Comparative Analysis of Mammalian Stanniocalcin Genes**This work was supported by grants from London Health Sciences Research, Inc. (to G.E.D.), the London Regional Cancer Center (to G.E.D.), and the Medical Research Council of Canada (to G.F.W.).

Abstract

The recent discovery of mammalian stanniocalcin (STC) prompted an investigation of its gene structure and expression pattern to study its function and regulation. We show that both the human and mouse genes are composed of four exons spanning about 13 kb, with 85% nucleotide sequence identity in coding regions. Remarkably high sequence conservation between species also exists in the approximately 3-kb 3'-untranslated region. Comparative analysis of the 5'-untranslated region and flanking DNA from the rat and human STC genes showed long stretches of CAG trinucleotide repeats and an additional (CA)25 dinucleotide repeat unique to the rat promoter. An analysis of STC expression in the mouse showed that ovary contained the highest level of messenger RNA, with lower, but detectable, levels in most tissues. In situ hybridization revealed strong, specific hybridization over the thecal-interstitial cells of the ovarian stroma, whereas immunohistochemical analysis indicated that STC was present not only in the stroma, but also in the corpora lutea and oocyte of the developing follicle. Consequently, STC may act as a signaling molecule between the thecal-interstitial cell compartment and the corpus luteum and oocyte, thereby regulating the activity of these structures in some way. These findings suggest that in addition to its role in mineral metabolism, STC has acquired an important function in reproduction during its evolution to mammals.

Characterization of Mammalian Stanniocalcin Receptors

“…Notably, several other tissues showed lower levels of specific binding, including lung, brain, skeletal muscle, and spleen. Because all of these latter tissues express the STC gene and/or contain high levels of STC immunoreactivity (35)(36)(37), it was not surprising that they exhibited varying degrees of specific binding. The precise localization of receptors in these tissues will form the basis of future studies.…”

Stanniocalcin-1 as a Novel Marker to Detect Minimal Residual Disease of Human Leukemia

“…The sequence similarity of STC-1 to its fish counterparts suggests that human homologue, STC-1, regulates calcium and phosphate homeostasis in the kidney and intestine (Chang et al 1996a, b;Wagner et al 1997;Koide et al 1998;Madsen et al 1998;Varghese et al 1998). Human STC-1 mRNA is, however, expressed in multiple tissues, suggesting that human STC-1 might have additional functions, for example, neural cell differentiation (Zhang et al 1998), bone formation (Yoshiko et al 1998;Stasko et al 2001).…”

Targeting of Big Stanniocalcin and Its Receptor to Lipid Storage Droplets of Ovarian Steroidogenic Cells

“…By far the highest levels of STC gene expression are observed in the ovary (1), where the transcript is confined to theca and interstitial cells (TIC). Interestingly, STC protein is found not only in TICs but also in oocytes and cells of the corpus luteum (1), suggesting that the STC is produced by TICs for targeting to oocytes and luteal cells.…”

“…Interestingly, STC protein is found not only in TICs but also in oocytes and cells of the corpus luteum (1), suggesting that the STC is produced by TICs for targeting to oocytes and luteal cells. The fact that the protein is readily detectable in cells that do not make the hormone further suggests that, as in the case of STC 50 signaling in liver and kidney (2), ovarian STC is also sequestered by its target cells.…”

“…The ability of luteal cells to sequester STC to an extent readily detectable by immunocytochemistry (1,4) implies the presence of STC receptors and/or binding proteins in these cells. In this regard, we recently used an STC⅐alkaline phosphatase (AP) fusion protein (STC⅐AP) to characterize receptors and delineate the mitochondrial targeting of STC 50 in liver and kidney (2).…”