Parathyroid Hormone Bindingin Vivoto Renal, Hepatic, and Skeletal Tissues of the Rat Using a Radioautographic Approach*

Abstract

We have examined in vivo binding of bovine (b) PTH-(1-84) and the analog [Nle8,18, Tyr34]bPTH-(1-34) amide to hepatic, skeletal, and renal rat tissues. Bioactive 125I-labeled bPTH-(1-84) or the 125I-labeled bPTH-(1-34) analog was injected alone into experimental animals or with either unlabeled PTH or unlabeled unrelated hormone into control animals. Corresponding tissues from experimental and control animals were then processed for light and electron microscope radioautography and analyzed quantitatively and qualitatively. Binding of both PTH forms occurred on hepatocytes and sinusoidal cells in liver, and hepatocyte binding was clearly specific and competitive. Intact PTH-(1-84), but not the amino-terminal fragment, bound to Kupffer cells, indicating a sequence-specific interaction. In bone, specific competitive PTH binding was seen over osteoblasts, but not osteoclasts. Skeletal PTH binding was also seen over connective tissue mononuclear cells, and sinusoidal endothelial cells. In kidney, specific competitive PTH binding was seen over glomerular podocytes, and over the antiluminal surface of cells of the proximal tubule, the thick ascending limb of Henle's loop, and the distal tubule. Noncompetitive binding was seen on the luminal surface of proximal convoluted tubule cells. We have, therefore, distinguished specific competitive binding sites, probably related to hormone action, from noncompetitive binding sites, presumably associated with hormone metabolism, on discrete cell types or cell regions within several tissues. Our approach provides morphological correlates to the biochemical interaction of PTH with its target tissues and should enhance our understanding of the relationship of target cell structure and function.

Vitamin D3 differentially regulates parathyroid hormone/parathyroid hormone-related peptide receptor expression in bone and cartilage

“…The distribution of PTHR coding sequences detected in mouse tibiae by in situ hybridization was essentially identical to that of P2-specific sequences, i.e., in chondrocytes extending from the proliferative zone to the upper region of the hypertrophic zone of the growth plate, and in both preosteoblasts and osteoblasts below the growth plate (Fig 5). This is consistent with our previous reports of in vivo binding of PTH and PTHrP to bone and cartilage cells (15,(45)(46)(47). D3 treatment markedly decreased the expression of the PTHR coding region in both preosteoblasts and osteoblasts.…”

Expression of parathyroid hormone-related protein in the rat glomerulus and tubule during recovery from renal ischemia.

“…This was substantiated by confocal microscopy. Receptors for PTH are known to be present on both mesangial and epithelial cells (37,38) ( 1-3).…”

Induction of osteoclast formation by parathyroid hormone depends on an action on stromal cells

“…Following an injection of PTH, there is a rapid increase in the activity of pre-existing osteoclasts, followed by an increase in osteoclast numbers (Bingham et al 1969, Baron & Vignery 1981. It is believed that PTH increases the resorptive activity of pre-existing osteoclasts through a primary hormonal interaction with cells of the osteoblastic lineage, which possess PTH receptors and responsiveness (Chambers 1980, Rodan & Martin 1981, while osteoclasts have been found in most (Rouleau et al 1986(Rouleau et al , 1988(Rouleau et al , 1990 but not all (Rao et al 1983, Teti et al 1991, Agarwala & Gay 1992 studies to lack PTH receptors, and do not show a direct functional response to the hormone (Chambers et al 1985). Much less is known, however, of the mechanism by which PTH induces osteoclast formation.…”