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Departments of Oncology (R.V., G.E.D.), Biochemistry (R.V., G.E.D.), and Physiology (C.K.C.W., H.D., G.F.W.), University of Western Ontario, and the London Regional Cancer Center (R.V., G.E.D.), London, Ontario, Canada N6A 4L6
Address all correspondence and requests for reprints to: Gabriel E. DiMattia, Ph.D., London Regional Cancer Center, 790 Commissioners Road, London, Ontario, Canada N6A 4L6. E-mail: dimattia{at}julian.uwo.ca
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.
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M. Paciga, C. R. McCudden, C. Londos, G. E. DiMattia, and G. F. Wagner Targeting of Big Stanniocalcin and Its Receptor to Lipid Storage Droplets of Ovarian Steroidogenic Cells J. Biol. Chem., December 5, 2003; 278(49): 49549 - 49554. [Abstract] [Full Text] [PDF]
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H. Y. Yeung, D. K. O. Chan, N. K. Mak, G. F. Wagner, and C. K. C. Wong Identification of Signal Transduction Pathways that Modulate Dibutyryl Cyclic Adenosine Monophosphate Activation of Stanniocalcin Gene Expression in Neuroblastoma Cells Endocrinology, October 1, 2003; 144(10): 4446 - 4452. [Abstract] [Full Text] [PDF]
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R. Varghese, A. D. Gagliardi, P. E. Bialek, S.-P. Yee, G. F. Wagner, and G. E. Dimattia Overexpression of Human Stanniocalcin Affects Growth and Reproduction in Transgenic Mice Endocrinology, March 1, 2002; 143(3): 868 - 876. [Abstract] [Full Text] [PDF]
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