Evidence for stanniocalcin binding activity in mammalian blood and glomerular filtrate

The 50 kD form of the hormone stanniocalcin-1 (STC50) is widely distributed in organs such as kidney, lung, and liver. Kidney collecting duct cells produce STC50 for local targeting to proximal tubule cells to increase phosphate reabsorption. As such the current dogma is that in most organs STC50 is a purely local mediator that is not released into the circulation. However, liver hepatocytes contain high levels of both STC50 and its receptor but little evidence of STC production, suggesting that the hormone may in fact be delivered to hepatocytes systemically. Moreover, previous data suggest that red blood cells may in fact bind STC. In this report, we have sought to identify STC binding activity in mammalian blood.

Human, pig, and dog red blood cells were analyzed in STC receptor binding assays. Mouse red blood cells and adult mouse kidney were also analyzed histologically for the presence of STC ligand and receptor.

Saturable, high affinity STC receptors were identified on red blood cells from all species. More intriguingly, STC binding activity was also identified in glomerular filtrate, indicative of a soluble, filterable STC binding protein. This binding protein was subsequently observed being reabsorbed in proximal straight tubules.

These findings suggest that our inability to detect STC in mammalian serum is due to its being attached to soluble and tethered forms of a high-affinity binding protein. This could be a means of delivering STC to distant targets as well as a mechanism for removing unwanted hormone from the circulation.