COMPARATIVE-ANALYSIS OF MAMMALIAN STANNIOCALCIN GENES

The recent discovery of mammalian stanniocalcin (STC) prompted an inve stigation of its gene structure and expression pattern to study its fu nction and regulation. We show that both the human and mouse genes are composed of four exons spanning about 13 kb,with 85% nucleotide seque nce 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 flankin g DNA from the rat and human STC genes showed long stretches of CAG tr inucleotide repeats and an additional (CA)(25) dinucleotide repeat uni que to the rat promoter. An analysis of STC expression in the mouse sh owed that ovary contained the highest level of messenger RNA, with low er, but detectable, levels in most tissues. In situ hybridization reve aled 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 compartm ent and the corpus luteum and oocyte, thereby regulating the activity of these structures in some way. These findings suggest that in additi on to its role in mineral metabolism, STC has acquired an important fu nction in reproduction during its evolution to mammals.