Effect of age on renal responsiveness to parathyroid hormone and calcitonin in rats

Abstract

The purpose of these studies was to determine whether the responsiveness of the kidney to parathyroid hormone (PTH) and calcitonin changed with age. Experiments were performed in young (3 months old), adult (12-14 months old) and old (22-24 months old) male Fischer 344 rats fed normal diets and thyroparathyroidectomized. Parathyroid hormone was administered i.p. at 24, 12 and 2 h before death and calcitonin was given i.p. at 12 and 2 h before death. Parathyroid hormone significantly increased the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) by renal slices from young but not adult or old animals. A similar age-related decline in the capacity of PTH to raise serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels was also seen. Parathyroid hormone significantly decreased tubular reabsorption of phosphorus, increased concentrations of urinary cyclic AMP (cAMP) and increased serum concentrations of calcium in all age groups. In contrast, calcitonin significantly increased 1,25-(OH)2D3 production by renal slices from both young and adult animals. Calcitonin decreased serum concentrations of calcium in young but not in adult rats. These results suggest that there are maturational changes in the PTH- and cAMP-dependent pathways in the kidney but not in the calcitonin- and cAMP-independent pathways. The changes in the PTH- and cAMP-dependent pathways affect the stimulation of 1,25-(OH)2D production but not the inhibition of phosphate transport.

Parathyroid hormone stimulation of the renal 25-hydroxyvitamin D-1α-hydroxylase—Effect of age and free radicals

“…In rats, with maturation and aging, the capacity of PTH to stimulate renal 1,25(OH) 2 D production also declines. Specifically, the capacity of the kidney to increase plasma 1,25(OH) 2 D in response to PTH given in vivo declines with age [5,6].…”

Drug and Hormone Effects on Vitamin D Metabolism

“…In clinical studies, Paget's disease patients treated with etidronate had higher 1,25(OH) 2 D 3 levels without significant changes in serum PTH, ionized calcium, or phosphate [85,500]. Lawson-Matthew et al [501] found increased 1,25(OH) 2 D 3 concentrations following shortterm oral etidronate treatment but decreased 1,25(OH) 2 D 3 levels after high-dose intravenous etidronate.…”

“…The inhibition of intestinal 24-hydroxylase activity and expression may spare 1,25(OH) 2 D 3 from deactivation and thereby result in enhanced l,25(OH) 2 D 3 -mediated activity [84]. The majority of in vitro data have supported the positive effect of calcitonin on 1,25(OH) 2 D 3 levels [85,86]. Similar to in vivo data, 1a-hydroxylase was stimulated by calcitonin in vitamin-D-deficient rat kidneys, post-TPTX [86].…”

Sodium‐dependent phosphate transport in primary cultures of renal tubule cells from young and adult rats

“…The extent of these age-related alterations are similar in adult (10-12 months) and old (18-24 months) rats of the Fischer 344 strain. In addition, the production of CAMP and 1,25(OH),D3 in renal slices are decreased in response to PTH in aging animals (Armbrecht et al, 1986(Armbrecht et al, , 1987.Kiebzak and Sacktor (1986) examined the phosphate transport in intact and parathyroidectomized (PTX) rats fed a low phosphate diet. They found that the agerelated decrease in adaptation to a low phosphate regime persisted in PTX animals.…”