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Secretory klotho interacts with parathyroid hormone (PTH) receptors
Author(s) -
Takenaka Tsuneo,
Inoue Tsutomu,
Miyazaki Takashi,
Suzuki Hiromichi
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb708
Subject(s) - klotho , parathyroid hormone , parathyroid hormone receptor , endocrinology , medicine , receptor , chemistry , kidney , hormone receptor , calcium , cancer , breast cancer
Background We have previously demonstrated that chronic administration of secretory klotho into rats with adriamycin nephropathy retards renal injury and reduced vitamin D without changes in PTH levels (J Am Soc Nephrol. 2011; 22: 776A). Membrane‐type klotho acts as a receptor for FGF23. Klotho is expressed on cell membrane of parathyroid glands. Although FGF23 can act on parathyroid glands, direct effects of secretory klotho on PTH receptors have not been examined. Klotho is known to binds to receptors to WNT and TGF‐beta. Methods The interactions of secretory klotho and PTH receptors were examined under in vitro and in vivo conditions. Sepharose‐beads coated with protein G was mixed with antibody to PTH receptors in test tube. Then, PTH receptor was added to the tube, finally secretory klotho (10 −8 to 10 −11 M) was added. Tube was centrifugated, and supernant was discarded. Beads were washed three times with PBS. Residual proteins on the beads were detected. Under anesthesia, rats were treated with PTH (100 miicro‐g/Kg) in the presence and absence of secretory klotho (10 micro‐g/Kg). Urinary c‐AMP was measured. Results Klotho, PTH receptor, antibody to PTH receptor were found as the remaining proteins on the beads. Klotho was detectable at 10 −9 M or more as the residual protein. Increases in urinary c‐AMP excretion by PTH were attenuated by the pretreatment with secretory klotho (3.0±0.5 vs 5.6±0.8 folds, p<0.05). Conclusion Secretory klotho binds to PTH receptors, inhibiting its signaling.