Development of a human stanniocalcin radioimmunoassay: serum and tissue hormone levels and pharmacokinetics in the rat

Stanniocalcin (STC) is a polypeptide hormone that was first discovered in f ish and recently identified in humans and other mammals. In fish STC is pro duced by one gland, circulates freely in the blood and plays an integral ro le in mineral homeostasis. In mammals, STC is produced in a number of diffe rent tissues and serves a variety of different functions. In kidney, STC re gulates phosphate reabsorption by proximal tubule cells, whereas in ovary i t appears to be involved in steroid hormone synthesis. However there is no information on circulating levels of STC in mammals or the regulation of it s secretion. In this report we have developed a radioimmunoassay (RIA) for human STC. The RIA was validated for measuring tissue hormone levels. Howev er human and other mammalian sera were completely devoid of immunoreactive STC (irSTC). To explore the possibility that mammalian STC might have a sho rt half-life pharmacokinetic analysis was carried out ill rats. STC pharmac okinetics were best described by a two compartment model where the distribu tion phase (t1/2(alpha)) equaled 1 min and the elimination phase (t1/2(beta )) was 60 min. However the STC in the elimination phase no longer crossreac ted in the RIA indicating it had undergone substantial chemical modificatio n, which could explain our inability to detect irSTC in mammalian sera. Whe n we compared the pharmacokinetics of human and fish STC in mammalian and f ish models the human hormone was always eliminated faster, indicating that human STC has unique structural properties. There also appears to be a uniq ue clearance mechanism for STC in mammals. Hence there are major difference s in the delivery and biology of mammalian STC. Unlike fishes, mammalian ST C does not normally circulate in the blood and functions instead as a local mediator of cell function. Future studies will no doubt show that this has had important ramifications on function as well. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.