Androgen action on renal calcium and phosphate handling: Effects of bisphosphonate treatment and low calcium diet

Rougin Khalil, Ioannis Simitsidellis, Na Ri Kim, Ferran Jardi, Dieter Schollaert, Ludo Deboel, Philippa Saunders, Geert Carmeliet, Frank Claessens, Dirk Vanderschueren, Brigitte Decallonne

Research output: Contribution to journalArticlepeer-review

Abstract

Renal calcium and phosphate handling is an important contributor to mineral homeostasis and bone health and the androgen receptor (AR) is highly expressed in the kidney. We investigated the short term effects of androgen deprivation on renal calcium and phosphate reabsorption, independent of their effects on bone. Two weeks following orchidectomy (ORX) of adult mice, bone loss occurred along with hypercalciuria, which was similarly prevented by testosterone and dihydrotestosterone supplementation. Treatment with bisphosphonates prior to ORX also inhibited hypercalciuria, indicating that the calcium flux originated from the bone. Renal calcium and phosphate transporter expression was increased post-ORX, independent of bisphosphonates. Furthermore, an- drogen deprivation appeared to stimulate local synthesis of 1,25(OH)2D3. When bisphosphonate-treated mice were fed a low calcium diet, bone resorption was no longer blocked and secondary hyperparathyroidism de- veloped, which was more pronounced in ORX mice than sham-operated mice. In conclusion, this study shows that androgen deprivation increased renal calcium and phosphate transporter expression, independent of bone, and underlines the importance of adequate intestinal calcium supply in circumstances of androgen deprivation and bisphosphonate treatment.

Original languageEnglish
Pages (from-to)110891
JournalMolecular and Cellular Endocrinology
Volume514
Early online date10 Jun 2020
DOIs
Publication statusE-pub ahead of print - 10 Jun 2020

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