title: Proliferation in hyperplastic human and normal rat parathyroid glands: role of phosphate, calcitriol, and gender.
abstract: BACKGROUND
  Parathyroid gland hyperplasia develops in azotemic patients. A phosphate excess and calcitriol deficiency play critical roles in its development. Our goals were to determine whether differences in serum phosphate values at parathyroidectomy (PTX) in hemodialysis patients with refractory hyperparathyroidism: (1) correlated with parathyroid cell proliferation; and (2) affected the antiproliferative response to in vitro calcitriol. Studies were also performed to determine whether the phosphate concentration in the medium affected the antiproliferative response to calcitriol, and whether a high phosphate diet and calcitriol treatment affected parathyroid cell proliferation and parathyroid hormone (PTH) levels in normal rats.
  
  
  METHODS
  Forty-seven parathyroid glands from 19 hemodialysis patients were obtained at PTX. Flow cytometry was used to determine cell proliferation (percent cells in S phase) in excised parathyroid glands. Similarly, cell proliferation was determined in parathyroid tissue incubated for 24 hours in medium with or without 10(-7) mol/L calcitriol and with 1 or 4 mmol/L phosphate. In normal rats, the effect of 3 days of a high phosphate diet (1.2% P) and calcitriol treatment (100 pmol/kg) on PTH values and cell proliferation was evaluated.
  
  
  RESULTS
  In cells from freshly removed parathyroid glands obtained at PTX from hemodialysis patients, there were no significant correlations between the percent cells in S phase and age, gender, and serum phosphate, calcium, and PTH. While incubation of parathyroid tissue with 10(-7) mol/L calcitriol did reduce cell proliferation (P < 0.001), both the pre-PTX serum phosphate value (P= 0.003) and female gender (P=0.003) were associated with a decreased response to calcitriol. Incubation of parathyroid tissue in medium containing 4 mmol/L phosphate did not increase cell proliferation. In normal rats, a high phosphate diet for 3 days increased cell proliferation (P < 0.05) and PTH levels (P < 0.05), and calcitriol treatment was without effect.
  
  
  CONCLUSIONS
  Our findings suggest a high phosphate burden, as well as female gender, favor parathyroid cell proliferation and both may reduce the inhibition of parathyroid function by calcitriol.
authors: Unit of Investigation, Hospital Universitario Reina Sofia, Cordoba, Spain.
authors: Yolanda
authors: Y
authors: Almaden
authors: Arnold J
authors: AJ
authors: Felsenfeld
authors: Mariano
authors: M
authors: Rodriguez
authors: Sagrario
authors: S
authors: Cañadillas
authors: Fernando
authors: F
authors: Luque
authors: Alicia
authors: A
authors: Bas
authors: Juan
authors: J
authors: Bravo
authors: Vicente
authors: V
authors: Torregrosa
authors: Alfonso
authors: A
authors: Palma
authors: Blanca
authors: B
authors: Ramos
authors: Carmen
authors: C
authors: Sanchez
authors: Alejandro
authors: A
authors: Martin-Malo
authors: Antonio
authors: A
authors: Canalejo
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D004032:Diet; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006965:Hyperplasia; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D010280:Parathyroid Glands / Q000473:pathology*; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000008:administration & dosage* / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D006435:Renal Dialysis; D012727:Sex Characteristics
chemical_list: D003470:Culture Media; D010281:Parathyroid Hormone; D010710:Phosphates; D002117:Calcitriol