Post-natal ontogeny of stanniocalcin gene expression in rodent kidney and regulation by dietary calcium and phosphate

Background. Stanniocalcin (STC) is a polypeptide hormone first discovered i n fish and more recently in mammals. In mammals, STC is produced in many ti ssues and does not normally circulate in the blood. In kidney and gut, STC regulates phosphate fluxes across the transporting epithelia, whereas in br ain it protects neurons against cerebral ischemia and promotes neuronal cel l differentiation. The gene is highly expressed in ovary and dramatically u p-regulated during pregnancy and nursing. Gene expression also is high duri ng mammalian embryogenesis, particularly in kidney where the hormone signal s between epithelial and mesenchymal cells during nephrogenesis. Methods. This study examined the patterns of STC gene expression and protei n distribution in the mouse kidney over the course of post-natal developmen t. Further, because STC is a regulator of renal phosphate transport, we als o examined the effects of changing levels of dietary calcium and phosphate on renal levels of STC gene expression in adult rats. Results. STC mRNA levels in the neonate kidney were found to be tenfold hig her than adults. Isotopic in situ hybridization of neonate kidneys revealed that most, if not all, STC mRNA was confined to collecting duct (CD) cells , as is the case in adults. STC protein on the other hand was found in prox imal tubule, thick ascending limb and distal tubules in addition to CD cell s. This suggests that, as in adults, the more proximal nephron segments in neonates are targeted by CD-derived STC and sequester large amounts of horm one. The addition of 1% calcium gluconate to the drinking water significant ly reduced STC mRNA levels in inner medullary CD cells of both males and fe males, but not those in the cortex and outer medulla. Placing animals on lo w phosphate diets also reduced STC mRNA levels, but uniquely in outer medul lary and cortical CD cells, whereas a high phosphate diet increased transcr ipt levels in the same regions. Conclusions. These findings suggest that STC may be of unique importance to neonates. They also suggest that changes in dietary calcium and phosphate can alter renal levels of STC gene expression, but that these effects vary between the early and late segments of the collecting duct.