Molecular and morphological approach of uremia-induced hyperplastic parathyroid gland following direct maxacalcitol injection.
The mechanisms explaining the clinical effects of direct maxacalcitol (OCT) injection into the hyperplastic parathyroid gland (PTG) in uremic patients with advanced secondary hyperparathyroidism (SHPT) were investigated by molecular and morphological examination. PTG of uremia-induced SHPT model rats were treated by a direct injection of OCT (DI-OCT) or vehicle (DI-vehicle). The changes in serum intact parathyroid hormone (intact-PTH) level, vitamin D and Ca-sensing receptor (VDR and CaSR, respectively) expression levels in PTG, and the calcium (Ca)-PTH response curve were examined; the induction of apoptosis in parathyroid cells (PTC) was also analyzed by the TUNEL method, DNA electrophoresis, and electron microscopic examination. Serum intact-PTH level following DI-OCT significantly decreased. Upregulation of both VDR and CaSR, a clear shift to the left downward in the Ca-PTH curve, and many apoptotic PTCs were observed in the DI-OCT-treated PTGs. However, these findings were not observed in the DI-vehicle-treated PTGs. Moreover, these effects were confirmed by the DI-OCT into one PTG and DI-vehicle alone into another PTG in the same rat. DI-OCT may introduce simultaneous VDR and CaSR upregulation and the regression of hyperplastic PTG, and these effects may provide a strategy for strongly suppressing PTH level in uremia-induced advanced SHPT.
Shiizaki
Kazuhiro
K
Division of Nephrology, Department of Internal Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, Japan. shiizaki@jichi.ac.jp
Hatamura
Ikuji
I
Nakazawa
Eiko
E
Ogura
Manabu
M
Masuda
Takahiro
T
Akizawa
Tadao
T
Kusano
Eiji
E
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001842:Bone and Bones / Q000002:abnormalities / Q000187:drug effects / Q000473:pathology; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000150:complications; D006965:Hyperplasia; D007150:Immunohistochemistry; D007267:Injections; D023421:Models, Animal; D009929:Organ Size / Q000187:drug effects; D010280:Parathyroid Glands / Q000187:drug effects* / Q000473:pathology*; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D014511:Uremia / Q000150:complications / Q000473:pathology*
D000970:Antineoplastic Agents; D010281:Parathyroid Hormone; D002117:Calcitriol; C051883:maxacalcitol; D002118:Calcium