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.