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Author(s): Matthew J. Mahon [1]; Mark Donowitz [2]; C. Chris Yun [2]; Gino V. Segre (corresponding author) [1] The parathyroid hormone 1 receptor (PTH1R) is a class II G-protein-coupled receptor [...]

The RaKCaR Ca2+/polyvalent cation-sensing receptor was cloned to determine changes in the concentrations of extracellular Ca2+/polyvalent cations in kidney cells. Glomeruli cells exhibited RakCaR messenger ribonucleic acid and parathyroid hormone/parathyroid hormone-related protein coexpression. The coexpression of the two receptors in the glumeruli regulate the reabsorption of divalent cations and inhibited the stimulatory effects of parathyroid hormone.

Cells cultured from osteosarcoma cells respond to vitamin D by reducing the synthesis of parathyroid hormone-parathyroid hormone related peptide (PTH-PTHrP) receptors. These cells showed the lowest amounts of mRNA for PTH-PTHrP receptors by 72 hours of exposure to 1,25-dihidroxyvitamin D3 and remained in this conditions even after 4 days of exposure to control medium. The vitamin was not implicated in the degradation of existing receptors.

Parathyroid hormone/parathyroid hormone-related peptide (PTH/PTHrP) receptor mRNA is expressed in convoluted and straight proximal tubules, glomerular podocytes, the cortical region of thick ascending limbs, and distal convoluted tubules. Northern blot analysis reveals a new 4.0 kb PTH/PTHrP receptor transcript in cultured human glomerular podocytes. The existence of PTH/PTHrP receptor mRNA in tubular segments is correlated with the established sites of PTH action.

A study on the effect of calcitriol on calcium-modulated parathyroid hormone (PTH) secretion in patients with secondary hyperparathyroidism shows that PTH release during hypocalcemia is altered by calcitriol. Calcitriol, however, does not affect the set point for PTH release. Calcitriol diminishes serum PTH levels, but helps regain the secretory reserve of hyperplastic parathyroid tissues during hypocalcemia.

The role of parathyroid hormone-related peptide (PTHrP) in the induction of parietal endoderm differentiation in the preimplantation mouse embryo was investigated. The messenger RNA for PTH/PTHrP receptors is induced during the differentiation of endodermal cells, concomitant with the appearance of these receptors that are already coupled with adenylate cyclase. PTHrP was detected from the late morula stage onwards, mainly in developing trophectoderm cells. PTHrP was also found in the first endoderm derivatives of the inner cell mass at the blastocyst stage. The results suggest that PTHrP may be an inducer of differentiation in preimplantation development.

The role of parathyroid hormone in the metabolism of vitamin D in osteoporosis is examined. Three groups of subjects were included in the study: postmenopausal women with osteoporosis, women in the same age range (49 to 79 years) with no osteoporosis, and young women with no osteoporosis. The results of the study help to establish the relative effects of aging and osteoporosis on vitamin D metabolism. Parathyroid hormone stimulates an enzyme which converts vitamin D to its active form, 1,25-dihydroxyvitamin D(sub.3). This regulatory reaction is impaired in the aged and in cases of osteoporosis, resulting in reduced formation of the active vitamin D metabolite. A reduction in vitamin D metabolite is one of the primary causes of bone mineral loss in osteoporosis. When oral phosphate was administered to all three groups, all subjects experienced a rise in serum phosphate and a decrease in serum calcium, but changes in levels of parathyroid hormone and 1,25(OH)(sub.2)D varied. Both control groups experienced no change in levels of 1,25(OH)(sub.2)D while experiencing a rise in parathyroid hormone levels; the older women experienced a significantly higher rise. The osteoporotic subjects had a much smaller increase in parathyroid hormone and a drop in 1,25(OH)(sub.2)D level. Patients with osteoporosis do not appear to be able to produce an adequate parathyroid hormone response after stimulation to maintain the vitamin D homeostasis required to conserve bone mineral content. More work is needed to allow a more complete understanding of the role of abnormal vitamin D metabolism in osteoporosis.