The stanniocalcin family of proteins

Abstract

Stannniocalcin (STC) is a polypeptide hormone that was originally identified in bony fishes as a systemic regulator of mineral metabolism, and is best known for its regulatory effects on calcium/phosphate transport by the gills, gut and kidneys. The mammalian homolog to fish STC was discovered in 1995 and has resulted in progressively growing interest ever since as to its possible role in humans. Moreover, new discoveries in the mammalian STC field are resulting in significant reappraisals as to its role in fishes. Perhaps the most significant of these has been the discovery of a second gene encoding stanniocalcin-related protein, or STC-2, first in mammals and subsequently in fish. This review covers the comparative endocrinology of the STCs in fishes and mammals from the perspectives of structure, function and regulation. It then delves into some of the newer aspects of STC-1/STC-2 biology that have been uncovered using both classical and transgenic approaches. Of these, one of the most intriguing discoveries relates to the receptor-mediated sequestration of STC by target cell organelles. The functions of other newly discovered mammalian and fish STC variants are also discussed, as is the recent discovery of STC-related homologs in invertebrates. Based on our current state of knowledge, it is apparent that STC has an ancient lineage and that the STC family of proteins is proving to have significant roles in metabolism, reproduction and development.

Parathyroid hormone-related protein-stanniocalcin antagonism in regulation of bicarbonate secretion and calcium precipitation in a marine fish intestine

“…5) and indicates a mechanism for its hypocalcemic action demonstrated in other in vivo and in vitro models (3,28,34,36). In our in vitro system, the intestinal absorptive calcium pathway was unaffected by application of STC 1 (Fig.…”

“…A model for calcium regulation that incorporates a single endocrine factor, stanniocalcin (STC), has been proposed in fish. It is justified on the basis of the nearly endless calcium pool available in seawater, the absence of parathyroid glands in fish, and the presence of fish-specific corpuscles of Stannius, which produce STC, a hypocalcemic or antihypercalcemic factor (3,28,34,36). However, this model is thrown into doubt by 1) the recent identification of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) in fish tissues and 2) their demonstrated role in calcium regulation as hypercalcemic factors (2, 4, 9 -11, 19, 25).…”

Multiple signaling pathways involved in stimulation of osteoblast differentiation by N-methyl-D-aspartate receptors activation in vitro

“…In epithelial cells and fibroblasts, MMP12 and MMP13 could be up-regulated in a PI3K, PKCδ and ERK1/2-dependent manner [33] . The stanniocalcins, comprising Stc1 and Stc2, are secreted homodimeric glycoprotein hormones with little homology to other proteins [34] . Stc1 was originally identified as a hormone secreted by the corpuscles of the stannius inteleost fish [35] and in fish appears to function primarily in the prevention of hypercalcaemia mediated via the ability of Stc1 to reduce calcium uptake by gills and inhibit intestinal calcium transport in the gut [36][37][38] .…”

Identification ofNTN4, TRA1, andSTC2as Prognostic Markers in Breast Cancer in a Screen for Signal Sequence Encoding Proteins

“…Two related mammalian genes have been identified, STC1 and STC2, both of which are predicted to be secreted glycosylated proteins (reviewed in refs. 33,34). STC1 and STC2 are expressed in a variety of tissues including endocrine glands and hormone-responsive organs, and ectopic constitutive expression of either stanniocalcin in transgenic mice results in postnatal growth retardation and, in the case of STC2, neonatal morbidity.…”