respectively) of the calcitriol receptor. It is concluded that the intestinal calcitriol receptor of this animal model functions normally and that changes in binding properties and concentration of the intestinal calcitriol receptor do not contribute to the development of rachitic lesions in PVDRI piglets.

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