Testosterone increases urinary calcium excretion and inhibits expression of renal calcium transport proteins.
Although gender differences in the renal handling of calcium have been reported, the overall contribution of androgens to these differences remains uncertain. We determined here whether testosterone affects active renal calcium reabsorption by regulating calcium transport proteins. Male mice had higher urinary calcium excretion than female mice and their renal calcium transporters were expressed at a lower level. We also found that orchidectomized mice excreted less calcium in their urine than sham-operated control mice and that the hypocalciuria was normalized after testosterone replacement. Androgen deficiency increased the abundance of the renal mRNA and protein of both the luminal transient receptor potential vanilloid-subtype 5 (TRPV5) and intracellular calbindin-D(28K) transporters, which in turn were suppressed by testosterone treatment. There were no significant differences in serum estrogen, parathyroid hormone, or 1,25-dihydroxyvitamin D3 levels between control and orchidectomized mice with or without testosterone. Moreover, incubation of primary rabbit connecting tubule and cortical collecting duct cells with a nonaromatizable androgen, dihydrotestosterone, reduced transcellular calcium transport. Thus, our study shows that gender differences in renal calcium handling are, in part, mediated by the inhibitory actions of androgens on TRPV5-mediated active renal calcium transport.
Hsu
Yu-Juei
YJ
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Dimke
Henrik
H
Schoeber
Joost P H
JP
Hsu
Shih-Che
SC
Lin
Shih-Hua
SH
Chu
Pauling
P
Hoenderop
Joost G J
JG
Bindels
René J M
RJ
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D064026:Calbindins; D002118:Calcium / Q000652:urine*; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D013196:Dihydrotestosterone; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009919:Orchiectomy; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism; D011817:Rabbits; D011944:Receptors, Androgen / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012727:Sex Characteristics; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*
D000728:Androgens; D064026:Calbindins; D015220:Calcium Channels; C499849:NCX1 protein, mouse; D011944:Receptors, Androgen; D064030:S100 Calcium Binding Protein G; D019831:Sodium-Calcium Exchanger; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; D013196:Dihydrotestosterone; D013739:Testosterone; D053499:Plasma Membrane Calcium-Transporting ATPases; C506954:Atp2b1 protein, mouse; D002118:Calcium