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...

Stanniocalcin (STC) is a glycoprotein hormone first identified in bony fishes where it counteracts hypercalcemia by inhibiting gill calcium uptake and stimulating renal inorganic phosphate (P i ) reabsorption. Human STC (hSTC) has recently been cloned and sequenced and is highly homologous to the fish hormone at the amino acid level. The objective of this study was to examine the possible effects of hSTC on electrolyte homeostasis and renal function in the rat. Recombinant hSTC was expressed in bacteria and purified by metal-ion affinity chromatography and reverse-phase high performance liquid chromatography. Anesthetized animals were given bolus infusions of 1, 5, or 10 nmol hSTC per kilogram of body weight. Control animals received solvent alone. The most effective dosage was 5 nmol/kg, which caused significant reductions in both absolute and fractional phosphate excretion in comparison with control rats. The hSTC had no effect on the renal excretion of other ions, the glomerular filtration rate, renal blood flow, blood pressure, or plasma electrolytes (Na

(1) EtOH-mediated gastric mucosal injury appears to be a neutrophil-mediated process. (2) Neutropenia results in an increase in mucosal NO synthesis. (3) MT treatment augments the degree of mucosal integrity. The increase in integrity is associated with a reduction in mucosal neutrophil infiltration as well as maintenance of NO synthase activity. ANS appears to influence mucosal integrity primarily by a reduction in circulating neutrophils.

Epidermal growth factor (EGF) originating from salivary glands has been shown to affect the development and integrity of rodent gastrointestinal mucosa. Because newborn rats receive EGF from maternal milk, we have examined the effect of sialoadenectomy as a method of depleting EGF in milk on the resistance of neonatal rat mucosa to luminal H+. Rat dams were sialoadenectomized (SALX) or sham operated 5 days after parturition. Experiments were performed on newborns 10-22 days old. Mucosal permeability responses to intraluminal HCl (300 mM) were examined in terms of luminal appearances of Na+, K+, and protein and H+ loss. EGF levels in maternal milk were determined by immunoassay. In rat pups from control litters, luminal HCl resulted in an age-associated increase in cation and protein flux across the gastric mucosa. Luminal cation and protein fluxes observed in 10- to 18-day-old rat pups from SALX dams were not significantly different from similarly aged rats from control dams. However, in 19- to 22-day-old rats from SALX dams, the permeability responses to luminal HCl were exacerbated compared with similarly aged neonates from control dams. These responses were reduced by treatment with EGF. EGF levels in milk from sham-operated and SALX dams were not significantly different in the 10- to 16-day lactational period. However, in SALX dams EGF was significantly reduced at 19 and 22 days. Chromatographic elution pattern of milk EGF was dissimilar to the pattern exhibited by submandibular gland EGF.(ABSTRACT TRUNCATED AT 250 WORDS)