Human stanniocalcin: a possible hormonal regulator of mineral metabolism.

Abstract

We have isolated a human cDNA clone encoding the mammalian homolog of stanniocalcin (STC), a calcium-and phosphate-regulating hormone that was first described in fishes where it functions in preventing hypercalcemia. STC has a unique amino acid sequence and, until now, has remained one of the few polypeptide hormones never described in higher vertebrates. Human STC (hSTC) was found to be 247 amino acids long and to share 73% amino acid sequence similarity with fish STC. Polyclonal antibodies to recombinant hSTC localized to a distinct cell type in the nephron tubule, suggesting kidney as a possible site of synthesis. Recombinant hSTC inhibited the gill transport of calcium when administered to fish and stimulated renal phosphate reabsorption in the rat. The evidence suggests that mammalian STC, like its piscine counterpart, is a regulator of mineral homeostasis.Stanniocalcin (STC) is a calcium-regulating hormone in bony fishes that has never been described in higher vertebrates, including mammals (1). The hormone is synthesized by the corpuscles of stannius (CS), endocrine glands that are associated with the kidneys of all fishes with a bony skeleton (2). The primary function of STC in fishes is the prevention of hypercalcemia and a rise in serum calcium levels is the primary stimulus for secretion (3). Upon release into the circulation, STC lowers calcium transport by the gills thereby reducing its rate of influx from the environment into the extracellular compartment (1). A second equally important action of STC is stimulation of phosphate reabsorption by renal proximal tubules (4). The consequence of this renal effect is increased levels of plasma phosphate, the latter of which combines with excess calcium and promotes its disposal into bone and scales. Because the CS have never been identified in higher vertebrates, it has long been assumed that STC was unique to fishes. However, recent evidence of STC immunoreactivity in human kidney and serum argues for a more widespread existence of the hormone (5).By a process of random sequencing of human tissue cDNAs, we have isolated a lung-derived cDNA clone whose deduced protein sequence bears a strikingly high level of homology to salmon and eel STC (6, 7). § Data indicating that human (h)STC inhibits calcium uptake in fish and phosphate excretion in rats suggest that hSTC is a hormonal regulator of mineral metabolism. MATERIALS AND METHODScDNA Isolation and Analysis. cDNA isolation. The initial expressed sequence tag (EST) clones used in the study were discovered by scientists at The Institute for Genomic Research by using established EST methods (8, 9). These clones wereThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.part of a larger EST project (10). This clone was used for rescreening the same library and a full-length clone encoding hSTC was obtained.Southern blot analysis. Ten-microgram aliquo...

Regulation of microRNA expression by HMGA1 proteins

“…Stanniocalcin1, encoded by STC1 gene, is a glycoprotein hormone and it has a role in many physiological processes, including bone development, reproduction, wound healing, angiogenesis and modulation of inflammatory response (Ishibashi and Imai, 2002;Chang et al, 2003). The STC1 gene is expressed in a wide variety of tissues, including the kidney, prostate, thyroid, bone and ovary (Chang et al, 1995;Olsen et al, 1996;Varghese et al, 1998). Recently, STC1 overexpression has been found in hepatocellular, colorectal, breast and medullary thyroid carcinomas (Fujiwara et al, 2000;Okabe et al, 2001;Watanabe et al, 2002;McCudden et al, 2004).…”

Stanniocalcin-1 acts in a negative feedback loop in the prosurvival ERK1/2 signaling pathway during oxidative stress

“…In fish, it functions as a classic hormone that is secreted from endocrine glands, the Corpuscles of Stannius, in response to hypercalcemia and inhibits uptake of calcium through the gills and gut (Wagner et al, 1988;Sundell et al, 1992). In mammals, STC1 is also a secreted glycoprotein (Jellinek et al, 2000), but although recombinant human STC1 was found to be capable of inhibiting the uptake of calcium through the gills of goldfish (Olsen et al, 1996), and of regulating the flux of calcium and phosphate across rat intestine (Madsen et al, 1998) and kidney (Wagner et al, 1997), there is no evidence that it has a physiologic role in regulating serum calcium in mammals. Instead, mammalian STC1 is expressed in a variety of tissues (Chang et al, 1995(Chang et al, , 1996Olsen et al, 1996) and is thought to have an autocrine or paracrine role, but the possibility of an intracellular role also is suggested by evidence that STC1 localizes to mitochondria (McCudden et al, 2002;Westberg et al, 2007a).…”

Synergistic effect of p53 on TSA-induced stanniocalcin 1 expression in human nasopharyngeal carcinoma cells, CNE2

“…It is secreted from the endocrine gland, corpuscle of Stannius and acts on the target tissues to regulate whole-body Ca 2C and P i homeostasis (Wagner et al 1993, Lu et al 1994. The mammalian homologue of STC1 was identified almost 15 years ago; its function, however, is largely not known (Chang et al 1995, Olsen et al 1996. Different from piscine, mammalian STC1 is expressed in a wide variety of tissues, acting on its target cells via autocrine/paracrine pathways (Varghese et al 1998, De Niu et al 2000.…”