Chromogranin-A (CgA) and parathyroid hormone (PTH) are the two major secretory products of the parathyroid gland. While CgA is believed to be important for cell secretory activity, its precise function(s) remain to be fully elucidated. The effects of the active metabolite of vitamin D, 1,25-dihydroxyvitamin D$ sb3$ (1,25(OH)$ rm sb2D sb3)$ were investigated on parathyroid gland CgA mRNA in the rat. Parathyroid CgA mRNA levels increased in a dose-dependent manner in response to injections of 1,257(OH)$ rm sb2D sb3$ whereas PTH mRNA levels decreased. CgA mRNA levels were less sensitive to 1,25(OH)$ rm sb2D sb3$ than PTH mRNA levels. Having established in vivo regulation of CgA by 1,25(OH)$ rm sb2D sb3,$ the potential role of altered expression of CgA in the pathophysiology of secondary hyperparathyroidism (2$ sp circ$HPT) was explored using the uremic rat model. Five-sixth (5/6) nephrectomized rats maintained on a normal diet had normal levels of serum calcium and phosphate but reduced levels of 1,25(OH)$ rm sb2D sb3.$ In these uremic rat parathyroid glands, whereas PTH mRNA levels were four-fold higher, CgA mRNA levels were 50% lower that those in sham-operated rats. In uremic rats maintained on a high phosphorus diet, 5/6 nephrectomy resulted in decreased serum calcium and 1,25(OH)$ rm sb2D sb3$ levels. These animals had elevated parathyroid CgA and PTH mRNA levels. Thus, in vivo, increased serum 1,25(OH)$ rm sb2D sb3$ concentrations stimulate, and decreased serum levels inhibit parathyroid CgA mRNA expression. However, this latter effect depends upon the calcium status of the animal. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.24042 |
| Date | January 1996 |
| Creators | Soliman, Eric |
| Contributors | Hendy, Geoffrey (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001528954, proquestno: MM19851, Theses scanned by UMI/ProQuest. |
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