title: Endothelin receptor antagonist prevents parathyroid cell proliferation of low calcium diet-induced hyperparathyroidism in rats.
abstract: Secondary hyperparathyroidism, one of the most frequently encountered disorders of the calcium homeostasis, is characterized by an increase in parathyroid epithelial (PT) cell number, which is crucial from a functional viewpoint. However, it is still unknown what factors are involved in PT cell proliferation. Endothelin-1 (ET-1), a vasoconstrictive peptide, has been shown to act as a mitogen in a variety of cell types. Rat PT cells are reported to synthesize ET-1 and possess its receptors. To test the hypothesis that ET-1 plays a role in PT cell proliferation, we used rat test subjects fed a low calcium diet for 8 weeks (low Ca rats). The number of the proliferating PT cells, measured by proliferating cell nuclear antigen immunostaining, was significantly increased, with striking immunoreactivity of ET-1 in the low Ca rats. An endothelin receptor antagonist, bosentan (100 mg/kg.day), prevented any increase in the proliferation of PT cells in the low Ca rats (14.3 +/- 2.7/1000 PT cells with no bosentan; 2.1 +/- 1.3 with bosentan; P < 0.01). These results indicate that ET-1 is involved in PT cell proliferation in vivo and suggest that blocking of ET receptors may become one of the important therapeutic strategies for preventing secondary hyperparathyroidism.
authors.affiliation: Department of Internal Medicine 3, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kanesaka
authors.forename: H
authors.initials: H
authors.lastname: Tokunaga
authors.forename: K
authors.initials: K
authors.lastname: Iwashita
authors.forename: S
authors.initials: S
authors.lastname: Fujimura
authors.forename: S
authors.initials: S
authors.lastname: Naomi
authors.forename: K
authors.initials: K
authors.lastname: Tomita
mesh_terms: D000818:Animals; D000077300:Bosentan; D002118:Calcium / Q000172:deficiency*; D002136:Calcium, Dietary; D002455:Cell Division / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology; D006961:Hyperparathyroidism / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D010280:Parathyroid Glands / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D002136:Calcium, Dietary; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D013449:Sulfonamides; D000077300:Bosentan; D002118:Calcium