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10.3389/fpls.2019.01727 147 WhiteP

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In these participants, GH administration increased circulating phosphate levels by enhancing phosphate resorption, while IGF-1 treatment did not significantly modify phosphate concentrations.105 These effects of recombinant IGF-1 on bone remodeling and calcitriol production have been also observed in patients with GH deficiency, being more notable on osteoblast activity than in bone resorption.106 Furthermore, calcium influx from the bone store appears to be an important regulator of IGF-1 production, since patients with pycnodysostosis, who have a loss-of-function mutation of the Cathepsin K gene and develop osteosclerosis, show low levels of IGF-1, which may be associated with impaired osteoclastic activity.107 In addition, continuous infusion of PTH or PTH-related protein (PTHrP) increase circulating IGF-1 levels, along with plasma levels of calcium and calcitriol, as well as bone resorption.108 Of interest, the osteoanabolic effects of PTH are reduced in mice with IGF-1 knockout mice, as well as in osteoblasts derived from this mutant strain, while administration of exogenous recombinant IGF-1 increased in vitro proliferation.109 In contrast, total parathyroidectomy abolishes the effects of high dietary protein supplementation on the stimulation of renal and liver IGF-1 expression, as well as its actions on the compensatory kidney hypertrophy