Endocrine Abstracts (2018) 57 005 | DOI: 10.1530/endoabs.57.005

The effect of androgens on renal calcium and phosphate handling, independent of bone and in circumstances of low dietary calcium

Khalil Rougin1, Kim Na Ri1, Jardi Ferran1, Claessens Frank2, Vanderschueren Dirk1 & Decallonne Brigitte1

1Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Aging, KU Leuven, Leuven, Belgium; 2Molecular Endocrinology Laboratory, Department of Molecular Medicine, KU Leuven, Leuven, Belgium.

Aims: We have previously shown that orchidectomy (ORX) in adult mice induces hypercalciuria and upregulation of renal Ca2+ and PO43− transporters, but also bone loss already after 2 weeks. Pretreatment with risedronate inhibited bone resorption and hypercalciuria but confirmed the upregulation of renal Ca2+ and PO43− transporters, suggesting bone-independent renal effects of androgens. We hypothesize that androgens regulate renal Ca2+ and PO43− homeostasis, independent of the dietary Ca2+ content as well.

Methods: We performed ORX on 18-week-old male mice (vs SHAM) and pretreated all animals with risedronate. Mice were fed either a normal Ca2+ diet (NCD, 1%) or a low Ca2+ diet (LCD, 0.02%), while PO43− was unchanged (0.6%). At 1 and 2 weeks post-ORX, 24 hr urine (metabolic cages) and serum was collected. After sacrifice (2 w post-ORX), kidneys were taken for qPCR of Ca2+ and PO43− transporters, trabecular bone was analyzed by microCT (L5 vertebra), and femoral bone was analyzed for Ca2+ content by ashing.

Results: Serum Ca2+ and PO43−, and urinary Ca2+ excretion were similar under both diets, but PO43− excretion was significantly increased in both the SHAM and ORX groups (239 and 268%, P< 0.0001) under LCD diet. Under LCD, increased serum levels of 1,25-dihydroxyvitamin D and PTH were observed. While risedronate efficiently blocked ORX-induced bone loss under the NCD, microCT analysis revealed that bone resorption was not fully blocked under the LCD, with a decrease in bone volume density of 14% compared to the NCD fed SHAM mice (P < 0.05). Also the femur Ca2+ content was significantly reduced in the LCD group (7.2 vs 8.8 mg in the NCD fed SHAM mice, P< 0.0001). Under the NCD, an increase of renal Ca2+ and PO43− transporter expression after ORX was confirmed. In the LCD group a small but significant additional increase of renal Ca2+ transporter expression was observed, with a 1.7-fold increase for TRPV5, a 2.1-fold increase for CaBP9K and a 1.5-fold increase for PMCA (vs respectively a 1.6-, 1.5- and 1.3-fold increase for the NCD). Expression of PO43− transporters (NaPi-2c, PiT1, PiT2) was similar in both diet groups.

Conclusions: Low dietary Ca2+ results in secondary hyperparathyroidism with LCD-induced bone loss despite treatment with bisphosphonates, and an additional increase in renal Ca2+ transporters. These findings underline the importance of adequate dietary Ca2+ intake along with anti-resorptive drugs in circumstances of bone loss post-androgen deprivation.

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