Regulation of parathyroid hypertensive factor secretion by vitamin D3 analogs in parathyroid cells derived from spontaneously hypertensive rats

✍ Scribed by S.K. Sutherland; I. Nemere; C.G. Benishin

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 220 KB
• Volume: 96
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20528

✦ Synopsis

Abstract

Parathyroid hypertensive factor (PHF) is a novel substance secreted by the parathyroid gland (PTG), which is elevated in 30–40% of all hypertensive patients; specifically, the low‐renin subset. However, very little is known about the regulation of PHF secretion. Since the classical parathyroid regulator, 1,25‐dihydroxyvitamin D~3~ (1,25‐(OH)~2~D~3~), may be elevated concurrent with or preceding the development of low‐renin hypertension and elevated plasma PHF, we hypothesized that 1,25‐(OH)~2~D~3~ would stimulate PHF release. To test this hypothesis, PTG organ and cell cultures, derived from spontaneously hypertensive rats (SHR) and the normotensive genetic control Wistar Kyoto (WKY) rats, were exposed to various vitamin D~3~ metabolites and PHF release measured by ELISA. 1,25‐(OH)~2~D~3~ rapidly stimulated PHF release with enhanced sensitivity in SHR versus WKY cultures indicated by a leftward shift in the dose‐response curve, whereas 24,25‐dihydroxyvitamin D~3~ (24,25‐(OH)~2~D~3~) had the converse effect. Vitamin D~3~ analog “BT,” an agonist for the classical nuclear vitamin D receptor (1,25VDR~nuc~), was without effect suggesting a 1,25VDR~nuc~‐independent mechanism and potential involvement of the plasma membrane‐bound vitamin D receptor (1,25 D~3~‐MARRS). Interestingly, protein expression of the 1,25 D~3~‐MARRS was increased in SHR versus WKY parathyroid cells. In conclusion, these results support the idea that 1,25‐(OH)~2~D~3~ may contribute to elevated plasma PHF in the SHR. © 2005 Wiley‐Liss, Inc.