Prospect of a stanniocalcin endocrine/paracrine system in mammals

Stanniocalcin (STC) is a calcium- and phosphate-regulating hormone produced in bony fish by the corpuscles of Stannius, which are located close to the kidney. It is a major antihypercalcemic hormone in fish. As the corpuscles of Stannius are absent, and antihypercalcemic hormones are basically not necessary, in mammals, the discovery of a mammalian homolog, STC1, was surprising and intriguing. STC1 displays a relatively high amino acid sequence identity (approximately 50%) with fish STC. In contrast to fish STC, STC1 is expressed in many tissues, including kidney. More recently, a human gene encoding the second stanniocalcin-like protein, STC2, was identified. STC2 has a lower identity (approximately 35%) with STC1 and fish STC. Similar to STC1, STC2 is also expressed in a variety of tissues. Research into the functions of STCs in mammals is still at an early stage, and the ultimate physiological and pathological roles of STCs have not yet been established. A few studies indicate that STC1, similar to fish STC, stimulates phosphate absorption in the kidney and intestine, but the function of STC2 is still unknown. However, several interesting findings have been reported on their cellular localization, gene structure, and expression in different physiological and pathological conditions, which will be clues in elucidating the functions of STCs in mammals. STC1 expression is enhanced by hypertonicity in a kidney cell line or by ischemic injuries and neural differentiation in the brain. STC1 expression in the ovary is also enhanced during pregnancy and lactation. Calcitriol upregulates STC1 and downregulates STC2 expression in the kidney. Interestingly, STC1 and STC2 are expressed in many tumor cell lines, and the expression of STC2 is enhanced by estradiol in breast cancer cells. STC2 is also expressed in pancreatic islets. These results suggest that the biological repertoires of STCs in mammals will be considerably larger than in fish and may not be limited to mineral metabolism. This brief review describes recent progress in mammalian STC research.