title: Parathyroid growth and regression in experimental uremia.
abstract: Early 1,25-dihydroxyvitamin D(3) (VD(3)) therapy during the course of renal failure prevents the downregulation of VD(3) receptor (VDR), calcium-sensing receptor (CaSR) or p21, and the parathyroid (PT) growth. We hypothesized that VD(3) could restore the decreased expressions of VDR and CaSR, and cause regression in enlarged PT glands. 5/6 nephrectomized rats fed high-phosphorus diet were killed at 1, 3, 5, or 7 days and at 2, 3, 4, 8, or 12 weeks. VD(3)-treated rats were given VD(3) intraperitoneally for 1, 2, 3, or 4 weeks, starting 8 weeks after 5/6 nephrectomy. PT glands were weighed and subjected to immunohistochemical analyses for VDR, CaSR, p21, Ki67, and Tdt-mediated dUTP nick end-labeling (TUNEL) assay. The area per cell was measured as the parameter of cell size. The expression of VDR and p21 began to decrease at day 1, and Ki67 increased at day 3, but decreased thereafter. There was a significant increase in PT gland weight to week 12 with the increase of cell size. VD(3) treatment significantly increased both VDR and CaSR expressions 2 weeks after the start of injection, and reduced the PT gland weight at week 3 with significant increase of TUNEL-positive cells and decrease of cell size. Our results suggest that PT growth in uremic rats involves both PT cell proliferation and hypertrophy, in association with the reduction of VDR, CaSR, and p21 expressions. In addition, VD(3) treatment could reverse PT hyperplasia and hypertrophy via restoration of these proteins.
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, and Kidney Care Unit, Kyushu University, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
authors.forename: M
authors.initials: M
authors.lastname: Tokumoto
authors.forename: D
authors.initials: D
authors.lastname: Matsuo
authors.forename: K
authors.initials: K
authors.lastname: Tsuruya
authors.forename: H
authors.initials: H
authors.lastname: Hirakata
authors.forename: M
authors.initials: M
authors.lastname: Iida
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006984:Hypertrophy / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis / Q000235:genetics / Q000502:physiology; D008297:Male; D009392:Nephrectomy; D009929:Organ Size; D010280:Parathyroid Glands / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000032:analysis / Q000235:genetics / Q000502:physiology; D044169:Receptors, Calcium-Sensing / Q000032:analysis / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014511:Uremia / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D002117:Calcitriol